Endocrines doi: 10.3390/endocrines7020023

Authors: André Priede Rodrigo Mariño Ivan Darby Phyllis Lau

Background/Objectives: The dental setting has been suggested as a location for opportunistic diabetes screenings. Diabetes screening is a pathway consisting of several steps that must be completed to reach a diagnosis. Previous research has found that most patients in the dental setting, when offered the opportunity to screen for diabetes, are willing to do so; however, amongst those who are referred for medical follow-up, there is low compliance. If diabetes screening in the dental setting is to be effective, strategies are required to maximise uptake and ensure completion of the screening pathway. Methods: This qualitative study examined participants in a diabetes screening trial held at dental clinics in Victoria, Australia. Semi-structured interviews were conducted by telephone, transcribed and analysed thematically. The themes identified were then deductively mapped onto the Capability, Opportunity, Motivation, Behaviour (COM-B) model and Theoretical Domains Framework (TDF). Results: Ten individuals who were screened for diabetes and referred to their general medical practitioner (GP) for a diabetes diagnosis were interviewed. The themes identified from the interviews were mapped to five COM-B domains: reflective motivation and automatic motivation, social and physical opportunity and psychological capability. These were linked to eight TDF domains associated with issues related to knowledge, environmental context and resources, memory, attention and decision processes, social influences, beliefs about consequences, emotions, and beliefs about capability. Conclusions: This study investigated the determinants influencing individuals’ decision to participate in diabetes screening and comply with referral advice. The results demonstrate the need to increase community knowledge around diabetes and screening for the condition, facilitate risk interpretation, and streamline the referral pathway between oral health professionals (OHP) and GPs. The study provides evidence that can be utilised for the development of future interventions that promote diabetes screening participation and maximise medical follow-up of referred individuals.

Endocrines doi: 10.3390/endocrines7020022

Authors: Filomena Mazzeo Gabriele Ferrara Fiorenzo Moscatelli Antonietta Monda Antonietta Messina Maria Ruberto Nicola Mancini Raffaele Ivan Cincione Gianluca Russo Salvatore Allocca Marco La Marra Pasquale Perrone Girolamo Di Maio Maria Casillo Giovanni Messina Mario Ruggiero Maria Giovanna Tafuri Vincenzo Monda

Background/Objectives: Regular physical exercise is strongly recommended for individuals with type 1 diabetes mellitus (T1DM) because of its beneficial effects on cardiovascular fitness, insulin sensitivity, metabolic control, and overall health. Nevertheless, participation in physical activity remains limited, largely due to the fear of exercise-induced hypoglycemia and glycemic instability. Glycemic responses to exercise in T1DM are influenced by the interaction between exercise modality, circulating insulin levels, nutritional status, and diabetes technologies. Continuous aerobic exercise, resistance training, high-intensity interval exercise, and mixed intermittent activities elicit distinct metabolic and hormonal responses, resulting in heterogeneous glycemic trajectories. This narrative review aimed to provide a clinically oriented synthesis of the physiological mechanisms underlying exercise-related glycemic fluctuations in T1DM and to discuss integrated insulin- and carbohydrate-based strategies to support safer participation in physical activity in the context of modern diabetes technologies. Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and complementary searches in Google Scholar to identify experimental studies, observational studies, systematic reviews, consensus statements, and clinical guidelines focused on exercise-related glycemic responses in individuals with T1DM. Only articles published in English were considered. Evidence was selected and synthesized according to relevance to exercise modality, insulin therapy strategies, carbohydrate management, and diabetes technologies, including continuous glucose monitoring, continuous subcutaneous insulin infusion, and automated insulin delivery systems. The final narrative synthesis was based on 44 selected studies, reviews, consensus statements, and guidance documents considered most relevant to the objectives of this narrative review. Results: Available evidence indicates that continuous moderate-intensity aerobic exercise is most consistently associated with progressive glucose declines and increased risk of hypoglycemia, particularly when performed in the presence of elevated insulin on board. In contrast, resistance exercise and short-duration high-intensity or anaerobic exercise more frequently induce stable glycemia or transient hyperglycemia through adrenergic stimulation and increased hepatic glucose output. Mixed and intermittent exercise modalities often produce more variable responses depending on exercise sequencing, nutritional status, and insulin exposure. Across studies, integrated adjustment of basal and prandial insulin doses together with individualized carbohydrate supplementation emerged as the most effective strategy to reduce exercise-related glycemic instability. Continuous glucose monitoring and insulin pump technologies improved glucose trend awareness and management flexibility; however, physical exercise remains a challenging condition for current automated insulin delivery algorithms and still requires active user-driven decision-making. Conclusions: Exercise management in T1DM should be based on an individualized interpretation of exercise modality, glucose trends, insulin exposure, and nutritional context rather than on fixed glucose thresholds alone. Combining anticipatory insulin adjustments, tailored carbohydrate strategies, and appropriate use of diabetes technologies may substantially reduce glycemic variability and improve confidence toward physical activity participation. Structured education and individualized clinical guidance remain essential to translate physiological knowledge into effective real-world exercise management.

Endocrines doi: 10.3390/endocrines7020021

Authors: Eduardo Federighi Baisi Chagas Nicole Simone de Lima Coelho Henrique Villa Chagas Maria Eduarda Costa Tâmega Sandra Maria Barbalho Jesselina Francisco dos Santos Haber

Background/Objectives: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition often managed exclusively with insulin. However, the search for adjuvant therapies has gained attention, including dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), despite limited evidence in pediatric populations. To evaluate the impact of DPP4i, alone or combined with SGLT2i, on glycemic control (HbA1c), lipid profile (ApoB and ApoA-I), and renal function (eGFR and albuminuria) in children, adolescents, and young adults with T1DM, this study was conducted. Methods: This cohort study analyzed data from 76 patients with T1DM aged under 25, followed for 4 to 20 months. Patients were grouped based on exposure to DPP4i alone, DPP4i + SGLT2i, or no additional therapy. Glycemic, lipid, and renal parameters were assessed at baseline and follow-up. Results: A significant reduction in HbA1c was observed in the overall sample (p < 0.001), regardless of treatment group, suggesting a positive effect of interdisciplinary care. There were no statistically significant differences in HbA1c variation among the groups. ApoB decreased significantly over time (p < 0.001), and ApoA-I levels were initially higher in the DPP4i + SGLT2i group. A significant reduction in albuminuria was identified in the DPP4i-only group compared to controls (p = 0.029), indicating a potential renoprotective effect. No significant changes in eGFR were observed. The use of DPP4i, with or without SGLT2i, was not associated with significant improvements in glycemic or lipid outcomes compared to standard therapy. However, DPP4i monotherapy was associated with a reduction in albuminuria, suggesting a possible benefit for renal protection. Conclusions: These findings highlight the need for larger, randomized studies to confirm the therapeutic role of these agents in young individuals with T1DM.

Endocrines doi: 10.3390/endocrines7020020

Authors: Anna Arecco Francesco Cocchiara Davide Carlo Maggi

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a prevalent condition with a significant annual incidence, particularly increasing with age. Its pathophysiology is explained by Virchow’s triad (venous stasis, vascular injury, and hypercoagulability). Tirzepatide, a dual receptor agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), is approved for type 2 diabetes mellitus (T2DM) and obesity, showing efficacy in lowering HbA1c and promoting weight loss. Recent case reports have linked tirzepatide to VTE events, particularly in patients experiencing significant weight loss, raising concerns about its safety profile. We present a case of a male T2DM subject who developed PE after five injections of tirzepatide in a patient with grade I obesity. We also review emerging literature on VTE associated with tirzepatide, emphasizing the need for further research to clarify the drug’s risk and underlying mechanisms.

Endocrines doi: 10.3390/endocrines7020019

Authors: Eleni C. Tzavela Betina Kandyla Chara Tzavara Irini-Ikbale Sakou Spyridon Karanasios Adamandini Plarinou Valerios Chatzianastasiou Dimitra Chatzisimonian Artemis Tsitsika Kyriaki Karavanaki

Objectives: Families play a pivotal role in the care of adolescents with chronic illnesses, such as type 1 diabetes (T1D). This study’s aim was to evaluate family functioning in families of adolescents with T1D and to assess its relationship with metabolic control. Methods: Fifty-eight adolescents and young adults diagnosed with T1D, aged 14–21 years, and 116 healthy adolescents (controls) matched for age, gender and socioeconomic status were included in this study. The participants’ mean age was 15.9 years (±1.6 years). The demographics and family functioning were reported by the participants. The McMaster Family Assessment Device (FAD) measured family functioning across six dimensions. Results: In problem-solving and behavioral involvement, T1D adolescents self-reported similar scores to healthy controls. On the contrary, in the domains of communication (p = 0.048), family roles (p = 0.045), affective responsiveness (p = 0.048), affective involvement (p = 0.043) and general functioning (p = 0.044), the T1D group scored lower than the controls, indicating better family functioning. Furthermore, within the T1D group, better metabolic control, assessed by glycated hemoglobin (HbA1c), was associated with a trend toward improved affective responsiveness, although this did not reach statistical significance (p = 0.091). Conclusions: Our findings highlight the importance of family functioning among adolescents with T1D and point toward distinct family processes that can be addressed in the context of routine care to enhance wellbeing and facilitate T1D management.

Endocrines doi: 10.3390/endocrines7020018

Authors: Jean-Luc Karavendzas Anna Galligan Melissa H. Lee Anthony Dowling Balasubramanian Krishnamurthy Richard J. MacIsaac

Objective: Current knowledge surrounding the diagnosis and mechanisms that result in immune checkpoint inhibitor-associated diabetes (ICI-DM) remain to be fully defined. We present clinical vignettes of patients that have presented to our hospital to illustrate the heterogenous clinical profiles that patients with ICI-DM can experience. We also provide an update on ICI-DM, focusing on current and future perspectives and emerging therapies. Methods: We performed a retrospective review of the electronic records of five ICI-DM patients who presented to St. Vincent’s Hospital Melbourne between 2020 and 2024, with patients identified from the hospital endocrinology and oncology databases. We also performed a literature review via a PubMed search using the keywords “checkpoint inhibitors” and “diabetes” between the years 2015 and 2025 to allow us to collate a descriptive review on ICI-DM. Results: Our cases show some heterogeneity in presentation, with biochemical evidence of diabetic ketoacidosis (DKA) in 4/5 patients, presentation 18–253 days (median 47 days) from ICI commencement, HbA1c 59–78 mmol/mol (median 66 mmol/mol), and c-peptide 0.06–0.77 pmol/mL (median 0.09 pmol/mL). Islet autoantibodies were present in 4/5 cases and high-risk HLA alleles identified in 1/2 tested patients. The findings from our descriptive review support a similar heterogeneity in ICI-DM presentations. Inconsistent diagnostic criteria for ICI-DM were noted with low c-peptide being the most common biochemical presentation. Pancreatic volume is emerging as a useful predictive marker of ICI-DM development. We found no reports of the reversal of ICI-DM with immunosuppression in humans, although recent preclinical studies suggest that this approach is feasible. Conclusions: Diagnostic criteria should include new-onset hyperglycaemia with low paired c-peptide, and may be supported with T1DM-associated autoantibodies and evidence of pancreatic atrophy on imaging. Further research is needed in the realm of predicting ICI-DM and considering the role of immunosuppression as a treatment modality.

Endocrines doi: 10.3390/endocrines7020017

Authors: Shuanhu Zhou Bonnie L. Padwa Julie Glowacki

Background/Objectives It is known that failure to gain sufficient bone during skeletal growth and maturation phases predisposes to the development of senile osteoporosis as age-related bone loss ensues. There is limited knowledge about factors that are necessary for the pubertal growth spurt and achievement of peak bone mass. Diminution or disappearance of Juvenile Protective Factors (JPFs) after a given maturational stage could contribute to the onset of age-related declines in a variety of physiological functions, including bone physiology. Methods With available pediatric platelet-poor plasma (PPP) and mesenchymal/skeletal stem cells (MSCs), we tested whether proteomics and RNA-seq methodology have potential for the discovery of novel regulators of pubertal skeletal growth. Results Our data demonstrate that pediatric PPP rejuvenates age-related compromised MSC functions; that Mass Spectrometry (MS)-based proteomics identified known and novel circulating tissue growth/trophic factors in human PPP of pubertal, as compared with pre-pubertal, and post-pubertal subjects; and that the unbiased RNA-Seq approach revealed new genes and networks of genes that are dramatically elevated or diminished in pubertal MSCs. Conclusions The findings support the hypothesis that the characterization of pro-osteogenic JPFs could lead to the identification of novel therapeutic approaches to promote bone health in the elderly and of potential treatment regimens for senile osteoporosis.

Endocrines doi: 10.3390/endocrines7020016

Authors: Nadhem Abdallah Nihar Kanta Jena Gisha Mohan Sreekant Avula

Background/Objectives: Patients with adrenal insufficiency (AI) are at an increased risk of adverse events (AEs) during cardiovascular hospitalization. However, the association between AI and takotsubo cardiomyopathy (TCM) remains unclear. We investigated the association between AI and cardiovascular outcomes in patients with TCM. Methods: We analyzed data on patients with TCM included in the 2019 Nationwide Readmissions Database to compare in-hospital outcomes between patients with and without AI. The primary outcome measure was inpatient mortality. Secondary outcomes included the odds of all-cause 90-day readmission, acute kidney injury (AKI), mechanical ventilation use, vasopressor use, cardiogenic shock, length of stay (LOS), and total hospitalization charges (THC). Multivariate regression models were used to adjust for confounding variables. Results: Among 30,987 cases, 0.59% (n = 183) had concomitant AI. AI was associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR] 3.32, 95% confidence interval [CI] 1.43–7.74, p = 0.005), cardiogenic shock (aOR 5.28, 95% CI 3.16–8.82, p < 0.001), mechanical ventilation use (aOR 3.20, 95% CI 1.78–5.74, p < 0.001), AKI (aOR 1.96, 95% CI 1.11–3.48, p = 0.021), vasopressor use (aOR 4.59, 95% CI 1.56–13.47, p = 0.006), longer LOS (6.84 vs. 3.67 days, p < 0.001), and higher THC ($97,419 vs. $54,574, p < 0.001). Additionally, AI was associated with lower odds of all-cause 90-day readmissions (aOR 0.44, 95% CI 0.25–0.79, p = 0.006). Conclusions: Among patients with TCM, AI was associated with higher odds of fatal and non-fatal adverse events. Further studies are required to confirm these findings and better understand how to improve outcomes in this high-risk population.

Endocrines doi: 10.3390/endocrines7020015

Authors: Trevor Tam Elaine Soong Louis Saada Anouk Borg Neil Dorward Francesca Swords Ketan Dhatariya Hani J. Marcus Rupa Ahluwalia

Introduction: Evidence on the use of dopamine agonists (DAs) for managing residual or recurrent non-functioning pituitary adenomas (NFPAs) is limited. We aim to evaluate the use of cabergoline (CAB) for NFPAs. Methods: A retrospective cohort study was conducted at a single UK centre, between November 2011 and December 2025. Twenty-six patients were identified. Ten patients were excluded due to CAB intolerance or discontinuation (n = 5), insufficient data (n = 4), or invalid scan due to patient movement (n = 1). The remaining 16 patients (mean age 68.9 ± 4 years (range 42–89 years old), 7/16 females) were included. CAB was initiated in cases where surgery or radiotherapy were not appropriate (e.g., due to age and/or comorbidities, or patient choice). Radiological response was assessed using at least two scans separated by a minimum interval of six months. Tumour shrinkage was defined as a reduction in volume of 20% or more, growth as an increase of 20% or more, and stabilisation as interval change of less than 20%. Results: Overall, tumour shrinkage was observed in 7/16 (43.8%) patients, stabilisation in the remaining 9/16 (56.3%) patients, over 503 ± 51 days (range of 117–934 days) (from the date of CAB initiation to latest MRI scan). There was a statistically significant reduction in tumour volume (p = 0.0335). In five patients with documented tumour growth prior to CAB initiation, growth rates retarded or reversed post-CAB initiation. Conclusions: Our findings in this small cohort potentially suggests that cabergoline can retard, arrest, or even reverse tumour growth in selected patients with NFPAs. Our review also highlights ongoing uncertainty regarding optimal dosing, approaches to dose up-titration, follow-up imaging intervals, and objective criteria for defining radiological response. Our results may provide a proof of concept for future, larger-scale prospective studies and controlled trials to validate the conclusions drawn.

Endocrines doi: 10.3390/endocrines7020014

Authors: Natasa Grulović Velimir Altabas Maja Baretić

Background: Although technology has improved the quality of diabetes management, it may also introduce subjective burdens and reveal barriers to its use. The primary aim of this research was to investigate the association between the use of advanced diabetes technology, such as continuous glucose monitoring, insulin pumps, mobile applications, and diabetes distress in adults with type 1 diabetes mellitus (T1DM). Methods: This multicenter, cross-sectional study conducted across Southeastern European countries included 499 adults with T1DM. All participants signed informed consent and completed the 20-item Problem Areas in Diabetes (PAID) Questionnaire. A total score of 40 or above was classified as high diabetes distress. Statistical analyses were performed using ANOVA, χ2 test, and logistic regression. Results: The mean age of participants was 49.11 ± 13.99 years, with a mean HbA1c value of 7.9 ± 1.46%. The mean PAID total score was 29.19 ± 19.51. High levels of diabetes distress were found in 28.86% of the participants. About 20% of participants used advanced diabetes technologies. Significant predictors of diabetes distress were gender, BMI, and HbA1c. After accounting for these predictors, advanced technology use was associated with a 42% lower likelihood of experiencing high levels of diabetes distress compared to those who used blood glucose meters. Conclusions: Diabetes distress remains a frequent issue among individuals with T1DM. However, patients using advanced diabetes technologies exhibited less distress. Our findings highlight the importance of a comprehensive approach to T1DM management that integrates technological advancements and psychosocial support.

Endocrines doi: 10.3390/endocrines7020013

Authors: Cinzia Aurilia Simone Donati Maria Luisa Brandi

Menin, the product of the Multiple Endocrine Neoplasia type 1 (MEN1) gene, is a scaffold protein, the lack of which leads to the development of a tumor syndrome primarily affecting endocrine organs. Although it is classified as an oncosuppressor, menin is a ubiquitous protein whose expression is also abundant in non-endocrine tissues such as the central nervous system, where knowledge of menin’s role still remains limited. In this article, we aim to draw attention to an underestimated clinical aspect of MEN1 syndrome, i.e., the psychological/psychiatric manifestations, in which menin deficiency could have an important function. Our aim is to highlight that a multidisciplinary team caring for patients with MEN1 throughout their lives should include professionals such as psychologists and psychiatrists in order to better manage any mental illness associated with the syndrome and to further improve the patient’s quality of life.

Endocrines doi: 10.3390/endocrines7010012

Authors: Ozlem Aydin Bulent Colakoglu Cavit Kerem Kayhan Mehmet Güven Günver Mariana Simplício Joana Pinto Schmitt Sule Canberk

Background: Risk stratification of indeterminate thyroid nodules (Bethesda III–IV) remains difficult and often triggers unnecessary procedures. Ultrasound-based ACR TI-RADS and the 2023 Bethesda System are widely used, but the incremental value of combining them and the role of size thresholds needs prospective validation. Objective: The objective of this study was to prospectively compare the diagnostic performance of ACR TI-RADS and the 2023 Bethesda System, alone and in combination, for predicting malignancy in thyroid nodules, with dedicated analyses of indeterminate lesions (Bethesda categories III–IV), including subtypes of Bethesda III (nuclear atypia vs. other atypia), and the impact of nodule size. Methods: Histopathology was available for 131 nodules. Diagnostic metrics (sensitivity, specificity, PPV, NPV), ROC curves (DeLong comparison), and Youden indices were calculated for individual and combined thresholds; a 16 mm size cut-off was explored. Results: Malignancy was confirmed in 105/131 nodules (80.2%). Bethesda outperformed TI-RADS (AUC 0.87 vs. 0.69; DeLong p = 0.041). Malignancy rates rose with higher categories (e.g., TI-RADS 5: 93.6%; Bethesda category V: 100%; Bethesda category VI: 100%) and were markedly elevated in the histologically confirmed subset for Bethesda category III (32/41; 78.0%) and IV (6/8; 75.0%). The combined requirement of TI-RADS ≥ 4 and Bethesda ≥ 4 maximized specificity (96.2%) and PPV (98.4%) with a high Youden J (0.552), supporting a rule-in strategy in category IV of Bethesda. Size alone was a weak discriminator (AUC 0.66); within Bethesda III–IV nodules, malignancy did not differ significantly by the 16 mm threshold (p = 1.00). ROC using continuous tumor size yielded AUC = 0.66; the ROC-derived optimal cut-off was 16 mm. Applying this split produced sensitivity 0.80 and specificity 0.50. Conclusions: Integrating ACR TI-RADS with Bethesda cytology significantly improves specificity and PPV for indeterminate thyroid nodules, supporting a morphology-driven approach over traditional size-based thresholds. Incorporation of combined sonographic–cytologic criteria into management algorithms may reduce unnecessary interventions and optimize patient care.

Endocrines doi: 10.3390/endocrines7010011

Authors: Stefano Iuliano Roberta Misiti Marta Greco Francesco S. Brunetti Vincenzo Aiello Antonio Brunetti Maria Mirabelli Daniela P. Foti

Background/Objectives: The aim of this study is to describe sex- and age-specific patterns of HbA1c in adults with type 2 diabetes (T2D) mellitus across three temporal cohorts from Southern Italy (2012, 2017, and 2024), and to assess whether glycemic differences between men and women persist, narrow, or evolve over time. Methods: We analyzed three independent cohorts of adults with T2D, including 1249 patients in 2012 and 1125 patients in both 2017 and 2024. HbA1c values were summarized as medians and interquartile ranges within sex- and age-stratified groups. Temporal variation in cohort-specific median HbA1c was examined across timepoints within each sex and age category, and sex differences were assessed within each cohort year. Results: At the population level, median HbA1c values remained within a narrow range across all three cohorts, indicating overall temporal stability of glycemic control. No significant sex differences were observed in 2012 or 2024, and only one age stratum (≥80 years) showed a significant sex difference in 2017, with men exhibiting slightly higher median HbA1c. Age-stratified analyses revealed heterogeneous temporal patterns. In older adults (≥70 years), HbA1c medians were remarkably stable in both sexes (approximately 7.2–7.4% in women and 7.2–7.6% in men). In midlife (40–59 years), women tended to show modest increases or partial reversals in HbA1c, whereas men displayed worsening between 2012 and 2017 followed by stabilization thereafter. The youngest adults (18–29 and 30–39 years) showed the highest HbA1c levels in 2017 and the largest subsequent improvements between 2017 and 2024 in both sexes, with median values decreasing toward approximately 7.1–7.6%. Conclusions: Despite well-described biological and social sex differences in T2D, median HbA1c values in this real-world setting were broadly comparable between men and women and largely stable over a 12-year period. Sex differences were small, inconsistent, and age-dependent, with age, and not sex, emerging as the primary determinant of HbA1c over time. These findings suggest that sex-related disparities in glycemic control may be better understood through a dynamic, life-course perspective rather than static cross-sectional comparisons.

Endocrines doi: 10.3390/endocrines7010010

Authors: Christian Battipaglia Alessandro D. Genazzani Valeria Vescovi Peter Chedraui Rossella E. Nappi

Background/Objectives: Migraine is a leading cause of disability in women and is intricately linked to hormonal fluctuations and systemic health. This review aims to unravel the complex relationship between migraine, cardiovascular disease, and metabolic syndrome throughout the female reproductive lifespan. Methods: A comprehensive narrative review was conducted using the PubMed database for studies published between January 1988 and December 2025. Keywords included “migraine”, “cardiovascular risk”, “metabolic syndrome”, “pregnancy”, and “hormonal therapy”. Articles were selected to synthesize the latest pathophysiological evidence and clinical guidelines. Results: Migraine prevalence in women is two to threefold higher than in men, peaking during fertile age. Hormonal milestones, particularly estrogen withdrawal, trigger menstrual migraine. Metabolic syndrome is significantly more common in migraineurs than the general population. Obesity and insulin resistance have been associated with higher migraine attack frequency and severity. Experimental evidence suggests that hyperinsulinemia may sensitize TRPV1 receptors on trigeminal neurons and enhance CGRP release, potentially lowering the activation threshold for migraine attacks; however, direct confirmation of this pathway in humans remains limited. Furthermore, migraine with aura is linked to a doubled risk of ischemic stroke and increased risk of cardiovascular events. In pregnancy, migraine is an independent risk factor for stroke, myocardial infarction, and spontaneous coronary artery dissection. Conclusions: Migraine is a critical marker for cardiovascular and metabolic risk, necessitating routine screening and multidisciplinary management. Clinicians must prioritize cardiovascular counselling, metabolic evaluations, and careful monitoring in these patients, especially during pregnancy. Hormonal therapy choices should be individualized, preferring progestin-only contraceptives for those with aura and transdermal routes for hormone replacement therapy to minimize cardiometabolic impact.

Endocrines doi: 10.3390/endocrines7010009

Authors: Gianmarco Adinolfi Valeria Milia Boris Dinkov Galya Stavreva

Background: Cardiovascular complications are a leading cause of death in patients with type 2 diabetes (T2D). The GLP-1 receptor agonist (GLP-1RA) semaglutide has shown cardiometabolic benefits in individual studies, but a comprehensive analysis of its effects in both oral and subcutaneous formulations is lacking. Objective: This study aimed to systematically evaluate the impact of semaglutide, in oral and subcutaneous formulations, on major adverse cardiovascular events (MACE) in patients with T2D. Methods: This review adhered to the PRISMA guidelines and included a comprehensive search of PubMed, MEDLINE, and Google Scholar from November 2016 to June 2025. High-quality randomized controlled trials (RCTs) comparing semaglutide with placebo in patients with T2D were included. The primary endpoint was MACE, defined as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Hazard ratio (HR) and 95% confidence intervals (CIs) were pooled using a random-effects model. Results: Of the 127 articles screened, 3 trials involving 16,130 participants met the inclusion criteria. The pooled HR for MACE across the SOUL, SUSTAIN-6, and PIONEER-6 trials was 0.83 (95% CI: 0.76–0.92; I2 = 25%), indicating a 17% relative risk reduction with low heterogeneity. Adverse event profiles were comparable between the semaglutide and placebo groups. Conclusions: Semaglutide use was associated with a significant and consistent reduction in MACE in patients with T2D, supporting its role as a valuable therapeutic option for combined glycemic control and cardiovascular risk reduction.

Endocrines doi: 10.3390/endocrines7010008

Authors: Antonio Maria Labate Lorenzo Moretti Provvidenza Villari

Background: Older patients with type 2 diabetes mellitus (T2DM) are often undertreated because of concerns regarding hypoglycaemia and clinical heterogeneity. Although the evidence base for oral semaglutide is growing, data specifically in older adults remain relatively limited, particularly regarding long-term effectiveness and tolerability in routine practice. Methods: This observational study included 81 patients aged ≥65 years with T2DM treated with oral semaglutide for 12 months. Changes in glycaemic, anthropometric and cardiometabolic parameters were evaluated. The primary endpoint was the achievement of HbA1c < 7% at 12 months. Multivariable logistic regression was performed to identify baseline predictors of response. Results: HbA1c decreased from 7.75 ± 1.01% to 6.80 ± 0.88% after 12 months (p < 0.00001). Significant reductions were observed in body weight (−4.09 ± 4.42 kg, p < 0.00001), BMI (−1.50 ± 1.55 kg/m2, p < 0.00001) and waist circumference (−5.83 ± 4.71 cm, p < 0.00001). Improvements were also detected in lipid profile, blood pressure and visceral adiposity indices. No hypoglycaemic events were reported during follow-up. In multivariable analysis, baseline age, diabetes duration, baseline HbA1c and baseline VAI were not independently associated with the achievement of HbA1c < 7%; therefore, these baseline factors did not discriminate responders within our cohort (hypothesis-generating). Greater absolute HbA1c reductions were observed in patients with higher baseline HbA1c. Conclusions: In older patients with T2DM, oral semaglutide is associated with effective glycaemic control without hypoglycaemia and with a response largely independent of baseline clinical characteristics, supporting its use in elderly and clinically heterogeneous populations.

Endocrines doi: 10.3390/endocrines7010007

Authors: Maria Savvidou Ioanna Tsatsou Polixeni Liamopoulou Paraskevi-Maria Prapa Maria Lavdaniti

Background/Objectives: The co-existence of Type 2 Diabetes Mellitus (T2DM) and cancer presents complex self-management challenges due to competing health demands. This study aimed to evaluate and compare self-care activities and adherence to medical recommendations between T2DM patients with cancer and a non-cancer T2DM control group. Additionally, it investigated the impact of sociodemographic and clinical characteristics on treatment adherence. Methods: A cross-sectional study was conducted in a general hospital in Thessaloniki, Greece, using convenience sampling. The sample consisted of 62 participants: 29 patients with T2DM and cancer and 33 controls with T2DM only. Data were collected using the “Diabetes Self-Care Activities Questionnaire”, analyzing subscales for self-care activities and adherence to medical orders. Results: The cancer group was notably older, with a mean age of 69.8 years compared to 60.3 years in the control group (p < 0.001). While overall adherence scores were comparable between groups, significant disparities existed in specific domains. The cancer group demonstrated a critical neglect of foot care recommendations compared to controls (p < 0.001), with a very large effect size (d = 1.60). Conversely, cancer patients reported significantly stricter adherence to dietary recommendations (p = 0.001, d = 0.96). Within the cancer group, older age and lower education were unexpectedly associated with better foot care adherence (p < 0.05). Conclusions: The results suggest a distinct prioritization among cancer patients, whereby they reported maintaining strict dietary adherence while potentially deprioritizing preventative foot care. Clinical practice should consider transitioning to an integrated model where oncology healthcare professionals actively reinforce diabetic foot surveillance to prevent complications.

Endocrines doi: 10.3390/endocrines7010006

Authors: Nicolas Zucchini Francesca Lo Celso Alice Gabrieli Clemente Junior Nappi Nicolò Bortolussi Silvia Palmisano Chiara Dobrinja Giovanni Fantola

Background: The interplay between obesity and thyroid dysfunction is complex, characterized by adaptive hyperthyrotropinemia and peripheral hormone resistance. Metabolic and Bariatric surgery (MBS) has emerged not only as a weight-loss (WL) intervention but also as a potent modulator of the thyroid–gut axis. Methods: We conducted a narrative review of the literature (2015–2025), synthesizing data from prospective cohorts, meta-analyses, and mechanistic studies to evaluate the impact of MBS on thyroid function, autoimmune dynamics, and drug pharmacokinetics. Discussion: Current evidence suggests that MBS promotes a recalibration of the thyroid axis. Post-operative WL is independently associated with a significant reduction in serum thyroid-stimulating hormone (TSH) and free triiodothyronine (fT3) levels, reversing obesity-induced peripheral resistance. Concurrently, the reduction in systemic inflammation (NOD-like receptor protein 3 (NLRP3) inflammasome deactivation) may dampen lymphocytic infiltration, while the amelioration of gut dysbiosis and intestinal permeability is hypothesized to reduce cross-reactivity mechanisms (molecular mimicry), leading to decreased antibody titers in Hashimoto’s thyroiditis. However, these benefits are counterbalanced by altered drug absorption mechanisms. While most hypothyroid patients benefit from reduced Levothyroxine (L-T4) requirements due to decreased lean mass, malabsorptive procedures (Roux-en-Y Gastric Bypass, One Anastomosis Gastric Bypass) can precipitate refractory hypothyroidism due to bypassed absorptive surfaces and altered gastric pH. Conclusions: MBS offers a dual benefit of functional restoration and modulation of autoimmune markers. However, post-surgical management requires a tailored approach. Clinicians must distinguish between the physiological decline in TSH (adaptive) and iatrogenic malabsorption, advocating for liquid L-T4 formulations in complex malabsorptive phenotypes.

Endocrines doi: 10.3390/endocrines7010005

Authors: Mariam S. Alharbi

Objectives: This study aimed to evaluate adherence to therapy in hypoparathyroidism and related endocrine–metabolic disorders and to assess its association with biochemical outcomes, hypocalcemia episodes, and health-related quality of life (HRQoL). Methods: In accordance with PRISMA 2020 guidelines, PubMed, Scopus, Google Scholar, and the Cochrane Library were searched until September 2025. The eligible studies were randomized controlled trials, cohort, case–control studies, cross-sectional, and observational studies that reported adherence to calcium/vitamin D or recombinant parathyroid hormone therapy. Results: twenty-three studies were included in the qualitative synthesis, and 11 studies were included in the quantitative meta-analysis. Pooled medication adherence compliance was 70–82% and improved with simplified regimens and the use of recombinant PTH. Additionally, this was also associated with an improvement in HRQoL (p < 0.0001) and a lower risk of hypocalcemia (p < 0.0001). Conversely, multifactorial regulation was observed as the level of adherence had no significant effect on serum calcium levels (p = 0.7116). Sensitivity analyses demonstrate the strength of findings and indicate no significant publication bias. Conclusions: Medication adherence is a key factor in determining patient-centered outcomes in hypoparathyroidism. Better adherence is linked to a higher quality of life and fewer episodes of hypocalcemia, while its effect on biochemical parameters seems minimal. Educational programs, simple treatment regimens, and wider access to rhPTH therapy can be used to improve patient management of the disease over time.

Endocrines doi: 10.3390/endocrines7010004

Authors: Luca Galassi Erica Altamura Elena Goldoni Gabriele Carioti Beatrice Faitelli Matteo Lino Ravini Niccolò Le Donne Kristi Nika

Diabetic foot complications represent a major global health burden and arise from a multifactorial interaction between neuropathy, ischemia, infection, and impaired wound repair. Increasing evidence suggests that, beyond traditional vascular and metabolic risk factors, endocrine dysregulation plays a central role in shaping vascular dysfunction and tissue vulnerability in patients with diabetes. This narrative review provides an updated overview of the endocrine–vascular axis in the development, progression, and healing of diabetic foot ulcers (DFUs), integrating evidence from experimental and clinical studies identified through targeted searches of PubMed, Embase, and Scopus. We examine how alterations in insulin signaling, relative glucagon excess, adipokine imbalance, dysregulation of stress hormones, and thyroid dysfunction interact with chronic hyperglycemia, dyslipidemia, mitochondrial dysfunction, and low-grade inflammation to impair endothelial homeostasis. These disturbances promote oxidative stress, reduce nitric oxide bioavailability, and compromise microvascular perfusion, thereby creating a pro-ischemic and pro-inflammatory tissue environment that limits angiogenesis, extracellular matrix (ECM) remodeling, immune coordination, and effective wound repair. By linking pathophysiological mechanisms to clinical relevance, this review highlights potential biomarkers of endocrine–vascular dysfunction, implications for risk stratification, and emerging therapeutic perspectives targeting metabolic optimization, endothelial protection, and hormonal modulation. Finally, key knowledge gaps and priority areas for future translational and clinical research are discussed, supporting the development of integrated endocrine-based strategies aimed at improving DFU prevention, healing outcomes, and long-term limb preservation in patients with diabetes.

Endocrines doi: 10.3390/endocrines7010003

Authors: Antonio Brunetti

Endocrines was launched five years ago with a clear goal: to offer an open, rigorous, and inclusive forum for research spanning basic, translational, and clinical endocrinology and metabolism [...]

Endocrines doi: 10.3390/endocrines7010002

Authors: Elabbass A. Abdelmahmuod Mohamad Abufaied Shehab F. Mohamed Nada Elharabi Ahmed Elmudathir Osman Rafal Al-Shibly Raghad Bataineh Maab F. Elhaj Dabia Al-Mohanadi Mohammed Bashir Tania Jaber

Background: Papillary thyroid cancer (PTC) incidence is rising, particularly among Adolescents and Young Adults (AYA, 15–39 years). However, data on PTC characteristics in the AYA population, especially from the Middle East, remain limited. This study aims to describe the clinicopathological features of PTC in AYA patients treated at a large tertiary center in Qatar. Methods: A retrospective chart review was conducted for AYA patients diagnosed with PTC between May 2015 and December 2020 at Hamad General Hospital, Qatar. Data on demographics, tumor characteristics, histopathology, staging, risk stratification, and treatment were extracted and analyzed. We stratified the cohort based on sex. Results: We studied 326 AYA patients (mean age 33.0 ± 5.2 years); the majority were females (72.7%) and were mostly of Asian origin (51.5%). Most patients underwent total thyroidectomy (77.6%), while 22.4% underwent partial thyroidectomy. Histologically, classic PTC was most common (83.38%), followed by the follicular variant (16.00%). Capsule invasion occurred in 21.04%, vascular invasion in 11.76%, and lymphatic invasion in 14.38%. Most patients were at low ATA risk (68.61%), with intermediate (20.06%) and high risk (11.33%) less common. Distant metastases were rare (0.3%), and 59.1% received Radioactive iodine (RAI). Compared to females, males had larger tumors (mean 2.65 cm vs. 2.01 cm, p = 0.0009), higher rates of vascular invasion (22.4% vs. 7.7%, p < 0.001), affected lymph nodes (mean 4.2 vs. 2.4, p = 0.0223), and ATA high-risk proportions (23.5% vs. 7.0%, p < 0.001). Conclusions: This study provides the first detailed characterization of PTC in AYA patients from Qatar. While confirming female predominance, males exhibited more aggressive features (larger tumors, higher LN involvement, and ATA risk). These findings emphasize the need to consider gender-specific differences in managing PTC within the AYA population.

Endocrines doi: 10.3390/endocrines7010001

Authors: Phillip J. Gauronskas Terrie J. Lynch Eugene D. Albrecht Gerald J. Pepe

Introduction: We previously showed that baboon offspring born to mothers deprived of estrogen during the second half of gestation exhibited insulin resistance prior to and after the onset of puberty. Moreover, the size of skeletal muscle myofibers and the number of microvessels important for delivery of insulin/glucose to myofibers were lower in near-term fetuses deprived of estrogen during pregnancy, and myofiber capillarization remained reduced in post-pubertal offspring deprived of estrogen in utero. However, it remains to be determined whether skeletal muscle size is restored to normal in animals deprived of estrogen in utero after the onset of puberty/gonadal estrogen production. Methods: To answer this question, the current study quantified the size and number of slow and fast fibers in biopsies of vastus lateralis skeletal muscle obtained from post-pubertal female baboon offspring 9–12 years old, born to mothers who were untreated (n = 7) or treated during the second half of gestation with letrozole (n = 6; suppressed maternal and fetal estrogen by >90%) or letrozole plus estradiol benzoate (n = 3). Results: Results indicated that skeletal muscle slow and fast fiber growth in female offspring appeared to occur by hypertrophy and that respective size of fibers after the onset of puberty was similar in offspring born to mothers who were untreated or deprived of estrogen in utero. Conclusions: Postnatal myofiber hypertrophy likely reflects the impact of the pubertal surge in and continued exposure of offspring myofibers to ovarian estrogen and is restored to normal in post-pubertal female offspring deprived of estrogen in utero.

Endocrines doi: 10.3390/endocrines6040056

Authors: Olesea Scrinic Eduard Circo Seila Musledin

Background/Objectives: Thyroid dysfunction during pregnancy is associated with a range of adverse perinatal outcomes. This study aims to evaluate the effect of maternal thyroid autoimmunity on selected gestational and perinatal outcomes of the newborn in a region with adequate iodine intake. Methods: This retrospective study included 74 full-term singleton pregnancies from women living in the coastal region of Romania. Participants were divided into two groups: group 1—women with chronic autoimmune thyroiditis and euthyroidism; group 2—women without thyroid disorders, serving as the control group. Maternal variables assessed included serum thyroid hormone levels and antithyroid autoantibodies. For newborns, parameters such as birth weight, neonatal TSH levels, and the incidence of gestational and perinatal events were evaluated. Results: The incidence of chronic autoimmune thyroiditis in the study population was 36.4%. Maternal thyroid autoimmunity was associated with an increased incidence of low birth weight, observed in 11% of the autoimmune group compared with 2.1% in the control group (p = 0.099). The incidence of preterm birth was significantly higher in the autoimmune group (18.5% vs. 4.2% in controls, p = 0.043), corresponding to a 4.3-fold increase in relative risk. The most frequent perinatal complication observed in pregnant women with thyroid autoimmunity was spontaneous abortion (11.1%). The median urinary iodine concentrations were within the adequate range in both study groups. Conclusions: Thyroid autoimmunity during pregnancy presents significant clinical challenges, even in areas with adequate iodine intake. Maternal autoimmune thyroiditis constitutes an established risk factor for impaired fetal development and adverse perinatal outcomes. Early assessment of thyroid function prior to conception or during the first trimester is recommended for both diagnostic and preventive purposes.

Endocrines doi: 10.3390/endocrines6040055

Authors: Josivan Gomes Lima Lucas Nobrega Lima Vitor Yan Bezerra Araujo Lucia Helena Coelho Nobrega Julliane Tamara Araújo de Melo Campos

Generalized lipodystrophies (GLs) are rare diseases characterized by a lack of body fat. When patients with a GL phenotype are referred with a presumptive diagnosis of congenital generalized lipodystrophy (CGL) but genetic testing for known pathogenic variants is negative, the diagnosis of acquired generalized lipodystrophy (AGL) becomes a more likely diagnosis. No single test confirms such a diagnosis, and it is crucial to recognize the similarities and differences between these diseases. We review the literature and report four GL cases from our lipodystrophy outpatient clinic, highlighting the main points for an accurate diagnosis. Similarities: phlebomegaly, umbilical scar protrusion, loss of Bichat’s fat pad, muscle hypertrophy, and hepatomegaly can occur in both. Cirrhosis can also arise, but in AGL, it occurs as a consequence of hepatic steatosis and also due to autoimmune hepatitis. Insulin resistance is frequent, and patients present acanthosis nigricans and acrochordons and may develop difficult-to-control diabetes and its complications, despite very high daily doses of insulin. Low HDL and hypertriglyceridemia are frequent and may progress to acute pancreatitis. Serum leptin levels are typically low and contribute to hyperphagia. Differences: AGL patients’ body fat loss occurs gradually in childhood or adolescence, whereas CGL patients are born with the characteristic phenotype. Evaluating photographs of AGL patients in the first years of life can provide evidence of this selective and gradual fat loss. Some AGL patients may have panniculitis (inflamed and painful subcutaneous nodules), with or without autoimmune diseases. In conclusion, recognizing both similarities and differences is crucial for making an accurate diagnosis and ensuring the most appropriate treatment.

Endocrines doi: 10.3390/endocrines6040054

Authors: Nida Jugulytė Daiva Bartkevičienė

For many years, menopause-related bone loss has been attributed solely to declining estrogen levels. Recently it has been suggested that bone loss accelerates during perimenopause, often preceding declines in estradiol (E2), proposing that follicle-stimulating hormone (FSH), the levels of which are high during late perimenopause, may play a role in skeletal deterioration independently of E2. The aim of this narrative review was to present aspects of bone health throughout the menopause transition with a focus on the relationship between FSH and bone-related outcomes. Epidemiological studies evaluating bone mineral density (BMD) and bone turnover markers (BTMs) were analyzed. Higher FSH levels were associated with reduced BMD, particularly at the spine and hip, as well as enhanced bone remodeling activity. In several longitudinal studies, FSH was found to be a more reliable predictor of bone loss than estrogen. In conclusion, FSH may serve as an early marker of perimenopausal bone health deterioration by identifying women at risk for bone loss and allowing for more personalized prevention strategies; however, further research is needed before its clinical use.

Endocrines doi: 10.3390/endocrines6040053

Authors: Dody Houston Billhaq Seunghyung Lee

The ovarian corpus luteum has functional mechanisms for formation and regression in the reproductive endocrine system. The main functional events of the corpus luteum are angiogenesis and apoptosis mechanisms. The development of the corpus luteum involves homogeneous physiological mechanisms, including cellular functions and reproductive hormones. Angiogenesis is controlled by pro-angiogenic and anti-angiogenic factors. The microenvironment involves various signaling molecules and pathways that may play a potential role in angiogenic response during corpus luteum growth. In luteolysis, the corpus luteum undergoes degeneration, notably induced by reproductive hormones that promote programmed cell death in luteal cells through the apoptosis mechanism. In this sudy, we discuss the mechanisms and functional roles of angiogenesis and apoptosis in the endocrine microenvironment during corpus luteum formation and regression, based on the interrelationship of physiological events in the ovary.

Endocrines doi: 10.3390/endocrines6040052

Authors: Filipe Dias de Souza Patrícia Medici Dualib Martha Camillo Jordão Micaela Frasson Montero Maria Carolina Oliveira Abate Leonardo Luna Rosiane Mattar Bianca de Almeida-Pititto

Background/Objectives: The association between gestational weight gain (GWG) and adverse outcomes in individuals with gestational diabetes mellitus (GDM) and obesity remains unclear. This study aimed to evaluate the relationship between total GWG and maternal, obstetric, and neonatal outcomes in patients with GDM, stratified by obesity class. Methods: This retrospective cohort included 695 pregnant individuals with GDM treated at a tertiary university hospital in Brazil between 2007 and 2021. GWG was categorized as insufficient, adequate, or excessive per National Academy of Medicine guidelines. Outcomes included maternal, obstetric, and neonatal events. Analyses were conducted for the entire cohort and stratified by obesity class (I and II/III), using multivariate regression models adjusted for maternal age, parity, and pre-pregnancy BMI. Results: The mean age was 33.6 (SD 5.7) years. GWG was insufficient in 33.2%, adequate in 28.2%, and excessive in 37.8%. Excessive GWG was associated with increased odds of cesarean delivery (OR 1.69; 95% CI 1.15–2.48) and large-for-gestational-age newborns (OR 3.29; 95% CI 1.61–6.46). As a continuous variable, GWG was positively associated with cesarean delivery (OR 1.04), LGA (OR 1.10), and birthweight (β = 0.02). Lower GWG was independently associated with reduced preeclampsia risk (OR 1.09 per kg). Insufficient GWG was not linked to increased risk of small-for-gestational-age newborns or other adverse outcomes and was associated with lower insulin requirement. Results remained consistent across obesity subgroups, except for cesarean delivery in class II/III obesity. Conclusions: In individuals with GDM and obesity, insufficient GWG was not associated with increased adverse outcomes, while excessive GWG was consistently linked to unfavorable maternal and neonatal risks. Stricter GWG control may be safe and beneficial in this population.

Endocrines doi: 10.3390/endocrines6040051

Authors: Tanyara Baliani Payolla Paula Nascimento Brandão-Lima Gabrielli Barbosa de Carvalho Flávia Mori Sarti Regina Mara Fisberg Marcelo Macedo Rogero

Background/Objectives: Insulin resistance (IR) in adolescents contributes to the development of metabolic and immunological alterations. These alterations can lead to chronic, systemic, low-grade inflammation in adulthood. Evidence suggests that alterations in miRNA expression play a significant role in the onset of IR by influencing insulin signaling pathways. Therefore, identifying specific miRNAs may aid in the early diagnosis of cardiometabolic risk, particularly during the transition from adolescence to adulthood. Methods: This population-based study aimed to analyze the expression of 21 miRNAs in the plasma of adolescents. We considered IR status, overweight, sex, and age for the analyses. The study measured miRNA expression in plasma samples from 187 adolescents aged 12 to 19 years from the cross-sectional study of the 2015 São Paulo Health Survey (ISA-Nutrition). MiRNA expression was assessed using Exiqon® assays on Fluidigm® technology (Les Ulis, France). Statistical analyses were performed to identify differences in miRNA expression and correlations between variables, using a complex research design to ensure representativeness at the population level. Results: The incidence of IR and overweight was high in adolescents (44% and 33%, respectively). High-sensitivity C-reactive protein (hs-CRP) concentration was higher in overweight adolescents. IR was correlated with higher plasma expression of miR-122 and miR-139-3p. Furthermore, miR-486, miR-363, miR-30d, miR-28, miR-223, miR-21, miR-146, miR-130b, miR-126, miR-122, and miR-139-3p showed specific correlations with individual risk for IR, sex, and adolescent stage. Conclusions: The miRNAs showed differential expression according to sex and adolescent stage, and were correlated with cardiometabolic risk factors, suggesting their potential utility for early screening in adolescents. The study highlights age- and sex-related differences in miRNA levels between adolescents with IR and overweight. The cross-sectional design is a limitation of this study, as we cannot infer causality for the associations observed here.

Endocrines doi: 10.3390/endocrines6040050

Authors: Stefania Giuliano Giuseppe Seminara Stefano Iuliano Stefania Obiso Eusebio Chiefari Daniela P. Foti Maria Mirabelli Antonio Brunetti

Background: Obesity has been proposed as a risk factor for differentiated thyroid carcinoma (DTC), though findings in the literature remain conflicting. While some studies suggest an association between elevated body mass index (BMI) and thyroid malignancy, others attribute this link to diagnostic bias. The Calabria region in Southern Italy, historically affected by iodine deficiency and endemic goiter, offers a valuable population for investigating this relationship. Objective: This study aimed to evaluate the association between obesity and clinical, sonographic, and cytological characteristics of thyroid nodules in a Calabrian cohort undergoing fine-needle aspiration biopsy (FNAB). Methods: This retrospective observational study included 1192 patients evaluated at a single endocrine referral center between 2015 and 2024. Patients were stratified by BMI (<30 vs. ≥30 kg/m2). Demographic, biochemical, ultrasound, and cytological data were collected and analyzed. Cytological results were classified according to the SIAPEC 2014 system. Results: Obese patients had significantly larger thyroid nodules in terms of anteroposterior and transverse diameters, as well as overall volume (p < 0.05). However, the distribution of high-risk cytological categories (TIR 3B, TIR 4, and TIR 5) did not differ significantly between obese and non-obese patients (9.4% in both groups). Multivariate analysis confirmed that BMI was not an independent predictor of malignancy risk (OR 0.988; p = 0.723), whereas younger age was inversely associated with malignancy. Conclusions: Obesity appears to influence thyroid nodule size but does not constitute an independent risk factor for cytological malignancy. BMI should not influence indications for FNAB or subsequent treatment decisions. Thyroid nodule management should instead rely on ultrasound risk stratification and cytological findings. Special attention should be given to younger patients as they may carry a higher malignancy risk.

Endocrines doi: 10.3390/endocrines6040049

Authors: Margarida C. Pinheiro Henrique E. Costa Melissa Mariana Elisa Cairrao

Background/Objectives: Adequate sleep has a fundamental role in human health, mainly in cognitive and physiological functions. However, the daily demands of modern society have led to a constant pursuit of better living conditions, requiring more active hours at the expense of sleeping hours. This sleep deprivation has been associated with human health deterioration, namely an increase in Diabetes Mellitus incidence. This metabolic disease is a chronic pathology that imposes a big burden on health systems and is associated with the rise in insulin resistance. In this sense, the aim of this review is to analyze the relation between sleep deprivation and insulin resistance, emphasizing the metabolic parameters and hormones that may be involved in the subjacent mechanism. Methods: A literature review of the last 10 years was performed with specific terms related to “sleep deprivation” and “insulin resistance”. Results: Overall, the studies analyzed showed a decrease in insulin sensitivity in cases of sleep deprivation, even with different study protocols. In addition, an association between sleep deprivation and increased non-esterified fatty acids was also noticeable; however, other parameters such as cortisol, metanephrines, and normetanephrines showed no consistent results among the studies. Conclusions: This review allowed us to confirm the relationship between sleep deprivation and insulin resistance; however, despite the difficulties to monitor sleep, more research is needed to understand the related mechanisms that have not yet been clarified.

Endocrines doi: 10.3390/endocrines6030048

Authors: Tanvir Ahmed Jaimala Kishore Mensila Onamika Shuvratithi Goswami Iffat Rahman Momo Hanif Sumon Rodney G. Bowden

Background: The oral glucose tolerance test (OGTT) is the gold standard for diagnosing diabetes; however, its use is often limited by the need for laboratory infrastructure, trained personnel, and extended turnaround times. In contrast, glucometer-based OGTT offers a convenient and affordable alternative, especially in resource-limited settings. Objective: This narrative review aims to assess the diagnostic accuracy of glucometer-based OGTT compared to standard laboratory-based OGTT, while also evaluating its feasibility and potential application in diabetes screening programs. Evidence Summary: Studies consistently demonstrate a strong correlation between capillary glucose levels measured by glucometers and venous plasma glucose concentrations obtained through standard laboratory methods. Many studies reported high sensitivity and specificity, often exceeding 90%, particularly when using well-calibrated, newer-generation devices. These findings support the diagnostic utility of glucometer-based OGTT in various populations, although performance may vary by device model and clinical context. Standardization of testing protocols remains essential for consistent results. Conclusions: Glucometer-based OGTT shows promise as a reliable, rapid and cost-effective diagnostic approach, particularly in low-resource and community-based settings. While it is not a complete substitute for laboratory-based OGTT, it offers substantial advantages in accessibility, affordability, and scalability. Continued research with newer-generation glucometers and standardized testing protocols is essential to support broader clinical implementation and public health integration.

Endocrines doi: 10.3390/endocrines6030047

Authors: Jose Jorge Ortez Toro

The intersection of type 2 diabetes mellitus (T2DM) and sarcopenia, often termed diabetic sarcopenia, represents a critical yet underrecognized comorbidity that significantly impacts the quality of life and functional capacity of older adults. This paper explores the complex interplay between T2DM and sarcopenia, focusing on the prevalence, risk factors, and underlying mechanisms driving muscle mass and strength decline in this population. Drawing from recent clinical studies, we highlight a prevalence of sarcopenia ranging from 15.36% to 30.2% among elderly T2DM patients, with notable gender disparities (41.3% in men versus 20.1% in women) and regional variations. Key risk factors identified include poor glycemic control (HbA1c ≥8%), longer diabetes duration (>5 years), low body mass index (BMI), and reduced levels of 25-hydroxyvitamin D and insulin-like growth factor-1 (IGF-1). We also recommend a practical screening algorithm for diabetic sarcopenia, integrating tools like the SARC-F questionnaire, dynamometry, and BMI-adjusted calf circumference to facilitate early diagnosis and staging in clinical settings. The review underscores the need for a multidisciplinary approach—encompassing pharmacological optimization, nutritional interventions with high-protein diets, and tailored physical exercise—to mitigate muscle loss and improve metabolic outcomes. Future research directions should focus on validating diagnostic protocols and diagnosis techniques and further exploring specific therapies to effectively address this dual burden.

Endocrines doi: 10.3390/endocrines6030046

Authors: Fernando Sebastian-Valles Álvaro Montes Muñiz Mónica Marazuela

Remnant cholesterol, contained within triglyceride-rich lipoproteins such as VLDL and IDL, has emerged as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in both the general population and individuals with diabetes. Unlike LDL cholesterol, remnant cholesterol has not traditionally been a therapeutic target, despite growing evidence of its role in the pathophysiology of atherosclerosis. These particles exhibit high atherogenic and pro-inflammatory potential, and their metabolism is altered in states of insulin resistance and hepatic dysfunction, both common in diabetes. Epidemiological studies have shown its association with ischemic heart disease, peripheral artery disease, progression of nephropathy, and cardiovascular events in type 2 diabetes. In individuals with type 1 diabetes (T1D), the evidence is more recent but relevant: elevated levels of remnant cholesterol have been linked to persistent hyperglycemia, diabetic nephropathy, diabetic foot, subclinical myocardial dysfunction, and carotid atherosclerosis, even when LDL-C levels are within target range. Moreover, lifestyle factors such as physical activity and a healthy diet are associated with lower levels of remnant cholesterol, suggesting opportunities for non-pharmacological interventions. Despite this, treatments targeting remnant cholesterol have shown limited efficacy in reducing clinical events, and individuals with T1D remain underrepresented in clinical trials. Overall, this review highlights the need to incorporate remnant cholesterol into the assessment of residual cardiovascular risk and into personalized therapeutic strategies, especially for vulnerable populations such as those with T1D.

Endocrines doi: 10.3390/endocrines6030045

Authors: Maria Petersson Charlotte Höybye

Background: Pituicytomas are rare, low-grade gliomas arising from pituicytes in the posterior pituitary or infundibulum. Due to its rarity and nonspecific clinical and radiological characteristics, it is frequently misdiagnosed as pituitary adenomas or other sellar tumors. Aims: To present an overview of pituicytoma, including clinical presentation, radiological and histopathological characteristics, differential diagnosis and treatment strategies, illustrated by a case report. Methods: A literature review was conducted to contextualize our patient with a sellar tumor, and to highlight key diagnostic and therapeutic considerations. Results/Case report: A 12-year-old boy presented with visual disturbances. MRI revealed a well-defined contrast-enhancing sellar mass, and the patient underwent transsphenoidal surgery. The diagnosis was assumed to be a nonfunctioning pituitary adenoma (NFPA). Two years later a residual tumor was treated with proton irradiation. Six years after the radiotherapy, the patient had epistaxis. Imaging showed a tumor in the sphenoidale sinus, which was surgically resected. The tumor had histopathological features of pituicytoma and immunoreactivity for TTF-1 and S100. The tissue from the first operation was reviewed, showing more characteristics with pituicytoma than NFPA, leading to re-definition of the initial diagnosis. Follow-up has been without any signs of residual tumor. Conclusion: Our case and literature review emphasize the importance of considering pituicytoma in the differential diagnosis among sellar lesions. The diagnosis relies on a combination of preoperative imaging, intraoperative findings and histopathology. Pituitary surgery is the first-line treatment, and the outcome is generally good. Increased awareness of pituicytomas is necessary to improve preoperative diagnostic accuracy and guide appropriate management.

Endocrines doi: 10.3390/endocrines6030044

Authors: Nir Y. Krakauer Jesse C. Krakauer

Background/Objectives: Anthropometric indices based on height (H), weight (W), waist circumference (WC) and hip circumference (HC) can identify incident and future health risks. While BMI provides a standard for relative W (adjusted for H), there is no standard for indices using WC and HC. A body shape index (ABSI) and hip index (HI) have been proposed to extend to respectively WC and HC the same allometric power-law approach used to derive BMI to be independent of H. Here, we compared the mutually independent allometric set H, BMI, ABSI, HI with other proposed indices. Methods: We examined the formulas and rationales of published indices, and used Third National Health and Nutrition Examination Survey (NHANES III) cohort data to investigate their inter-correlations and association with mortality. Results: Many of the proposed indices are based on geometric (isometric) similarity, which does not match human body variability patterns. Unlike ABSI and HI, most proposed indices showed large correlations with BMI, complicating interpretation when considered together with BMI. Indices’ association with mortality risk were generally consistent with their correlations with BMI and ABSI. Combining the separable mortality risks associated with BMI and ABSI, even in a simplified way, outperformed any single index. Conclusions: With calls for incorporating additional indices incorporating WC and HC to supplement BMI in defining obesity, only ABSI and HI are independent of BMI. Additionally, separate risk estimates from these allometric indices can be readily combined to optimize overall risk assessment.

Endocrines doi: 10.3390/endocrines6030043

Authors: Mario Ruggiero Antonella Vicidomini Domenico Tafuri Filomena Mazzeo Rosaria Meccariello

Background: Obesity is a multisystemic health problem causing chronic diseases like diabetes or cardiovascular diseases, but also reproductive dysfunctions like infertility in adults or altered puberty onset in children. Exercise is a recognized intervention to control or prevent energy imbalance, thus deeply contributing to metabolic health in physiological and pathological conditions. The kisspeptin system (KS), the main gatekeeper of reproduction and puberty onset in mammals, is also an upcoming “metabolic sensor”, linking energy homeostasis to reproductive ability both centrally and peripherally. Objectives: This narrative review aims at summarizing recent evidence from animal models and human studies on the role of the KS in energy homeostasis, with a focus on the upcoming role of the KS as a metabolic sensor able to modulate the functionality of the hypothalamus–pituitary–gonad axis in males as an adaptive response to exercise. Methods: PubMed and Scopus search (date: 2015–2025; keywords: kisspeptin and metabolism, male reproduction or exercise; kisspeptin and doping). Results and Conclusions: This review article illustrates the crucial role of the KS in linking energy homeostasis and male reproduction at the central and peripheral levels, and modulation of the KS by exercise in physiological and pathological conditions. Due to the large amount of data from animal models, knowledge gaps occur in the analysis of the relationship among KS, energy homeostasis, male reproduction and exercise in humans, particularly in the case of overtraining. Lastly, kisspeptin inclusion in the doping list is also discussed.

Endocrines doi: 10.3390/endocrines6030042

Authors: Milen Hristov

Leptin, an adipocyte-derived hormone, plays a central role in the regulation of energy homeostasis by acting on distinct hypothalamic nuclei. This review explores recent advances in our understanding of leptin’s region-specific actions within the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and lateral hypothalamus, highlighting their contributions to appetite regulation, energy expenditure, and neuroendocrine function. In the hypothalamic arcuate nucleus, leptin’s differential regulation of pro-opiomelanocortin and agouti-related peptide/neuropeptide Y neurons is now complemented by the identification of novel leptin-responsive neuronal populations—such as those expressing prepronociceptin, basonuclin 2, and Pirt—as well as a growing array of cellular and molecular modulators, including secreted factors like angiopoietin-like growth factor, zinc-α2-glycoprotein, and spexin, intracellular regulators such as Rap1, growth factor receptor-bound protein 10, and spliced X-box binding protein 1. In the ventromedial hypothalamus, leptin integrates with both peripheral (e.g., cholecystokinin) and central (e.g., pituitary adenylate cyclase-activating polypeptide) signals, while epigenetic mechanisms, such as those mediated by Jumonji domain-containing protein D3, regulate leptin receptor expression and sensitivity. The dorsomedial hypothalamus is increasingly recognized for coordinating leptin’s effects on metabolism, circadian rhythms, and respiration through distinct neuronal populations, including a subset of neurons co-expressing GLP-1 receptors that mediate leptin’s metabolic effects. In the lateral hypothalamus, leptin modulates reward-driven feeding via GABAergic neuronal populations—circuits that are particularly susceptible to disruption following early life trauma. Together, these insights reveal a sophisticated neurobiological framework through which leptin orchestrates systemic physiology. Understanding the heterogeneity of leptin signaling opens new avenues for restoring leptin sensitivity and developing personalized therapeutic strategies to combat obesity and related metabolic disorders.

Endocrines doi: 10.3390/endocrines6030041

Authors: Acelya Yilmazer Dimitra Maria Zevla Karsten Kretschmer

Regulatory T (Treg) cells were first identified through the observation that Foxp3 gene mutations in mice and humans can result in their dysfunction, leading to a catastrophic multi-organ autoimmune syndrome. Since then, it has become increasingly evident that Foxp3+ Treg cells serve functions extending well beyond dominant tolerance and the mere prevention of autoimmune pathology. Highlighting their pivotal role in metabolic regulation, dysfunction of Treg cells has been implicated in the pathogenesis of both type 1 and type 2 diabetes. Emerging evidence further suggests that Treg cells contribute to tissue homeostasis and regeneration by facilitating repair processes, modulating immune responses to curb excessive inflammation, and supporting stem cell function in key metabolic organs such as muscle, adipose tissue, and the liver. This review aims to highlight recent progress in elucidating the functional specialization of Treg cells in the regulation of metabolic homeostasis. It explores the distinct roles of thymic and peripheral Treg cells in constraining pancreatic β-cell autoimmunity and the inflammation of metabolic organs, while also underscoring the pathogenic potential of Treg cell instability and their dedifferentiation into pathogenic effector cells. Investigating the roles of thymic and peripheral Treg cells in both forms of diabetes is a valuable endeavor, offering insight into their distinct and shared contributions to disease progression, while shedding light on immune dysregulation, metabolic inflammation, and immune–metabolic crosstalk. These insights may provide a foundation for the development of targeted therapeutic approaches directed at specific Treg cell subsets, offering the potential to attenuate disease progression or even entirely prevent its onset.

Endocrines doi: 10.3390/endocrines6030040

Authors: Elham Hosseini-Marnani Jessica A. Marathe James D. Triplett Md Kamruzzaman Kevin Yin Karen L. Jones Michael Horowitz Chinmay S. Marathe

Autonomic dysfunction of the stomach typically manifests as delayed gastric emptying or gastroparesis and is seen in individuals with both type 1 and 2 diabetes. However, impaired gastric motility is only modestly associated with the presence of upper gastrointestinal symptoms, and the diagnosis of gastroparesis essentially requires a formal measurement of gastric emptying, ideally employing a sensitive and precise technique such as scintigraphy. There is a bidirectional relationship between gastric emptying and glycemia: insulin-induced hypoglycemia accelerates, while acute elevations in blood glucose may delay gastric emptying. On the other hand, relatively more rapid emptying is associated with a higher initial rise in postprandial glucose. The management of gastroparesis requires an individualized approach, integrating dietary modifications, nutritional supplementation, pharmacological therapies, and, in severe cases, advanced interventions including gastrojejunostomy and gastric electrical stimulation. This review provides an overview of the pathophysiology and diagnosis of autonomic neuropathy of the diabetic stomach and discusses current clinical management strategies.

Endocrines doi: 10.3390/endocrines6030039

Authors: Sebastián Eustaquio Martín Pérez Isidro Miguel Martín Pérez Ruth Molina Suárez Jesús María Vega González Alfonso Miguel García Hernández

Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic accuracy of standard bone age (BA) methods remains uncertain in this context. Objective: To compare the diagnostic accuracy of the Greulich–Pyle atlas (GPA) and Tanner–Whitehouse 3 (TW3) methods in estimating skeletal age in girls with CPP and to assess the predictive value of serum hormone levels for estimating chronological age (CA). Methods: An observational, cross-sectional diagnostic study was conducted, involving n = 109 girls aged 6–12 years with confirmed CPP (Ethics Committee approval: CHUC_2023_86; 13 July 2023). Left posteroanterior hand–wrist (PA–HW) radiographs were assessed using the GPA and TW3 methods. Anthropometric measurements were recorded, and serum concentrations of estradiol, LH, FSH, DHEA-S, cortisol, TSH, and free T4 were obtained. Comparisons between CA and BA estimates were conducted using repeated-measures ANOVA, and ANCOVA was applied to examine the hormonal predictors of CA. Results: Both GPA and TW3 overestimated CA between 7 and 12 years, with the GPA showing larger deviations (up to 4.8 months). The TW3 method provided more accurate estimations, particularly at advanced pubertal stages. Estradiol (η2p = 0.188–0.197), LH (η2p = 0.061–0.068), and FSH (η2p = 0.008–0.023) emerged as the strongest endocrine predictors of CA, significantly enhancing the explanatory power of both radiological methods. Conclusions: The TW3 method demonstrated superior diagnostic accuracy over GPA in girls with CPP, especially between 7 and 12 years. Integrating estradiol, LH, and FSH into BA assessment significantly improved the accuracy, supporting a more individualized and physiologically grounded diagnostic approach.

Endocrines doi: 10.3390/endocrines6030038

Authors: Ethan A. Mills Beckey P. DeLucia Colton D. Wayne Taylor H. Jacobs Gail E. Besner Siddharth Narayanan

Pancreatic neuroendocrine neoplasms (PNENs) are a diverse group of rare tumor subtypes, representing less than 2% of all pancreatic tumors. Often detected late in the clinical course, they are associated with high rates of morbidity and mortality. Hereditary syndromes such as multiple endocrine neoplasia type-1 and von Hippel–Lindau are associated with the development of PNENs, although only a small portion of total tumors have a genetic basis. This review aims to explore the recent advances in laboratory diagnostics, imaging modalities, medical management, and surgical approaches to hormone-producing PNENs (including some common, less common, and some rare subtypes), with the goal of assisting physicians in the integration of evidence-based information into their practice.

Endocrines doi: 10.3390/endocrines6030037

Authors: Christian Battipaglia Anna Szeliga Veronica Setti Gregory Bala Peter Chedraui Alessandro D. Genazzani Blazej Meczekalski

Hormonal contraceptives (HCs) are widely used and generally well tolerated; however, their neuroendocrinological effects remain underappreciated in clinical decision-making. Beyond ovulation suppression, HCs influence brain function by modulating key neurotransmitters such as GABA, serotonin, and dopamine, as well as neurosteroids like allopregnanolone and β-endorphin. These interactions help explain why some users experience mood swings, anxiety, or changes in sexual desire, while others report improvements in well-being. In this narrative review, we explore how different estrogenic and progestin components affect central pathways involved in emotional regulation and cognition. Evidence suggests that estradiol or estetrol-based formulations combined with anti-androgenic progestins like drospirenone or nomegestrol acetate may offer a more favourable neuroendocrine profile, particularly in women with a history of mood disorders or hormonal sensitivity. Understanding these neuroendocrine mechanisms may support more personalized contraceptive choices, particularly in women with mood disorders and hormonal vulnerability.

Endocrines doi: 10.3390/endocrines6030036

Authors: Zhenqi Liu Linda A. Jahn Eugene J. Barrett

In healthy humans, insulin at physiological concentrations exerts acute vasodilatory actions on both resistance and terminal arterioles, leading, respectively, to increased total blood flow and the microvascular network volume being perfused. The process of increasing capillary network volume is frequently referred to as “capillary recruitment”. Together these two vascular actions of insulin enhance the delivery of oxygen, nutrients, and insulin itself to tissues. Both processes are diminished by insulin resistance. Here we examined interactions between insulin’s acute (within 2 h) actions on blood pressure (both central and peripheral) and on capillary recruitment in healthy controls and in four distinct groups of people with heightened cardio-metabolic disease (CMD) risk: individuals with obesity, metabolic syndrome, and type 1 or type 2 diabetes. Insulin increased microvascular blood volume (MBV) more effectively in controls than in each of the four CMD risk groups (p < 0.001). Conversely, insulin lowered both central and peripheral systolic pressure (p < 0.05 or less) in each of the CMD risk groups but not in the controls. The insulin-induced blood pressure decrements were greater in the metabolic syndrome, type 2 diabetes, and obesity groups (p < 0.05 or less) than in the controls. The greater blood pressure declines likely reflect decreased sympathetic baroreceptor reflex tone. These effects on blood pressure combined with the diminished dilation of terminal arterioles due to microvascular insulin resistance in the CMD risk subjects led to decreased distal microvascular perfusion as evidenced by changes in MBV. These findings highlight the complex interplay between insulin’s actions on resistance and terminal arterioles in individuals with a high CMD risk, underscoring the importance of addressing microvascular dysfunction in these conditions.

Endocrines doi: 10.3390/endocrines6030035

Authors: Luiza Santos de Argollo Haber Lucas Fornari Laurindo Rafael Fagundes de Melo Dennis Penna Carneiro Piero Biteli Henrique Villa Chagas Luciano Junqueira Mellem Jesselina Francisco dos Santos Haber Lance Alan Sloan Kátia Portero Sloan Sandra Maria Barbalho Eduardo Federighi Baisi Chagas

Background/Objectives: This study investigated the relationship between glycemic control and increased glomerular filtration rate (eGFR), as assessed by serum creatinine and the CKiD equation in children and adolescents with T1DM. Methods: This cross-sectional observational study involved 80 T1DM patients (4–19 years) attending the Interdisciplinary Center for Diabetes. Biochemical, anthropometric, and skeletal muscle mass parameters were evaluated. The GFR was estimated using the CKiD equation expressed in mL/min/1.73 m2. Results: Our results showed that nearly 19.0% of the included patients presented increased values for eGFR, and most had poor glycemic control. Patients with HbA1c levels above 8% presented eGRF > 130. There was a positive correlation between hyperglycemia, elevated HbA1c, and fat percentage with higher eGRF values. In addition, the reduction in lean mass and skeletal muscle mass was related to elevated eGRF. Conclusions: Our study indicates that children and adolescents with T1DM who have elevated HbA1c, lower lean mass, and less than five years of diagnosis of diabetes are more likely to present higher eGRF values.

Endocrines doi: 10.3390/endocrines6030034

Authors: Gonzalo Diaz Soto Pablo Fernández Velasco Pilar Bahillo Curieses

Background/Objectives: Continuous glucose monitoring (CGM) has transformed diabetes management, with time in range (TIR) emerging as a key glycemic metric. However, TIR lacks sensitivity to glycemic variability, leading to the introduction of time in tight range (TiTR), which defines a narrower range (70–140 mg/dL). This review synthesizes current evidence on TiTR’s clinical relevance and its potential to predict complications. Methods: A literature search was conducted, primarily using PubMed as the main database, to identify studies that specifically evaluate TiTR and its clinical implications, published until February 2025. Results: Preliminary data indicate that a 10% increase in TiTR is associated with a 23.8% reduction in microvascular complications. While TiTR aligns more closely with physiological glucose control, standardized targets remain undefined. Conclusions: This study provides clinicians with insights into optimizing glycemic control beyond traditional metrics. The correlation of TiTR with other glycemic markers and its association with diabetes-related complications suggest that TiTR can complement traditional measures to provide a more comprehensive assessment of glycemic status. From a clinical perspective, incorporating TiTR into routine practice may help personalize treatment strategies, improve risk stratification, and support more precise therapeutic decisions, particularly in patients using continuous glucose monitoring (CGM). Future research should refine TiTR thresholds and evaluate its integration into diabetes management, particularly in populations using advanced technologies.

Endocrines doi: 10.3390/endocrines6030033

Authors: Giorgio Sodero Luigi Antonio Moscogiuri Anna Camporeale Aniello Meoli Fabio Comes Paola Passoforte Giacomo Perrone Antonietta Villirillo Marilea Lezzi

Objective: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and clinical, hormonal, and auxological features in girls with idiopathic central precocious puberty (CPP). Methods: This retrospective study included 122 girls diagnosed with idiopathic CPP. Participants were stratified into three groups based on serum 25(OH)D concentrations: deficient (<20 ng/mL), insufficient (20–30 ng/mL), and sufficient (>30 ng/mL). Clinical and hormonal parameters were compared across groups. Spearman’s correlation and multiple linear regression analyses were used to explore the relationship between vitamin D levels and peak luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) stimulation. Results: No significant differences were observed among the vitamin D groups in terms of age at diagnosis, body mass index (BMI), or other auxological measures. However, serum 25(OH)D levels showed a weak but significant positive correlation with LH peak values (rho = 0.23, p = 0.037). In multivariable regression analysis, vitamin D levels remained an independent predictor of LH peak (β = 0.125, p = 0.036), whereas BMI standard deviations (SDS), growth velocity SDS, and age at diagnosis did not show significant associations. Conclusions: Higher serum vitamin D levels are independently associated with greater LH peak responses in girls with idiopathic CPP. These findings support a potential modulatory role of vitamin D in the neuroendocrine mechanisms underlying pubertal onset and warrant further prospective studies to clarify its clinical relevance.

Endocrines doi: 10.3390/endocrines6030032

Authors: James L. Li

Background/Objectives: Endocrine hormones play critical roles in regulating physiological processes, and previous studies have reported their associations with psychiatric disorders. Levels of endocrine hormones and the risk of developing psychiatric disorders are influenced by both genetic and non-genetic factors. However, the shared genetic basis underlying these associations remains largely unexplored. This study aims to dually evaluate the genetic correlations among endocrine hormones, including thyroid and sex hormones, as well as between endocrine hormone metrics and psychiatric disorders to identify potential shared genetic architectures. Methods: We obtained genome-wide association study summary statistics for six thyroid hormone metrics, three sex hormone metrics, and ten psychiatric disorders from predominantly European-ancestry populations. Genetic correlations were computed using linkage disequilibrium score regression after harmonizing variant data to ensure consistency across studies. Results: Significant genetic correlations were observed among thyroid and sex hormone metrics, indicating a strong shared genetic basis. Sex hormones exhibited multiple genetic correlations with psychiatric disorders, including negative correlations between sex hormone-binding globulin and attention-deficit hyperactivity disorder (ADHD) (p = 3.95 × 10−12) and major depressive disorder (p = 4.67 × 10−5), and positive genetic correlations with anorexia nervosa (p = 2.86 × 10−12) and schizophrenia (p = 2.00 × 10−4). Testosterone and estradiol had negative genetic correlations with ADHD and major depressive disorder, while testosterone had positive genetic correlations with anorexia nervosa and schizophrenia. Although thyroid hormone metrics did not exhibit Bonferroni-significant genetic correlations, nominal associations were observed, such as a negative genetic correlation between thyroid-stimulating hormone and major depressive disorder (p = 2.33 × 10−2). Conclusions: These findings suggest a shared genetic basis between endocrine hormones and psychiatric disorders, particularly for sex hormones. Future studies leveraging larger, more diverse populations are warranted to validate and extend the genetic correlations observed in this study.

Endocrines doi: 10.3390/endocrines6030031

Authors: Yuka Tanaka Bunpei Ishizuka Kazuhiro Kawamura

Background/Objectives: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder caused by mutations in the AIRE gene. Approximately 60% of affected females develop premature ovarian insufficiency (POI) by age 30, often most commonly due to steroidogenic autoantibodies. Although APECED is typically diagnosed in childhood, its reproductive implications are underrecognized. This study reports a case of successful fertility preservation in an adult woman with APECED and reviews the relevant literature. Methods: We describe the clinical course of a 37-year-old woman with genetically confirmed APECED who underwent ovarian stimulation for fertility preservation. A comprehensive PubMed search was also conducted to identify English-language case reports on fertility preservation in APECED-associated POI. Results: The patient experienced menarche at age 13, adrenal insufficiency at 14, and menstrual irregularities from age 18. Genetic analysis confirmed an AIRE mutation (NM_000383: exon 11: c.1400+1G>A). Given her relatively high anti-Müllerian hormone level, she opted for fertility preservation and underwent six cycles of ovarian stimulation, resulting in the cryopreservation of 17 mature oocytes. During ovarian stimulation, multiple follicular developments were observed, but serum E2 levels remained low. The literature review identified fewer than 20 reported cases addressing fertility preservation in APECED, highlighting its rarity and the lack of standardized management. Conclusions: Although APECED frequently leads to early POI due to impaired steroidogenesis, residual ovarian function may persist. Early assessment of ovarian reserve and timely fertility counseling are crucial, even in asymptomatic patients or those diagnosed in childhood. Reproductive planning should be integrated into the long-term care of women with APECED.

Endocrines doi: 10.3390/endocrines6030030

Authors: Giona Castagna Lucrezia Zanchi Alessandro Rossini Sara Cassibba Roberto Trevisan Silvia Ippolito

Cholestyramine, a bile acid sequestrant, has been used primarily for lipid-lowering purposes but has also shown potential in managing hyperthyroidism and thyrotoxicosis. The objective of this review is to assess the efficacy, safety, and clinical indications of cholestyramine in the treatment of hyperthyroidism, thyrotoxicosis, and associated conditions, particularly when conventional therapies fail or are contraindicated. A literature review of clinical guidelines, original research articles, and case reports was conducted, focusing on studies that explored cholestyramine’s use in the treatment of hyperthyroidism, thyrotoxicosis, and levothyroxine overdose. Cholestyramine has demonstrated effectiveness in rapidly reducing thyroid hormone levels in these conditions. Studies indicates that cholestyramine accelerates the reduction of T3 and T4 levels when used as adjunctive therapy alongside standard treatments, particularly in severe or refractory cases. Evidence from case reports also supports its utility in managing conditions such as amiodarone-induced thyrotoxicosis, thyroid storm, and preparation for thyroidectomy. However, the long-term effectiveness of cholestyramine remains uncertain, with potential challenges regarding gastrointestinal side effects and medication interactions. Further studies are needed to integrate it more widely into clinical guidelines for the management of thyroid disorders.

Endocrines doi: 10.3390/endocrines6020029

Authors: Roberto Paparella Arianna Bei Lorenzo Brilli Vittorio Maglione Francesca Tarani Marcello Niceta Ida Pucarelli Luigi Tarani

Precocious puberty, defined as the onset of secondary sexual characteristics before age 8 in girls, presents a diagnostic challenge in distinguishing between normal variants and pathological conditions requiring intervention. Central precocious puberty (CPP) results from early activation of the hypothalamic–pituitary–gonadal axis, whereas peripheral precocious puberty (PPP) arises from excess sex steroid production independent of gonadotropins. Benign variants, including premature thelarche and premature adrenarche, require careful differentiation to prevent unnecessary treatment. This review explores the physiological mechanisms governing puberty, the epidemiological trends influencing its early onset, and the genetic and environmental factors contributing to its variability in female children. A structured diagnostic approach incorporating clinical evaluation, hormone assessments, imaging studies, and genetic insights is discussed. Management strategies vary depending on the etiology, with gonadotropin-releasing hormone analogs recommended for CPP and targeted therapies for PPP. In contrast, benign variants often necessitate observation and periodic follow-up. Given the increasing prevalence of early puberty, further research is essential to refine diagnostic thresholds and optimize treatment protocols. Early and accurate identification of precocious puberty ensures appropriate intervention, mitigating potential risks associated with early maturation, including compromised adult height and psychosocial challenges.

Endocrines doi: 10.3390/endocrines6020028

Authors: Anastasios Serbis Chrysoula Kosmeri Natalia Atzemoglou Katerina-Marina Lampropoulou Lida-Eleni Giaprou Dimitrios Rallis Vasileios Giapros

Mini-puberty refers to the transient activation of the hypothalamic–pituitary–gonadal (HPG) axis during early infancy, lasting up to six months in boys and 12–24 months in girls. This phase represents the second activation of the HPG axis, following its initial activation during the second half of fetal life. At birth, the removal of the suppressive effect of placental estrogens on the HPG axis prompts a rise in both gonadotropins and sex steroid hormones, resulting in distinct clinical and laboratory markers of mini-puberty. While the clinical significance of mini-puberty remains partially understood, emerging evidence underscores its essential role in several aspects of human growth and development. In boys, testosterone influences penile growth, increases Sertoli cell numbers in the testes, and lays the foundation for future spermatogenesis. In girls, the increase in estradiol levels promotes follicular maturation and stimulates breast and uterine growth. Beyond the gonadal effects, mini-puberty appears to impact body composition, affecting body weight and promoting accelerated growth. Additionally, it may affect early psychosomatic and neural maturation, playing a role in several key aspects of the infantile brain. This narrative review examines recent findings on the physiology of the activation of the HPG axis before and after birth along with its significance in various aspects of human growth and development. In addition, mini-puberty-unique features in specific groups, such as preterm and small-for-gestational-age infants, are presented.

Endocrines doi: 10.3390/endocrines6020027

Authors: Rachelle Choi Jatin Vemuri Alekya Poloju Rishi Raj Anurag Mehta Amon Asgharpour Mohammad S. Siddiqui Priyanka Majety

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), previously referred to as Non-Alcoholic Fatty Liver Disease (NAFLD), is a prevalent chronic liver condition strongly linked to Type 2 Diabetes Mellitus (T2DM) and obesity. Globally, MASLD is the most common cause of chronic liver disease. The bidirectional relationship between MASLD and T2DM underscores the pivotal role of insulin resistance in disease progression, which contributes to hepatic steatosis, oxidative stress, and inflammation, forming a vicious cycle. MASLD is also associated with heightened risks of cardiovascular and chronic kidney diseases, necessitating comprehensive treatment approaches. While lifestyle interventions and weight loss remain the cornerstone of management, their sustainability is challenging. This review highlights the evolving pharmacological landscape targeting MASLD and its advanced form, Metabolic Dysfunction-Associated Steatohepatitis (MASH). Currently, Resmetirom is the only FDA-approved drug for MASH. Current and investigational therapies, including insulin-sensitizing agents like peroxisome proliferator-activated receptor (PPAR) agonists, glucose-lowering drugs such as sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA), drugs that target intermediary metabolism such as Vitamin E, de novo lipogenesis inhibitors, and emerging agents targeting the gut-liver axis and oxidative stress, are explored. These therapies demonstrate promising effects on hepatic steatosis, inflammation, and fibrosis, providing new avenues to address the multifaceted pathophysiology of MASLD.

Endocrines doi: 10.3390/endocrines6020026

Authors: Jennifer Nhieu Fatimah Najjar Li-Na Wei

Retinoic acid (RA) exerts biological effects through RA receptors (RARs) to regulate transcription. RA also elicits rapid, RAR-independent (noncanonical) activities mediated by Cellular RA Binding Protein 1 (CRABP1) to modulate cytosolic signaling. CRABP1 functions by forming protein complexes, named CRABP1 signalosomes, to modulate signal propagation in a cell type-specific manner. This review summarizes multiple CRABP1 signalosomes and their physiological functions. CRABP1 knockout (CKO) mice develop multiple phenotypes progressively throughout the lifespan. These include altered brain function, obesity, and insulin resistance starting at young adult stages, increased vulnerability to heart failure and altered serum exosome profiles in midlife, and motor deterioration and thyroid dysfunction (hypothyroidism) in later life. The mouse Crabp1 gene is tightly regulated by multiple epigenetic mechanisms, whereas human CRABP1 gene dysregulation is associated with multiple human diseases in which age is an important factor. Further, CRABP1 expression in human and mouse thyroid glands gradually increases with aging. This underscores the clinical relevance of CRABP1 signalosomes in maintaining health and the functions of certain cells/organ systems, especially in the thyroid and during the aging process. The CRABP1 sequence is highly conserved, likely due to its functional constraint in forming various signalosomes; its tight regulation ensures proper expression of CRABP1 required for the forming of various signalosomes critical to the health and functions of multiple cell types/organ systems. Finally, CRABP1-specific (without activating RARs) signaling pathway-selective compounds have been designed. It may be an attractive therapeutic strategy to exploit these CRABP1-specific compounds to modulate selective signaling pathways in certain disease conditions, such as thyroid dysfunction, to maximize efficacy while minimizing retinoid toxicity.

Endocrines doi: 10.3390/endocrines6020025

Authors: Cristian Petolicchio Giordano Spacco Eliana Delle Chiaie Maria Grazia Calevo Nicola Minuto Davide Carlo Maggi Diego Ferone Marta Bassi Francesco Cocchiara

Background/Objectives: The association between sexual dysfunction and diabetes is well known, but few studies have investigated its prevalence in type 1 diabetes (T1D). The aim of this study was to evaluate the prevalence of sexual dysfunction in a group of women with T1D, regardless of their age, and to compare its different prevalences in women treated with different insulin regimens. Methods: The population included 77 women affected by T1D, of which 16 were on Multiple Daily Injections (MDI) and 61 on Continuous Subcutaneous Insulin Infusion (45 on Advanced Hybrid Closed Loop System with catheter and 16 on patch pump). All participants completed the Female Sexual Function Index (FSFI), a questionnaire that evaluates several aspects of sexual function. Another questionnaire that evaluated general features, diabetes-specific features and sexual-specific features was proposed to every participant. Results: The overall prevalence of female sexual dysfunction was 49.3%. A correlation was demonstrated between the prevalence of female sexual dysfunction and age; another correlation was found between the prevalence of female sexual dysfunction and dyadic status. No correlation between glycemic control and sexual dysfunction was found. Conclusions: Women with T1D presented a high prevalence of sexual dysfunction, independently from glycometabolic disease control and insulin regimens; on the other hand, a significant correlation was demonstrated with age and dyadic status. Evaluation of sexual function in women with T1D appears to be important in clinical settings independently from disease control.

Endocrines doi: 10.3390/endocrines6020024

Authors: Inês Tomada

Lipedema is a chronic disease of the subcutaneous adipose tissue that mostly affects women. The etiopathogenesis of the disease is still poorly understood. Lipedema typically develops after major hormonal changes, such as puberty, pregnancy, and menopause. Alongside genetic susceptibility, the pathophysiological mechanism involving hormonal changes is mostly linked to aberrantly expressed estrogen receptors in adipose tissue. Lipedema has no known cure, and current therapies aim primarily to reduce symptoms, avoid complications, and slow the disease progression. Achieving or maintaining a healthy body composition, preserving or regaining mobility and functionality, preventing the progression of disease, and reducing pain and other symptoms are all possible outcomes of proper nutrition and weight management. Since nutrition may provide a long-term solution to control almost constant inflammation, it should be a major part of lipedema treatment. Despite the lack of a specific, scientifically supported diet for lipedema patients, several dietary approaches have been suggested. In this comprehensive narrative review, supported by published revisions and peer-reviewed studies following scrutiny of digital medical databases, the current state of knowledge and theories regarding the hormonal etiopathogenesis of lipedema are presented, as well as the role of nutritional intervention in reducing its symptoms and progression.

Endocrines doi: 10.3390/endocrines6020023

Authors: Sabrina Bossio Silvestro Antonio Ruffolo Danilo Lofaro Anna Perri Mauro Francesco La Russa

Background: Plastic pollution driven by human activities has become a critical global issue for human health. A growing literature demonstrates that micro- and nanoplastics (MNPs) contain endocrine-disrupting chemicals (EDCs) and other harmful compounds that enter the body easily, acting as agonists or antagonists for a wide range of hormonal receptors, and promoting endocrine toxicity. Endocrine disruption induced by MNPs occurs through the aberrant activation/inhibition of different signaling pathways that in addition to directly interfering with hormonal balances, trigger apoptosis, oxidative stress, and inflammation in endocrine cells. However, to date, the molecular mechanisms of these contaminants remain not completely elucidated. Furthermore, given the unanimous consensus on the negative impact of MNPs on human health, several methodologies have been developed to detect MNPs and contaminants not only in the environment but also in biological fluids and human tissues. Results: This review comprehensively summarizes the emerging experimental and clinical evidence explaining the mechanisms underlying the toxicity related to chronic plastic pollution in relation to the endocrine system. In addition, the review illustrates the new methodological approaches to detect MNPs in human biological samples, highlighting that employing complementary methods enables the precise characterization and quantification of MNPs. Conclusions: Future studies employing experimental, epidemiological, epigenetic, and multi-omics approaches are essential for understanding the short and long-term effects of MNPs on endocrine glands and developing effective strategies to mitigate their impact on human health.

Endocrines doi: 10.3390/endocrines6020022

Authors: Roberto Paparella Giulia Bellone Laura Rizza Norman Veccia Gabriele Ricci Mauro Calvani Salvatore Scommegna

Background: Oncocytic adenomas (OAs) of the thyroid, previously referred to as Hürthle cell adenomas, are uncommon tumors, particularly in pediatric populations, where they represent a minority of thyroid nodules. Due to their rarity and the potential difficulty in distinguishing benign from malignant forms on cytology, these adenomas present unique diagnostic and management challenges. Here, we report a pediatric case of a large OA of the thyroid, managed with surgical resection following inconclusive fine-needle aspiration (FNA) results. Case Presentation: A 13-year-old girl presented with an enlarging thyroid nodule. An ultrasound examination showed a large (26 × 16 mm), solid, isoechoic nodule with a hypoechoic halo. The FNA findings were inconclusive, indicating a follicular neoplasm with oncocytic features, classified as Bethesda IV. The patient underwent a hemithyroidectomy, and a histopathological examination confirmed an encapsulated OA without evidence of capsular or vascular invasion. The postoperative recovery was uneventful, and follow-up assessments showed no recurrence. Conclusions: OAs in pediatric patients are rare and may pose diagnostic challenges. This case highlights the importance of a comprehensive approach, including surgical resection, for definitive diagnoses in cases where FNA results are inconclusive. Further studies are warranted to establish guidelines for the management of oncocytic thyroid neoplasms in pediatric patients, as well as to understand their clinical behavior in this population.

Endocrines doi: 10.3390/endocrines6020021

Authors: Vittorio Ferrari Giacomo Biasucci Egidio Candela Rita Ortolano Federico Baronio Marcello Lanari

Background: Vitamin D is essential for neonatal health, with maternal vitamin D status crucial in fetal development and neonatal outcomes. During pregnancy, vitamin D is transferred to the fetus via the placenta, forming an initial reserve. Postnatally, neonates rely on maternal levels and supplementation due to limited sunlight exposure and immature skin synthesis. Objectives: This review evaluates neonatal vitamin D deficiency’s causes and clinical consequences, emphasizing its impact on newborn and infant health. Results: Maternal vitamin D levels strongly correlate with neonatal 25(OH)D concentrations, influencing birth weight, bone development, and overall health. Supplementation during pregnancy reduces the risk of severe deficiencies and rickets, particularly in exclusively breastfed infants who require daily supplementation of 400 IU. Formula-fed infants typically meet requirements through fortified formulas. Preterm infants are at a higher risk of complications like osteopenia and rickets, with mixed evidence on the effectiveness of higher supplementation doses. Vitamin D is critical in skeletal development, immune function, and protection against respiratory infections such as bronchiolitis and pneumonia. Deficiency is associated with respiratory distress syndrome (RDS), atopic dermatitis, and impaired bone mineralization due to reduced placental calcium transport. Conclusions: Vitamin D deficiency during pregnancy and infancy has significant clinical implications, including impaired skeletal and immune development. Maternal and neonatal supplementations are critical to prevent deficiencies, particularly in high-risk groups such as preterm and breastfed infants. Targeted strategies are essential to improve neonatal health outcomes and prevent complications.

Endocrines doi: 10.3390/endocrines6020020

Authors: Aikaterini Theodosiadi Ilektra Toulia Maria G. Grammatikopoulou Fotini Adamidou Danai Chourmouzi Charalampos Antachopoulos Athanasios E. Evangeliou Dimitrios G. Goulis Kyriaki Tsiroukidou

Background/Objectives: Hyperprolinemia is a rare autosomal recessive disorder with two distinct types: I (HPI) and II (HPII). The clinical presentation varies widely, with some individuals remaining asymptomatic and others exhibiting neurological, renal, or auditory defects and seizures. However, it has never been associated with hypoglycemia. The present case report describes a 5-year and 6/12-month-old boy with HPII, with an episode of severe hypoglycemia and Pituitary Stalk Interruption Syndrome (PSIS) with isolated growth hormone (GH) deficiency (GHD). Results: The boy was presented to the Department of Pediatric Endocrinology for routine thyroid function assessment due to hypothyroidism. He was diagnosed with HPII at the age of 2 years old during an investigation for seizure episodes. Clinically, the boy exhibited attention deficit hyperactivity disorder (ADHD) and a reduction in growth velocity (1.6 cm/year). Hematological and biochemical analyses were within the reference range. Hormone profiling revealed lower-than-expected insulin-like growth factor-1 (IGF-1) concentrations, prompting a GH stimulation test, which, in turn, revealed GHD. Brain magnetic resonance imaging (MRI) showed features consistent with PSIS. Noteworthy is the occurrence of severe hypoglycemia during an episode of gastroenteritis, leading to hospitalization, eventually attributed to GHD. Following the exogenous administration of recombinant human GH, the boy exhibited increased growth velocity, with no adverse events over the follow-up period. Conclusions: Hyperprolinemia is a rare condition; in this context, the occurrence of severe hypoglycemia accompanied by a low growth velocity poses a challenge for the clinical pediatrician. Furthermore, the coexistence of hyperprolinemia and PSIS has never been reported in the literature thus far.

Endocrines doi: 10.3390/endocrines6020019

Authors: Gordon L. Klein

This review examines the relationship between cholesterol and bone resorption. It seeks to elucidate the dependence of bone turnover on cholesterol metabolism by highlighting the common inhibitory effect of both statins and nitrogen-containing bisphosphonates on cholesterol biosynthesis and bone resorption as well as on bone density. Moreover, this paper also discusses the epidemiologic studies of the effects of nitrogen-containing bisphosphonates on all-cause and cardiovascular mortality using the latest publications to reinforce the relationship between bone resorption and cardiovascular disease. This review will also discuss the role of lipoproteins in supplying cholesterol to both osteoclasts and osteoblasts and the effects of doing so on both of these bone cells and their precursors. As inflammation is a major factor in both bone resorption and cardiovascular calcification, this article will also discuss the role of cholesterol in triggering inflammatory responses. Finally, this paper will raise questions unanswered to date that bear on the relationship between lipid metabolism, bone resorption, and cardiovascular disease.

Endocrines doi: 10.3390/endocrines6020018

Authors: Jan Tesarik

Background: This paper briefly reviews the most important endocrine features of primary ovarian insufficiency (POI) and shows their relevance for the diagnosis and treatment of this condition. Introduction: Endocrine disturbances in POI cause problems for both the fertility and general health status of the affected women. Both subfertility and infertility result from the depletion of growing ovarian follicles which, in its turn, is the causative factor of hypoestrogenism; this is responsible for most of the general health problems affecting women. Method: Search of literature. Results and conclusion: A combination of high-serum follicle-stimulating hormone (FSH) and low 17β-estradiol (E2) concentrations is a key feature characterizing POI and is the decisive element for POI diagnosis. However, an in-depth search for possible genetic and non-genetic causes is important for adequate counseling regarding prevention and early intervention. The treatment of general health problems, based on correcting hypoestrogenism through hormone replacement therapy (HRT), is relatively easy. On the other hand, resolving infertility is a much more difficult task, and oocyte donation is the only really efficient instrument. Fertility preservation is a suitable alternative in patients with early POI diagnosis, in whom some viable follicles are still present in the ovaries. In patients who refuse oocyte donation, intraovarian injection of autologous platelet-rich plasma and in vitro activation of dormant follicles may be considered. Other innovative treatments, such as stem cell therapies or nuclear transfer, are currently under investigation.

Endocrines doi: 10.3390/endocrines6020017

Authors: Evija Silina Maksims Zolovs Iveta Dzivite-Krisane Inta Zile Maris Taube

Background/Objectives: Chronic somatic diseases are significant risk factors for the development of mental disorders. Type 1 diabetes mellitus (T1D) is the most common chronic endocrine pathology in children. Treatment requires nutrition management, physical activity, lifelong insulin therapy, and proper self-monitoring of blood glucose. It is complicated and therefore may result in a variety of psychosocial problems for children, adolescents, and their families. Considering the rapidly growing incidence of type 1 diabetes in the pediatric population of Latvia, it is important to detect and prevent the risks of anxiety and depression in families with children suffering from type 1 diabetes. Methods: This was a quantitative interdisciplinary cross-sectional study to determine the prevalence of anxiety and depression in adolescents with T1D and their parents. Two tools were used to detect the presence of symptoms of anxiety and depression: the Generalized Anxiety Disorder Scale-7 (GAD-7) and the Patient Health Questionnaire 9 (PHQ-9) scale. Results: A total of 812 respondents were eligible for screening. Anxiety and depression symptoms were seen significantly more frequently in the study group than in the control group. The study found negative effects of anxiety and depression on the compensation of diabetes. Conclusions: Adolescents with type 1 diabetes and their parents are more predisposed to anxiety and depression symptoms than somatic healthy children and their parents, thus worsening disease control and prognosis.

Endocrines doi: 10.3390/endocrines6020016

Authors: Reiko Saito Yukihiro Hasegawa

Precocious puberty (PP) is characterized by the early onset of secondary sexual characteristics and accelerated growth, which often result in compromised adult height (AH). Central precocious puberty (CPP), a subset of PP, is treated with gonadotropin-releasing hormone analogs (GnRHa) to suppress premature hormonal activation and delay epiphyseal closure, thereby preserving height potential. The present review examined the effects of GnRHa on AH outcomes in girls with idiopathic CPP. Although AH is greater with GnRHa therapy than without it, the treatment does not consistently restore the patient’s genetic potential. The benefits of the treatment are most evident in girls in whom idiopathic CPP is diagnosed before 6 years of age and they achieve a height gain of 4.5–14.1 cm, which is unattainable without treatment. However, the treatment of older children (ages 6–8) shows conflicting results, with the AH outcome varying among previous reports. In particular, slowly progressive CPP is known to have a favorable height prognosis even without treatment. Another factor influencing the AH prognosis is the timing of GnRHa discontinuation; the best time to discontinue GnRHa therapy for the best AH outcome is reportedly the bone age of approximately 12 years. In conclusion, although GnRHa therapy significantly improves the AH, especially in early-onset CPP, its effectiveness is uncertain in borderline or late-onset cases. Further research is required to formulate more precise criteria for patient selection and treatment discontinuation to optimize height outcome in girls with idiopathic CPP.

Endocrines doi: 10.3390/endocrines6020015

Authors: Marina Valenzano Ruth Rossetto Giaccherino Loredana Pagano Sara Garberoglio Roberto Garberoglio

Background/Objectives: Understanding sex-based differences in both the pathophysiology and clinical presentation of diseases is necessary to improve health care towards precision medicine. The endocrine system is deeply involved in human health, and endocrine diseases may be influenced by steroidal hormone exposure. Thyroid nodular disease and differentiated thyroid cancer, in particular, show a high prevalence in the female sex; however, little is known about sex-related differences in risk factors and clinical presentation. This study aims to assess whether morphological differences, which can be detected by ultrasound examination, can be related to sex in order to refine diagnostic approaches and oncological risk classification. Methods: A retrospective observational study on 1355 ultrasound images of thyroid nodules obtained from 2017 to 2020 at a single university center was conducted. The images were reviewed by a single observer blinded to the patient’s sex and the cytological nature of the nodules. The qualitative description, size, anatomical location and oncological risk classification were assessed. Results: A taller-than-wide shape (anteroposterior/craniocaudal axis ratio > 1) was found to be more frequent in men than in women (6.7% vs. 3.6%, p = 0.027); the nodular volume was significantly larger in males (p << 0.01) than in females. Significant tropism for the upper lobe and isthmus was described in women (26% vs. 16.5%, p = 0.011) and for medium–lower thyroid lobes in men (83.5% vs. 73.8%, p = 0.011). Background thyroiditis was more common in women, while the number of cytological diagnoses of malignant or likely malignant nodules was higher than expected in men (9% vs. 6%, p = 0.01). Conclusions: Thyroid nodules show different distributions, in terms of a larger volume, more frequent taller-than-wide shape and lobular caudal location, in men vs. women. These results should be confirmed by further investigations, and the underlying mechanism should be clarified. However, our explorative research is of interest due to its novelty and possible future clinical implications.

Endocrines doi: 10.3390/endocrines6010014

Authors: Raul Cosme Ramos Prado Tamires Nunes Oliveira Bryan Saunders Roberta Foster Zsuzsanna Ilona Katalin de Jármy Di Bella Marcus W. Kilpatrick Ricardo Yukio Asano Anthony C. Hackney Monica Yuri Takito

Objectives: This study investigated the effects of the menstrual cycle phases on cortisol levels before and after a maximal incremental exercise test in women with and without premenstrual syndrome (PMS). Methods: Nineteen healthy, active and eumenorrheic women completed five maximal incremental exercise tests; three of those were performed at specific phases of the menstrual cycle (i.e., menses, follicular, and luteal). The participants were allocated into two groups according to the presence of PMS (n = 11) or absence of PMS (NO-PMS, n = 8). Samples of blood were collected before and after each experimental test. A three-way ANOVA was conducted to compare the differences between menstrual cycle phases (i.e., menses, follicular, and luteal), time (before and after) and groups (PMS and NO-PMS). Results: The results demonstrated an alteration of cortisol across the menstrual cycle, with cortisol levels significantly (p < 0.05) higher during the follicular phase (mean = 11.0 µg/dL, CI95% = 9.1, 12.9) compared to the luteal phase (mean = 8.6 µg/dL, CI95% = 7.2, 10.4) in the PMS and NO-PMS groups. There was no difference (p > 0.05) in cortisol levels for groups or time. Conclusions: This study observed significant cortisol fluctuations across the menstrual cycle phases in women with and without PMS. Future studies should consider alternative maximal incremental test protocols and incorporate a more comprehensive hormonal profile to provide a deeper physiological understanding of this population.

Endocrines doi: 10.3390/endocrines6010013

Authors: Ava M. Boyle Olivia J. Holland Deanne H. Hryciw

Introduction: Early-life neurological and inflammatory disorders significantly affect long-term cognitive, social, and emotional development. The ‘Developmental Origins of Health and Disease’ hypothesis states that an adverse intrauterine environment may predispose offspring to chronic health conditions due to altered growth and development. Factors measured in umbilical cord blood can provide information about the status of the in utero environment during development. Evidence indicates that umbilical cord blood adipokines, namely leptin and adiponectin, may influence fetal programming and could be useful in predicting offspring health outcomes. Leptin and adiponectin are crucial in energy homeostasis, immune response, and placental function, and some studies suggest that altered concentrations may increase the risk of developing inflammatory and neurological disorders in later life. Further, limited studies have demonstrated sex-specific differences in adipokine concentrations and disease risk. Conclusions: Understanding the role of umbilical cord blood adipokines in fetal programming could offer new insights into early risk prediction and intervention strategies, promoting better health outcomes for children at risk of neurological and inflammatory diseases due to an adverse maternal environment during pregnancy.

Endocrines doi: 10.3390/endocrines6010012

Authors: Haruko Yokosuka

Background/Objectives: Dienogest 0.5 mg tablets (DNG0.5) taken twice daily (1 mg/day) are more effective than cyclic low-dose estrogen/progestin/combined oral contraceptive (LEP/COC) in ameliorating dysmenorrhea pain and are recommended for dysmenorrhea treatment in Japan. However, their efficacy has not been directly compared with continuous LEP/COC regimens. Here, we evaluated the effectiveness of DNG0.5 compared to Yazflex® (YZF), a continuous LEP, in treating dysmenorrhea. Methods: The efficacy of DNG0.5 in treating dysmenorrhea was compared retrospectively with that of Yazflex, the longest continuously administered LEP/COC available in Japan. Results: The improvement rates of dysmenorrhea scores at 3 and 6 months post-treatment were 59.1% and 66.4% in the LEP group (n = 113) and 88.1% and 96.4% in the DNG0.5 group (n = 125), respectively. The complete resolution rate of dysmenorrhea at 6 months was 88.0% in the DNG0.5 group and 23.9% in the LEP group. These findings indicate that DNG0.5 was significantly more effective than LEP (p < 0.01). DNG0.5 exerted an early pain-suppressing effect, which continued to increase thereafter. Furthermore, the presence of endometrial polyps, uterine fibroids, or adenomyosis, which are risk factors for irregular genital bleeding, was examined. Among these, endometrial polyps were particularly more likely to cause bleeding and potentially reduce the effect of DNG0.5; however, even with these three risk factors, DNG0.5 was more effective than LEP in reducing pain. Conclusions: Dienogest was more effective than LEP in managing dysmenorrhea, even at a dosage of 0.5 mg twice daily. However, factors affecting irregular vaginal bleeding should be considered when prescribing DNG0.5.

Endocrines doi: 10.3390/endocrines6010011

Authors: Rodrigo J. De Marco

Stress responses enable vertebrates to adapt to environmental challenges while maintaining homeostasis. Zebrafish larvae are a valuable model for studying stress regulation due to their genetic accessibility and rapid development. This review examines the integration of zebrafish larvae with water vortex protocols to investigate hypothalamic–pituitary–interrenal (HPI) axis functionality during early development, advancing stress research while adhering to the 3Rs principle. Key publications are reviewed to discuss the potential of water vortices in zebrafish larvae for studying stress responses. These purely physical stressors exploit the innate positive rheotropism of developing zebrafish, offering precise control over timing and strength while avoiding confounding factors associated with chemical or biological interventions. The approach enables reproducible assessments of stress responses. The reviewed publications show advances in understanding cortisol response dynamics, glucocorticoid feedback, and early-life stress-induced changes in HPI axis function. Key findings include detailed cortisol patterns after acute stress, rapid glucocorticoid receptor-mediated feedback regulating cortisol levels, developmental shifts in HPI axis sensitivity, and reduced cortisol reactivity following early-life challenge (ELC). Vortex-driven ELC affects cortisol regulation, neuropeptide expression in the nucleus preopticus, and stress-related gene transcription. Combining zebrafish larvae and vortex protocols provides a robust and innovative platform for investigating stress biology. This approach leverages active, demanding behaviour to study stress mechanisms under controlled conditions, yielding insights with broad applications across vertebrate models while supporting the 3Rs principle. Future studies can build on these findings to address unresolved questions in stress regulation and enhance our understanding of adaptive physiological mechanisms.

Endocrines doi: 10.3390/endocrines6010010

Authors: Ligia J. Dominguez Nicola Veronese Lee Smith Francesco Saverio Ragusa Giovanna Di Bella Giuseppe Battaglia Antonino Bianco Mario Barbagallo

A balanced diet and regular physical activity are essential for maintaining musculoskeletal health. Key nutrients such as calcium, vitamin D, and protein are especially important for preventing falls and fractures. While the benefits of these nutrients are well-established, other dietary components have not been studied as extensively. For instance, vegetables, which are rich in nutrients vital for muscle and bone health, play a crucial role in preventing falls and fractures. Over recent decades, a great emphasis has been given to the combinations of nutrients and foods in dietary patterns that may have synergistic or antagonistic effects. Despite the challenges in researching the impact of nutrition and physical activity on musculoskeletal health due to the extensive heterogeneity of the results, healthcare professionals should continue to promote healthy eating and regular physical activity, and these principles should be emphasized in public health initiatives. Ultimately, a sufficient and balanced diet, abundant in plant-based foods and low in processed or discretionary foods, along with consistent physical activity, remains the most effective strategy for the prevention of musculoskeletal issues. This article aims to review the updated literature of recent years on the links between nutrition and physical activity with bone and skeletal muscle health.

Endocrines doi: 10.3390/endocrines6010009

Authors: Elizabeth K. Vu Grant Kim Mitchell J. Shimak Ismael Y. Karkache Jinsha Koroth Emily Chavez Samuel Mitchell Rachel B. Clark Kim C. Mansky Elizabeth W. Bradley

Background/Objectives: In contrast to endochondral bone healing, the process of intramembranous bone regeneration is poorly understood. This limits our ability to repair and regenerate the craniofacial skeleton to either correct deformity or optimally heal tissues following injury. While there are several preclinical models of intramembranous regeneration within the craniofacial skeleton, some are not load bearing and others are technically challenging. The goal of this pilot study is therefore to describe a simple method for induction of cortical defects within the mandible that does not involve compounding injury to the surrounding tissues. Methods: Single cortex defects were generated in the mandible body of 8-week-old male and female mice. The extent of bone regeneration within the defect was characterized at days 0, 3, 14, and 28 following defect generation via micro-computed tomography and histology. Conclusions: Observed healing was predictable and reproducible and resulted in intramembranous bone formation. This model will help aid the understanding of intramembranous bone healing in load bearing bones (e.g., mandible) within the craniofacial skeleton

Endocrines doi: 10.3390/endocrines6010008

Authors: Álvaro Fernández-Sánchez Diego Meneses Emma Raquel Alegre Bellasai Jersy Cárdenas-Salas Amalia Paniagua Clotilde Vázquez Jorge Gabriel Ruiz-Sánchez

Background/Objectives: Primary aldosteronism (PA) is associated with a higher cardiovascular disease (CVD) risk than essential hypertension (EH) and is mainly driven by the excess of aldosterone production. Studies suggest a relationship between aldosterone and parathormone (PTH) homeostasis. Excessive PTH levels seem to also be associated with CVD. The impact of PTH levels on CVD in PA patients has not been totally elucidated. We evaluated the associations of PTH levels and hyperparathyroidism with CVD in patients with PA and EH. Methods: A cross-sectional study of a group of 67 patients was carried out, with 35 patients with PA and a control group of 32 patients with EH. We looked at the presence of CVD and data on the factors associated with its presence were collected and analyzed. A binary logistic regression was performed to assess multivariate relationships. Results: PA patients had higher PTH levels compared to the EH group (64 ± 42 vs. 39 ± 13 pg/mL, p = 0.004). Significative differences in PTH levels were observed according to the grade of hypertension in PA patients. Both hyperparathyroidism and CVD were found at higher rates in patients with PA. Patients with CVD exhibited significantly higher PAC values than patients without it (41.4 ± 18 vs. 21.4 ± 12 ng/dL, p < 0.001). Patients with hyperparathyroidism had higher rates of CVD than patients without it (58 vs. 24%, p = 0.018). Patients with PA and hyperparathyroidism manifested a higher rate of CVD than patients without this combination. A logistic regression showed an independent association of PAC and hyperparathyroidism with the presence of CVD in the total cohort. Conclusions: Hyperparathyroidism is associated with a higher probability of CVD both in PA and EH. The presence of hyperparathyroidism in PA seems to exacerbate the risk of CVD, with higher PTH levels associated with higher grades of hypertension in this cohort.

Endocrines doi: 10.3390/endocrines6010007

Authors: Carl De Crée

Alex Vermeulen (1927–2023) was a leading Belgian endocrinologist whose name will forever remain linked to testosterone and androgen metabolism. As a dedicated scientist and clinician, he made seminal contributions to endocrinology throughout his career. These included the development of chromatography and radioimmunoassays of steroid hormones. His work also focused on the biological significance and metabolism of corticosteroids and androgens, and he defined key concepts in the role of steroid hormones in the human menstrual cycle, pregnancy, and menopause. His love for math, endocrinology, and problem-solving led to a formula for the estimation of free testosterone in serum, which has not been improved upon to date and is still in use worldwide. He contributed to enhancing our understanding of the role that male sex hormones may play in a variety of clinical problems in endocrinology, including bone health, type 2 diabetes, and, especially, endocrine function in aging males. Alex Vermeulen literally was “a giant in endocrinology”. Beyond his scientific contributions, Vermeulen was a wise and engaging mentor, a Renaissance man, and an aficionado of the finer things in life. He owned an eclectic choice of modern artworks, all of which he bequeathed to the Ghent Museum of Fine Arts, thus significantly enhancing the museum’s art patrimony.

Endocrines doi: 10.3390/endocrines6010006

Authors: Eleftheria Taousani Konstantinos-Georgios Papaioannou Gesthimani Mintziori Maria G. Grammatikopoulou Angeliki Antonakou Maria Tzitiridou-Chatzopoulou Stavroula Veneti Dimitrios G. Goulis

Gestational diabetes mellitus (GDM) is a prevalent condition impacting approximately 14% of pregnancies globally, posing significant health risks to mother and child. This review explores the role of diet, physical activity (PA), and sedentary behavior (SB) in preventing and managing GDM. Consumption of fish, fruits, vegetables, and legumes, and adherence to healthy dietary patterns, like the Mediterranean diet, are linked to lower GDM risk. Higher levels of PA and structured exercise consistently show protective effects against GDM, enhancing glucose metabolism and insulin sensitivity. Conversely, SB is a risk factor for GDM; prolonged sedentary periods detrimentally affect glucose regulation. The review emphasizes the need for a combined approach integrating healthy dietary habits, regular PA, and reduced SB to mitigate GDM risk effectively. Future research should prioritize standardized assessment methods and personalized lifestyle interventions to optimize GDM prevention strategies, ultimately informing public health guidelines and clinical recommendations for healthier pregnancies and better long-term outcomes.

Endocrines doi: 10.3390/endocrines6010005

Authors: Borros Arneth

The endocrine system relies on complex cell signaling and epigenetic processes to adjust to the body’s needs. However, stressors such as climate change and heat can disrupt the endocrine system. This study aims to collect and systematically review evidence from publications exploring how climate change impacts endocrine laboratory parameters. The review process included developing research questions, defining inclusion and exclusion criteria, conducting database searches, screening and selecting relevant publications, collecting and analyzing data, interpreting the findings, and drawing conclusions. This review identified multiple endocrine parameters linked to climate change and the mechanisms by which various stressors disrupt endocrine function. Climate change, especially heat stress, affects the production and levels of key hormones. The mechanisms underlying the disruption of key hormones are also explored in this paper. This review provides a clear overview of how climate change influences endocrine parameters and outlines the processes underlying stress-triggered endocrine disruption.

Endocrines doi: 10.3390/endocrines6010004

Authors: Erik Lindstrom Jessica Deis David A. Bernlohr Xiaoli Chen

Background: Lipocalin 2 (LCN2), also known as neutrophil gelatinase-associated lipocalin, is a 25 kDa protein involved in immune defense, inflammation, and metabolism. Results: LCN2 is widely expressed across various tissues, including immune cells, bone, adipose tissue, liver, kidneys, lung, spleen, and epithelial cells, and exhibits sex- and fat depot-specific expression patterns. Structurally, LCN2 contains a hydrophobic lipid-binding pocket and glycosylation sites, enabling it to interact with diverse ligands and form dimers. In innate immunity, LCN2 plays a critical role by sequestering iron-laden siderophores, thereby restricting bacterial growth. Beyond its role in infection control, LCN2 is implicated in metabolic inflammation and diseases such as obesity and diabetes. Recent research has highlighted a pivotal role for LCN2 in mitochondrial phospholipid metabolism and mitochondrial function. In metabolic diseases and mitochondrial metabolism, LCN2 appears to display paradoxical effects. While some studies link it to improved insulin sensitivity, glucose regulation, and mitochondrial function, others associate it with insulin resistance, obesity, and mitochondrial dysfunction. These inconsistencies may arise from differences in experimental conditions and study populations. Conclusions: This review provides an up-to-date summary of LCN2’s multifaceted roles in obesity, diabetes, energy balance, and mitochondrial function, emphasizing its context-dependent effects. LCN2 appears to have dual roles, exerting both protective and detrimental outcomes depending on the physiological or pathological context, sex, cell types, and experimental conditions. Further research is necessary to unravel its complex functions and resolve conflicting findings, particularly in metabolic disorders.

Endocrines doi: 10.3390/endocrines6010003

Authors: Omorogieva Ojo Gloria Aderonke Otunola Omotayo Rebecca Oshungade Beverly Joshua

Background: Type 2 Diabetes (T2D) is increasingly becoming a critical healthcare priority globally. Medical interventions are primary strategies for managing diabetes, but more recently, diet/nutrition therapy, including the use of functional food products such as cinnamon and/or cinnamon products, has garnered considerable attention. The focus of this systematic review and meta-analysis is to examine whether cinnamon improves blood glucose parameters, body mass index, and inflammatory markers in people with T2DM. Method: PRISMA and PICOS frameworks were used for the review. EBSCOhost was used to search for relevant literature in health science research databases, while EMBASE and reference lists were used to access other relevant articles. Results: For systematic review and meta-analysis, 14 and 12 studies, respectively, were included (five from Iran, two each from the USA and India, and one each from the UK, China, Germany, Portugal, and Iraq). All participants had T2DM with ages ranging from ≥30–65 years. The effect of cinnamon on glycaemic control and other parameters did not follow a regular pattern. Effect on HbA1c (nine studies and 605 participants; MD of −0.07 (95% CI, −0.13, −0.01, p = 0.02), postprandial blood glucose (PBG) and BMI showed significant (p < 0.05) reductions. However, cinnamon exhibited no significant (p > 0.05) impact on FBG (MD of −1.73 (95% CI, −3.98, 0.52, p = 0.13), CRP, TNF-α, and IL-6 in people with T2D; neither did the sensitivity test reveal any change in relation to these parameters. Conclusions: Cinnamon or cinnamon extracts/products are significantly effective in diabetes management through reduction in HbA1c, PBG, and BMI.

Endocrines doi: 10.3390/endocrines6010002

Authors: Lisa M. Raven Jacqueline R. Center Christopher A. Muir

Background: Osteoporosis is common in transplant recipients, and fracture risk is high. Standard treatment is with anti-resorptive medications. Despite high fracture rates, there are limited data on the use of anabolic bone therapies in transplant recipients. Aim: To evaluate skeletal outcomes after treatment with romosozumab for 12 months in heart and lung transplant recipients. Methods: Retrospective analysis of transplant recipients who completed 12 months of romosozumab treatment at a single centre. Results: Six transplant recipients completed 12 months of romosozumab treatment, commenced after a median of 3 years post transplant (range 2–20). Four patients (66%) were still receiving prednisolone treatment at the time of starting romosozumab. All patients had a history of fracture and had previously received anti-resorptive therapy (4 with zoledronate, 2 with denosumab for >2 years). Following completion of romosozumab treatment, all patients were consolidated with zoledronate or denosumab. Bone mineral density (BMD) was measured prior to and after completion of romosozumab treatment. The median baseline lumbar spine (LS) T-score was −2.3 SD (range −3.1 to +0.9) and total femur T-score was −2.2 SD (range −2.9 to −1.6). Most (5/6) patients experienced an increase in BMD at the LS (median change +7.1%). Most (5/6) patients did not experience clinically significant change in total femur BMD, apart from one patient who experienced a 9% gain. Three patients (50%) experienced subsequent fractures during (1/3) or after completing (2/3) romosozumab treatment. Conclusions: These cases demonstrate severe osteoporosis in transplant recipients. Most patients in our case series had improvement in LS BMD following romosozumab treatment, yet new fractures still occurred during follow-up. The appropriate use of romosozumab in heart and lung transplant patients with osteoporosis requires further study.

Endocrines doi: 10.3390/endocrines6010001

Authors: Daniel Venegas-Pino Brooke D’Mello Mark De Leon Geoff H. Werstuck

Objective: The effect of testosterone on the development of cardiovascular disease (CVD) is of interest due to the higher risk of CVD in men. This study aims to examine the impact of testosterone depletion and supplementation on atherosclerosis progression in normoglycemic and hyperglycemic mouse models. Methods: Male apolipoprotein E-deficient (ApoE−/−) and hyperglycemic (insulin deficient) ApoE−/−Ins2+/Akita mice were fed a standard chow diet and were either castrated or subjected to sham operations at 5 weeks of age. At 8 and 16 weeks of age, subsets of these mice were implanted subcutaneously with a silastic tube containing either 40 µL of dihydrotestosterone (DHT, 25 mg/mL) or sesame oil as a vehicle control. Survival was monitored and all remaining mice were sacrificed at 24 weeks of age. Blood, heart, and aortic samples were collected for analysis. Metabolic parameters were evaluated, and atherosclerotic lesion volumes were measured at the aortic sinus and in en face whole aorta mounts. Results: Castration significantly promoted atherosclerosis in normoglycemic mice, with a 3.0-fold increase (p < 0.05) at the aortic sinus and a 3.5-fold increase (p < 0.05) in en face aortas. However, in hyperglycemic mice, castration attenuated atherosclerosis in en face aortas. Supplementation with exogenous DHT led to increased atherosclerosis in hyperglycemic mice and was associated with significant cardiac-related mortality in 21–24-week-old hyperglycemic mice. Conclusions: In this mouse model, while testosterone/DHT may offer cardioprotective benefits under normoglycemic conditions, it appears to exert substantial harmful effects, such as promoting atherosclerosis and increasing the risk of myocardial infarction, in hyperglycemic conditions.

Endocrines doi: 10.3390/endocrines5040044

Authors: Ilham Farhat Vivian L. Chin

Background: Endothelial dysfunction (ED), an early indicator of atherosclerosis, is a well-established predictor of cardiovascular disease. This study investigates ED in children with rare genetic variants linked to obesity and explores the prevalence of these variants in pediatric obesity. Methods: Under an IRB-approved protocol, 54 pediatric patients with severe obesity (BMI ≥ 97%) were screened using the Rhythm® Genetics Test panel between 2021 and 2024 through the Uncovering Rare Obesity® program. This clinically approved buccal test targets 79 genes and one chromosomal region. ED was measured using EndoPAT® (Itamar Medical Ltd by Zoll US based company) in 24 of these patients with related gene variants and compared to controls. Results: Genetic screening: Among the 54 patients screened, 42 (78%) had positive genetic variants, including 18 males and 24 females. The most common variants were PCNT (n = 9), BBS (n = 9), SEMA3 (n = 8), ALMS1 (n = 6), SDCCAG8 (n = 5) and MC4R (n = 5). Endothelial dysfunction: Included 21 subjects with a mean age of 12 years and a mean BMI of 33.31 kg/m². The mean RHI for patients with the PCNT variant was significantly higher (1.34, p = 0.02) compared to controls, but no significant differences were observed for other variants, including BBS, ALMS1, and SH2B1. Conclusions: In this small pilot study, no significant difference in ED was found between children with or without genetic variants, except for PCNT, which showed a higher RHI. Targeted genetic screening revealed 78% with identified pathogenic variants like MC4R, which can clinically guide therapy. Further research is needed to investigate ED in children with obesity variants.

Endocrines doi: 10.3390/endocrines5040043

Authors: Ariadni Spyroglou Panagiota Konstantakou Konstantinos Iliakopoulos Vasiliki Themelidi Dorothea Tsekoura Denise Kolomodi Georgios Kyriakopoulos Pantelis Antonakis Konstantinos Bramis Achilles Chatziioannou George Mastorakos Manousos M. Konstadoulakis Krystallenia I. Alexandraki

Background: Osteoporotic fractures are a common clinical sign of Cushing syndrome (CS). However, Cushing diagnosis can occur years after this clinical manifestation. Methods: Herein, we present the case of a 45-year-old woman who was referred to our department for further diagnosis and treatment. Results: The patient was already under treatment for arterial hypertension and osteoporosis and was recently diagnosed with dyslipidemia and type 2 diabetes. She reported several previous fractures starting already 8 years before presentation. An adrenal CS was diagnosed, and the patient was treated with laparoscopic adrenalectomy, with a subsequent complete remission of her hypercortisolism. This case report presenting a particularly long time gap between initial osteoporosis signs and the final diagnosis underlines the need for an investigation into secondary osteoporosis in low-energy fractures also in the peripheral skeleton. In this context, we performed a literature review, including case reports with fragility fractures that were attributed to endogenous CS. Conclusions: In summary, a delayed diagnosis of CS in patients with a previous accumulation of such fractures is a worrisome observation and should be considered in everyday clinical practice in order to improve the timely diagnosis and treatment of CS.

Endocrines doi: 10.3390/endocrines5040042

Authors: Luciano Pirola Karolina Górecka Carol Gois Leandro Aneta Balcerczyk

Background: The ketogenic diet (KD), characterized by high-fat content, virtually no carbohydrates, and adequate protein intake, induces a metabolic state resembling fasting, as the absence of carbohydrates forces the body to rely on the energetic supply from hepatically produced ketone bodies using free fatty acids as substrate. While the KD is clinically used in pharmacologically refractory epilepsy and specific genetic conditions such as GLUT1 deficiency, recent research suggests that, due to its “fasting mimicking” properties, the KD may also beneficially affect obesity and obesity-associated metabolic diseases. Results: Here, we present a narrative review discussing completed and ongoing nutritional studies in human volunteers specifically addressing the potential of the ketogenic diet as an anti-obesity approach and, from a larger perspective, as an intervention to ameliorate the metabolic state in conditions such as type 1 and 2 diabetes and polycystic ovary syndrome (PCOS). Published studies as well as ongoing clinical trials will be discussed. Efficacy and safety considerations will be discussed, as well as the potential physiological mechanisms mediating the effects of the KD in humans in the context of the (i) energy balance model (EBM) and (ii) carbohydrate–insulin model (CIM) of body weight control. Conclusion: Ketogenic diets may be beneficial to attenuate obesity and improve obesity-related metabolic disease, and here, we try, based on current evidence, to define the boundaries of the KD’s nutritional and clinical usefulness.

Endocrines doi: 10.3390/endocrines5040041

Authors: Cory DeClue Matthew Gonzalez Anna Beth Bradley Barbara G. Carranza-Leon Gitanjali Srivastava

Over the past few years, we have witnessed many advances in the understanding of diabetes and its management. Greater insight into pathogenesis has led to the approval of the first immunopreventative therapy for T1DM. We are using non-insulin agents more for nephro- and cardioprotection than glucose-lowering effects while leaning on advancing technology to use insulin more safely. We now recognize that over half of T1DM is diagnosed in adulthood, the prevalence of obesity in patients with T1DM matches that of the general population, and rates of pediatric T2DM have dramatically risen amongst marginalized youths in recent years. Diabetes is now considered more of a heterogenous disease state than ever before, and practitioners will need to be familiar with these endotypes as personalized medicine replaces standardized treatment approaches. To this end, this article aims to summarize recent findings in an easily digestible manner so that providers may be more familiar with this ever-growing complex disease state.

Endocrines doi: 10.3390/endocrines5040040

Authors: Luis Fernando Schütz Isadora M. Batalha

Background: Granulosa cells are somatic cells within the ovarian follicle. As the primary site of estradiol production, they are critical regulators of several aspects of female reproduction. This review aims to provide an overview of the physiology of mammalian granulosa cells and their importance for female fertility. Methods: the literature about the function and regulation of granulosa cells was reviewed. Results: a comprehensive summary and discussion of the role of granulosa cells on ovarian steroidogenesis and folliculogenesis, as well as factors that control granulosa cells function, are presented. Conclusion: The functions of granulosa cells are regulated by a plethora of intra- and extra-ovarian factors via autocrine, paracrine, and endocrine pathways, which creates a complex regulatory network. A comprehensive understanding of granulosa cells’ physiology is vital for the development of innovative strategies to enhance reproductive outcomes in several species.

Endocrines doi: 10.3390/endocrines5040039

Authors: Lucas Fornari Laurindo Francine Cruz Camargo Alessandra Perfeito Bruno Benedito Ciano Clara Tainá Coelho Gleice Assis Apolinário Isabela do Nascimento Vicentin Jéssica Cambui Andreasi Beatriz Leme Boaro Ricardo José Tofano Cláudia Rucco Penteado Detregiachi Jesselina Francisco dos Santos Haber Sandra Maria Barbalho Lance Alan Sloan Kátia Portero Sloan Antonelly Cassio Alves de Carvalho Marie Oshiiwa Patrícia Cincotto dos Santos Bueno Tereza Laís Menegucci Zutim Rebeca Maria Siqueira da Silva Eduardo Federighi Baisi Chagas Marcelo Dib Bechara Karina R. Quesada

Background: The visceral adiposity index (VAI) is a composite marker designed to quantify visceral adiposity and its metabolic implications. It integrates anthropometric (such as waist circumference and BMI) and metabolic parameters (including triglyceride levels and HDL cholesterol), providing a more comprehensive assessment of visceral fat distribution than traditional measures alone. Higher VAI values are indicative of increased visceral adiposity and have been linked to heightened cardiovascular risk and metabolic disturbances. In recent years, understanding the complex interplay between metabolic factors and cardiovascular health has become increasingly important. Methods: This cross-sectional study delves into the influence of neck circumference (NC), blood pressure (BP), C-reactive protein (CRP), and insulin resistance on the VAI among outpatient cardiology patients, offering insights into sex-specific disparities and the utility of VAI as a diagnostic tool for assessing visceral adiposity and associated cardiovascular risks. Results: The sample comprised 268 outpatient cardiology patients (152 men, 116 women). Men, averaging 55.4 years old (SD = 14.4), exhibited significantly higher VAI values than women, with robust correlations found between VAI and markers of insulin resistance (Insulin: ρ = −0.167, p = 0.006; HOMA-IR: ρ = −0.163, p = 0.007). Analysis across VAI quartiles highlighted distinct patterns, revealing lower NC and elevated systolic blood pressure (SBP) values in higher VAI categories. Despite these associations, multiple linear regression controlling for age and sex demonstrated a limited predictive capacity of NC, BP, CRP, and lipid profiles on VAI (R2 range: 0.001–0.011). Conclusions: These findings underscore sex-specific disparities and suggest that VAI serves as a modest yet valuable tool in assessing visceral adiposity and associated cardiovascular risks.

Endocrines doi: 10.3390/endocrines5040038

Authors: Atsushi Hattori Maki Fukami

Precocious puberty (PP) requires appropriate management to prevent short adult height, psychosocial issues, and other adverse outcomes. Genetic diagnosis potentially improves the management of PP. Pathogenic NR0B1 variants, which typically cause X-linked adrenal hypoplasia congenita, can also affect gonadal function. While boys with NR0B1 variants usually exhibit hypogonadotropic hypogonadism during adolescence, previous reports have suggested that minipuberty, a physiological transient activation of the hypothalamic–pituitary–gonadal axis during infancy, occurs in these patients and can persist beyond a typical duration. In rare cases, NR0B1 variants cause PP. PP associated with NR0B1 variants has unique features such as early onset and high serum testosterone levels that are often disproportionate to testicular size. Three underlying mechanisms have been proposed for the association between PP and NR0B1 variants: (1) adrenocorticotropic hormone (ACTH)-dependent, (2) gonadotropin-dependent, and (3) ACTH- and gonadotropin-independent mechanisms. The factors contributing to PP vary among cases. Determining the underlying mechanisms is crucial for adopting appropriate therapeutic strategies to control PP. However, as the detailed molecular networks mediating these mechanisms are largely unclear, further research is needed to pave the way for a more effective and personalized management of patients with PP associated with NR0B1 variants.

Endocrines doi: 10.3390/endocrines5040037

Authors: Jelena Bogdanovic Kaitlin Freeman Chadwick Brown Rachel Singleton Millie Behera Jeanne E. O’Brien Edward Zbella Robert H. Christenson

Background: Serum anti-Müllerian hormone (AMH) levels and antral follicle count are key in evaluating ovarian reserve (OR) for fertility. The performance of the Siemens Healthineers AMH assay was assessed on the ADVIA Centaur® System. Methods: Analytical characteristics, clinical performance, and method comparison studies were performed in a prospective cohort of 532 women at fertility clinics. Serum AMH levels were determined using ADVIA Centaur, Beckman Access®, and Roche Elecsys® assays. Results: The limit of quantitation for the ADVIA Centaur AMH assay was 0.030 ng/mL. Repeatability was ≤2.9% CV, within-lab repeatability was ≤3.2% CV, and reproducibility was ≤4.4% CV. Results using serum or lithium heparin sample types were equivalent. Diagnostic sensitivity across assays ranged from 77.3% to 90.2% and specificity ranged from 51.0 to 71.0%; corresponding positive and negative predictive values ranged from 66.6% to 74.3% and 74.2% to 83.0%, respectively. Receiver operating characteristic analyses demonstrated that the assays have a high probability for discriminating between diminished–normal and high OR. ADVIA and Beckman assays agreed according to ADVIA = 1.00 × Beckman + 0.014 ng/mL, τ = 0.909, while a more modest correlation of ADVIA = 1.41 × Roche − 0.024 ng/mL, τ = 0.777 was observed with Roche assay. Conclusions: The ADVIA Centaur assay demonstrates acceptable analytical characteristics and clinical performance comparable to the Roche AMH assay and is essentially interchangeable with the Beckman AMH assay for reliable OR assessment.

Endocrines doi: 10.3390/endocrines5040036

Authors: Nuha Ahmad Dsouki Bruno Fiorelini Pereira Roberta Goes da Silva Vinicius Gonçalves Rodrigues Rafaella da Silva Brito Marina Malta Letro Kizys Maria Izabel Chiamolera Rui Monteiro Maciel Caroline Serrano-Nascimento Gisele Giannocco

Introduction: During the formation of neural circuits, the developing brain demonstrates extraordinary plasticity, heavily influenced by hormones. These chemical messengers interact with specific receptors to regulate vital physiological functions. The thyroid gland plays a pivotal role in maintaining hormonal balance and guiding brain development. However, emerging threats like endocrine-disrupting chemicals (EDCs) can interfere with this intricate system. EDCs are exogenous substances that can mimic, enhance, or block the actions of endogenous hormones, disrupting hormonal signaling in the brain at various developmental stages. Exposure can impair cognitive function and behavior due to disruptions in thyroid function. Studies indicate that mixtures of EDCs negatively impact brain development, leading to lower IQ and behavioral problems. Reducing EDC exposure through regulations and public awareness is crucial, and further research is needed to elucidate their mechanisms. Conclusions: Protecting vulnerable populations, such as pregnant women and children, is essential through prompt regulatory measures.

Endocrines doi: 10.3390/endocrines5040035

Authors: Alexandra M. Bodnaruc Mathilde Roberge Isabelle Giroux Céline Aguer

Background/Objectives: There is a bidirectional relationship between major depressive disorder (MDD) and type 2 diabetes (T2D), as MDD increases the risk of T2D by 38% to 67%, and T2D increases the risk of MDD by 15% to 33%. Many factors contribute to the occurrence of comorbid MDD and T2D, including converging pathophysiological pathways like inflammation. The objective of this review was to comprehensively summarize available evidence on the relationship between MDD, T2D, and inflammation. Results: Although the precise mechanisms linking T2D and MDD are still not fully understood, shared inflammatory mechanisms likely contributes to the heightened risk of developing this comorbidity. To date, the evidence supports that chronic low-grade inflammation is a feature of both MDD and T2D and has been shown to interact with pathways that are relevant to the development of both chronic disorders, including the hypothalamic–pituitary–adrenal (HPA) axis, neuroplastic processes, gut microbiome, insulin resistance, and adipose tissue dysfunction. Through their impact on inflammation, dietary and physical activity interventions can play a role in the risk and management of MDD and T2D. Conclusions: Deepening our understanding of the mechanisms underlying the augmented inflammatory responses observed in individuals with the MDD and T2D comorbidity is essential for tailoring appropriate therapeutic strategies.

Endocrines doi: 10.3390/endocrines5040034

Authors: Riccardo Calafiore Giovanni Luca Francesco Gaggia Giuseppe Basta

Background: T1D is a severe metabolic disorder due to selective autoimmune pancreatic islet β-cell killing, which results in complete abrogation of endogenous insulin secretion. The affected patients, once the disease is clinically overt, must immediately undertake insulin supplementation according to intensive therapy regimens to prevent the onset of acute and chronic complications, some of them potentially lethal. Replacement of the destroyed β-cells with fresh and vital pancreatic endocrine tissue, either of the whole organ or isolated islets transplantation, started a few decades ago with progressively encouraging results, although exogenous insulin withdrawal was obtained in a minor cohort of the treated patients. The restricted availability of donor organs coupled with general immunosuppression treatment of recipients to avoid graft immune rejection may, at least partially, explain the limited success achieved by these procedures. Results: The introduction of pluripotent stem cells (either of human embryonic origin or adult cells genetically induced to pluripotency) that can be differentiated toward insulin secretory β-like cells could provide an indefinite resource for insulin-producing cells (IPCs). Conclusions: Because the use of human embryos may encounter ethical problems, employment of adult multipotent mesenchymal stem cells (MSCs) extracted from several tissues may represent an alternative option. MSCs are associated with strong immunoregulatory properties that can alter early stages of β-cell-directed autoimmunity in T1D, other than holding the potential to differentiate themselves into β-like cells. Lights and shadows of these new strategies for the potential cure of T1D and their advancement state are reviewed.

Endocrines doi: 10.3390/endocrines5030033

Authors: Sofia Guerreiro Mariana Mourão Isabel Loureiro Rosário Eusébio Sule Canberk Hugo Pinto Marques

Introduction: Thyroid nodules are extremely common and require complex management to prevent unnecessary surgical intervention and ensure that no malignant disease is overlooked. Several diagnostic tools and scoring systems are available to evaluate the risk of malignancy (ROM). The goal is to assess variables that can aid and support the clinical recommendations suggested by the updated Bethesda System for Reporting Thyroid Cytopathology (TBSRTC-2023), such as the ultrasonographic features of thyroid nodules, particularly for the indeterminate categories III (atypia of undetermined significance) and IV (follicular neoplasm). Methods: We retrospectively analysed the correlation of the demographic and ultrasonographic characteristics of thyroid nodules with the cytopathological and histopathological diagnoses of TBSRTC categories III (atypia of undetermined significance), IV (follicular neoplasm), V (suspicious for malignancy), and VI (malignant) in patients who underwent surgery in a single Portuguese centre over a 10-year period. Results: In total, 360 nodules were evaluated in 341 patients, and 57% were histopathologically malignant or borderline. The majority were included in the TBSRTC indeterminate categories III and IV, with ROMs of 44% and 43%, respectively. The ultrasonographic characteristics associated with a higher TBSRTC category and a greater ROM value were hypoechogenicity, the presence of microcalcifications, irregular margins, and the presence of cervical adenopathy. When correlating with a malignant histology, only adenopathy and the presence of microcalcifications were observed to be statistically significant. Discussion: The indeterminate categories of the TBSRTC have been the most challenging ones to manage. The new TBSRTC (2023) guidelines, as well as the ultrasonographic characteristics of a patient’s nodule, can be helpful in assessing the ROM and deciding on an appropriate course of treatment. Other resources, such as molecular tests, are also playing a more important role in the clinical decision process and may become crucial in the future. Conclusions: The worrisome ultrasound features that this study found to statistically correlate with a malignant histology were the presence of microcalcifications and adenopathy. The clinical management of thyroid nodules requires a careful analysis of clinical history and an evaluation of demographic details, personal and family history, ultrasonographic features, and the results of cytopathology, thyroid function, and molecular/genetic tests.

Endocrines doi: 10.3390/endocrines5030032

Authors: Vinicius Gonçalves Rodrigues Guilherme Henrique Érica Kássia Sousa-Vidal Rafaela Martins Miguel de Souza Evelyn Franciny Cardoso Tavares Nathana Mezzalira Thacila de Oliveira Marques Bruna Monteiro Alves João Anthony Araújo Pinto Luana Naomi Niwa Irikura Renata Elen Costa da Silva Kelly Cristina de Oliveira Rui Monteiro de Barros Maciel Gisele Giannocco Caroline Serrano-Nascimento

Endocrine-disrupting chemicals (EDCs) are synthetic or natural compounds that interfere with the endocrine system, inducing harmful effects on organisms depending on the dose and period of exposure. Numerous studies have identified concerning amounts of EDCs in environmental and human samples. The thyroid gland is essential for thyroid hormone production and controls several body functions. Several EDCs have been classified as thyroid disruptors, impairing thyroid hormone production, synthesis, metabolism, transport, and/or actions. Notably, thyroid disorders are the second most prevalent endocrine disease worldwide, with incidence increasing significantly in recent years. Some studies have correlated this rise in thyroid dysfunctions and cancers with increased exposure to EDCs. Although many EDCs are linked to thyroid dysfunction, this review focuses on the deleterious effects of plasticizers, organochlorine pesticides, and per- and poly-fluoroalkyl substances on thyroid function. These contaminants are commonly found in food, water, and everyday products. Although the impact of human exposure to these EDCs is controversial, numerous epidemiological, in vivo, and in vitro studies have indicated their harmful effects on thyroid function. Given the critical role of thyroid function and hormone production in growth, metabolism, and development, this review summarizes the consequences of exposure to thyroid disruptors for human health.

Endocrines doi: 10.3390/endocrines5030031

Authors: Bianca de Almeida-Pititto Julia Ines Branda Julia M. de Oliveira Patrícia M. Dualib Luisa Bittencourt de Aquino Fernandes Dias Isabela M. Bensenor Paulo A. Lotufo Sandra Roberta G. Ferreira

Background: Type 2 diabetes mellitus (DM) is an important disease with an impact on public health globally. Early assessment is necessary with accessible markers, such as the TG/HDL ratio, in predicting DM. Methods: A total of 11,653 subjects from the ELSA-Brazil were included in this analysis and were reevaluated after 3.9 ± 0.6 years of follow-up. Participants were classified according to the quartiles of the TG/HDL index, stratified by sex. ANOVA with Bonferroni correction and p-for-trend analysis were used to compare groups. Cox analysis was performed with adjustments for covariables. Kaplan–Meier curves are presented with the log rank pool and linear analysis. Results: From 11,653 participants (56% female; aged 50.5 ± 8.7 years), 866 (7.8%) were diagnosed with DM (7.2% in women and 7.8% in men). For both sexes, a worsening of the cardiometabolic profile was observed across the increase in TG/HDL quartiles (p < 0.001). Incidence rates of DM increased across TG/HDL quartiles for both men (from Q1 3.3% to Q4 12.8%) and women (from Q1 3.3% to Q4 12.4%). For the entire period, the incidence was highest in participants in the fourth quartile of TG/HDL (log rank analysis < 0.001 for both sexes). In the Cox regression analyses, for men, the HR (95%CI) for risk of DM was 2.4 (1.49–3.26) across the fourth quartile of the TG/HDL ratio, and in women it was 1.57 (1.11–2.22) for the third quartile and 2.08 (1.48–2.93) for the fourth quartile, compared to the first quartile after adjustments. Conclusions: Higher levels of the TG/HDL ratio were independently predictors of DM in both men and women.

Endocrines doi: 10.3390/endocrines5030030

Authors: Gaspare Alfì Danilo Menicucci Dalì Antonia Ciampa Vito Di Giura Giulia Marconcini Claudio Urbani Fausto Bogazzi Angelo Gemignani

Acromegaly is a rare endocrine syndrome characterized by unrestrained growth hormone (GH) secretion from a GH-secreting pituitary neuroendocrine tumor (PitNET). Data on sleep disorders are scanty and mainly linked to Obstructive Sleep Apnea Syndrome (OSAS). This study aimed to evaluate the prevalence of insomnia and sleep quality in a cohort of patients with a low risk of OSAS before and after therapies for acromegaly. A total of 27 naïve acromegalic patients (mean age 55.15 ± 10.53 years) were submitted to a psychometric sleep evaluation and compared to a matched control group of 24 Non-Functioning Pituitary micro-Adenoma patients (mean age 51.08 ± 11.02 years). A psychometric sleep evaluation was carried out 4 years later, after achieving acromegaly control in all patients. The role of different therapies for acromegaly (somatostatin analogues, pegvisomant, or adenomectomy) was evaluated. At the initial evaluation, most untreated acromegalic patients had a higher rate of impaired sleep quality and clinical insomnia than NFPA patients (p = 0.001 ES = 1.381, p = 0.001 ES = 1.654, respectively). Patients treated with somatostatin analogues or pituitary adenomectomy had an improvement in insomnia parameters (p = 0.046 ES = 0.777, p = 0.038 ES = 0.913, respectively). Conversely, in patients treated with pegvisomant, sleep quality and insomnia worsened (p = 0.028 ES = 1.002, p = 0.009 ES = 1.398, respectively). In summary, therapies for acromegaly seem to have divergent effects on perceived sleep disorders. Concerning sleep, somatostatin analogues and adenomectomy seem to have favorable effects on the psychometric parameters of sleep.

Endocrines doi: 10.3390/endocrines5030029

Authors: Antonio Gangemi Paolo Bernante

Background: The prevalence of type 2 diabetes mellitus (T2DM) has been steadily increasing over the past few decades, largely due to the rise in obesity rates. Bariatric surgery is a gastrointestinal surgical treatment focused on achieving weight loss in individuals with obesity. A more recent and growing body of literature has shown that improvements in glycemic control and insulin sensitivity and even the remission of T2DM can be seen in patients with obesity and T2DM (“diabesity”), before significant weight loss is achieved, justifying the modification of the terminology from bariatric to metabolic and bariatric surgery (BMS). Main Results: This narrative review provides an overview of the latest literature on BMS for diabesity, discussing key publications and exploring controversial and diverging hypotheses. Robust scientific evidence supporting the use of BMS as a treatment for diabesity has been garnered and new venues are being explored, suggesting the novel and complementary role of the latest generation of incretin-based pharmacotherapy. Conclusions: BMS has emerged as a valuable treatment option for patients with diabesity, offering significant improvements in glycemic control, weight loss, and overall health. The limitations of the currently available and reviewed literature include the flawed knowledge of the mechanisms of action and long-term effects of BMS for the treatment of diabesity. Further studies are also warranted to refine the patient selection criteria and optimal surgical techniques and to evaluate the impact of surgery on T2DM outcomes in diverse populations. Lastly, there is a scarcity of studies investigating the efficacy of BMS against incretin-based pharmacotherapy. The non-systematic, narrative nature of this review and its implicit subjective examination and critique of the body of literature are to be considered additional and intrinsic limitations.

Endocrines doi: 10.3390/endocrines5030028

Authors: Taylor Downs Fabricio da Silva Costa Cristiane de Freitas Paganoti Olivia J. Holland Deanne H. Hryciw

During pregnancy, the adipokines leptin and adiponectin can affect placental nutrient transport and inflammatory pathways, potentially leading to altered fetal growth and pregnancy complications including gestational diabetes mellitus (GDM) and preeclampsia (PE). The aim of this systematic review is to gather and analyze research on maternal circulating leptin and adiponectin levels and their relationship to adverse pregnancy and birth outcomes. Additionally, it seeks to determine whether these hormones are linked to alterations in placental transporters and cell signaling pathways. PubMed and MEDLINE were systematically searched to include studies published between 2012 and 2022. All primary data studies reporting serum adiponectin and/or leptin, placental mRNA and protein levels of related transporters, and adverse birth outcomes were eligible. The current systematic review encompasses a total of 14 articles. Abnormal serum maternal leptin and adiponectin levels were associated with changes in fetal growth and placental cellular signaling and nutrient transporters. A majority of studies associated elevated maternal leptin and reduced adiponectin with fetal overgrowth, although this relationship was not consistent and may be complicated when other pathologies are present. The effects of maternal leptin and adiponectin on fetal growth may be driven by placental adaptation in nutrient transporters and mitochondria. Future studies should determine if the placental effects of leptin and adiponectin that have been found in models have mechanistic roles in human pregnancy.

Endocrines doi: 10.3390/endocrines5030027

Authors: Sawyer Ashcroft Noura S. Dosoky William N. Setzer Prabodh Satyal

Endocrine disruptors are molecules that can interfere with the proper functioning of the endocrine system and lead to harmful effects in living organisms. This review focuses on the impact of synthetic fragrances, which are commonly found in personal care and household products, on the endocrine system. The article discusses the different types of hormones in the body and how they interact with receptors to produce signals. It also explores how endocrine disruptors can interfere with hormone signaling and transport, leading to adverse effects in the body. This work underscores the crucial need for further research into the impact of synthetic fragrances on the endocrine system and the importance of using safer alternatives in personal care and household products.

Endocrines doi: 10.3390/endocrines5030026

Authors: Haruko Yokosuka

Dysmenorrhea treatment with 0.5 mg dienogest tablets twice daily (1 mg/day) has proven useful, but its effect on premenstrual disorders has not yet been evaluated. This study aimed to evaluate the efficacy of 0.5 mg dienogest tablets in relieving premenstrual syndrome (PMS)-like symptoms during the treatment of dysmenorrhea in comparison with that of continuous low-dose estrogen–progestin (LEP/COC) drospirenone/ethinylestradiol combination, which is considered effective in treating premenstrual dysphoric disorder. During the standard course of dysmenorrhea treatment with dienogest or LEP/COC, PMS-like symptoms were scored based on patients’ reports, and the treatment effects were compared. As a result, the dienogest group experienced a significant improvement in PMS-like symptoms compared with the LEP/COC group over the 6-month study period (p < 0.01). Furthermore, dienogest was more effective in providing relief from PMS-like symptoms, with 89.7% of patients reporting a complete resolution of PMS-like symptoms at 6 months, compared with 47.1% in the LEP/COC group (p < 0.01). These results indicate that dienogest is effective in relieving PMS-like symptoms, similar to LEP/COC. Further studies are needed to determine whether 0.5 mg dienogest tablets, which are only available in Japan, are effective in treating premenstrual disorders diagnosed via standard methods.

Endocrines doi: 10.3390/endocrines5030025

Authors: Anastasia Ibba Chiara Guzzetti Lavinia Sanfilippo Sandro Loche

Growth hormone deficiency (GHD) is the most frequent pituitary hormone deficiency in childhood, with an incidence of 1 in 4000–10,000 live births. GHD can be congenital (genetic or due to hypothalamic/pituitary abnormalities) or acquired and can be isolated (IGHD) or associated with other pituitary hormone deficiencies, but most cases are idiopathic. GH stimulation testing is commonly used in the diagnostic workup of GHD, except for some clinical conditions that do not require GH stimulation tests for the diagnosis. Children with GHD receive replacement therapy with daily injections of recombinant human GH (rhGH). RhGH therapy is effective in increasing short-term height gain and adult height in patients with GHD. The safety of long term GH therapy has been confirmed in many large international studies. Recently, long-acting weekly GH formulations have been introduced, showing good efficacy and safety profiles.

Endocrines doi: 10.3390/endocrines5030024

Authors: Paola Chiarello Giuseppe Seminara Sabrina Bossio Valentina Rocca Emma Colao Rodolfo Iuliano Antonio Aversa

Adult-onset cases of idiopathic hypogonadotropic hypogonadism (IHH) are characterized by partial or normal puberty development until adolescence and by the impairment of the hypothalamic–pituitary–gonadal (HPG) axis in adulthood. WDR11 and DCC genes are known to be involved in axonal development, particularly of hypothalamic GnRH neurons, and ciliogenesis. We report a female case of adult-onset hypogonadism and cerebellar ataxia, in which we identified two gene mutations. A panel of 48 genes was set up to search for variants in the causative genes of CHH. The variants found were analyzed following the American College of Medical Genetics and Genomics (ACMG) criteria to define their pathogenicity. We identified a missense heterozygous variant in the WDR11 gene NM_018117.12:c.2306T>G (p.Met769Arg) and a mutation in a second gene DCC resulting in amino acid substitutions NM_005215.4:c.3533C>T (p.Ser1178Phe). These variants were classified as being of uncertain clinical significance. We assume that there is a link between the variants found and the impairment of the gonadotrophic and neurological phenotype of the patient. Therefore, we propose the genetic test to identify the best therapeutic approach to identify infertility in female patients with IHH; we believe it is necessary to test WDR11 and DCC genes in larger populations with the same condition to introduce it in future protocols of assessment.