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Keywords = hypothyroid metabolic status

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14 pages, 503 KB  
Article
Recreational Exercise and Inflammatory Patterns in Hashimoto’s Thyroiditis: Observations from a Cross-Sectional Study
by Marko Vuletić, Vanna Žnidar, Ana Barić Žižić, Sanda Sladić, Dean Kaličanin, Vesela Torlak Lovrić, Maja Cvek, Ante Punda and Vesna Boraska Perica
Biomolecules 2025, 15(11), 1510; https://doi.org/10.3390/biom15111510 - 25 Oct 2025
Viewed by 623
Abstract
In this cross-sectional observational study, we investigated whether recreational exercise (RE) influences systemic inflammation in Hashimoto’s thyroiditis (HT) across different disease severity groups. We analyzed 403 participants from the Croatian Biobank of Patients with HT (CRO-HT), including 173 controls and 230 HT patients [...] Read more.
In this cross-sectional observational study, we investigated whether recreational exercise (RE) influences systemic inflammation in Hashimoto’s thyroiditis (HT) across different disease severity groups. We analyzed 403 participants from the Croatian Biobank of Patients with HT (CRO-HT), including 173 controls and 230 HT patients (euthyroid, levothyroxine [LT4]-treated, and hypothyroid). Serum levels of 92 inflammatory proteins were measured using the Olink® Target 96 Inflammation panel, and exercise status was assessed via structured questionnaires. Linear regression revealed distinct protein associations depending on thyroid status. In controls, RE was associated with reduced MMP-10 and FGF-5, reflecting cardiovascular and muscle benefits. In euthyroid patients, RE was associated with decreased CXCL9 and TRAIL, implicating reduced type 1 inflammation and vascular risk. LT4-treated patients showed increases in IL-15RA and IL-24 with RE, suggesting improved muscle metabolism and anti-inflammatory effects. In hypothyroid patients, RE was associated with reduced CCL20 and increased HGF, while changes in TRANCE and TWEAK indicated mixed effects on bone and immune regulation. Notably, RE was associated with reduced CXCL9 and CCL20, two proteins previously linked to HT risk. Overall, RE is associated with distinct changes in inflammatory profiles across HT disease severity groups, with the most favourable responses observed in LT4-treated patients, suggesting synergy with hormone therapy. Full article
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15 pages, 255 KB  
Article
Antioxidant Capacity of Colostrum of Mothers with Gestational Diabetes Mellitus—A Cross-Sectional Study
by Paulina Gaweł, Karolina Karcz, Natalia Zaręba-Wdowiak and Barbara Królak-Olejnik
Nutrients 2025, 17(21), 3324; https://doi.org/10.3390/nu17213324 - 22 Oct 2025
Viewed by 409
Abstract
Background: Women with gestational diabetes mellitus (GDM) are vulnerable to oxidative stress, yet limited data exist on the antioxidant potential of their breast milk. This study aimed to evaluate the antioxidant capacity and basic composition of colostrum in women with GDM compared to [...] Read more.
Background: Women with gestational diabetes mellitus (GDM) are vulnerable to oxidative stress, yet limited data exist on the antioxidant potential of their breast milk. This study aimed to evaluate the antioxidant capacity and basic composition of colostrum in women with GDM compared to healthy controls, focusing on total antioxidant capacity (TAC) and enzymatic antioxidants: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Methods: The study included 77 lactating mothers: 56 with gestational diabetes (15 managed with diet/exercise—GDM G1; 41 required insulin—GDM G2) and 21 healthy controls. Colostrum samples were collected on days 3–5 postpartum and analyzed for macronutrients and antioxidant enzymes. To enable comparisons across study groups and to explore associations with maternal characteristics, a range of statistical methods was applied. A taxonomic (classification) analysis was then performed using the predictors that best fit the data: study group membership, maternal hypothyroidism history (from the medical interview), and gestational weight gain. Results: TAC was significantly lower in the GDM G2 group compared to GDM G1 and controls (p = 0.001), with no differences in enzymatic antioxidants. The control group had the highest energy (p = 0.048) and dry matter content (p = 0.015), while protein, fat, and carbohydrate levels did not differ significantly. After dividing the study group into four clusters, based on maternal health factors, including GDM status and thyroid function, TAC levels differed significantly between clusters, with the highest values observed in Cluster 3 (healthy controls without thyroid dysfunction) and the lowest in Cluster 2 (GDM and hypothyroidism). Analysis of colostrum composition revealed significant differences in energy content (p = 0.047) and dry matter concentration (p = 0.011), while no significant differences were found in other macronutrients. Conclusions: Our findings suggest that maternal metabolic and endocrine conditions, such as GDM and thyroid dysfunction, may differentially influence the nutritional and functional properties of colostrum—particularly its antioxidant potential. Full article
(This article belongs to the Special Issue Maternal and Child Nutrition: From Pregnancy to Early Life)
24 pages, 920 KB  
Article
Intersecting Endocrine Pathways in Cardiomyopathy: The Role of Metabolic Burden in Structural Heart Disease
by Ovidiu Țica, Mircea Ioan Șandor, Anca Huniadi, Cristian Daina, Sanda Monica Filip, Ilarie Brihan, Monica Sabău, Ioana Zaha and Otilia Țica
Biomedicines 2025, 13(10), 2364; https://doi.org/10.3390/biomedicines13102364 - 26 Sep 2025
Cited by 1 | Viewed by 458
Abstract
Background: Dilated cardiomyopathy (DCM) is a major contributor to heart failure-related morbidity and mortality. While type 2 diabetes mellitus (T2DM), obesity, and thyroid dysfunction are individually linked to cardiovascular disease, their combined effects on DCM remain poorly understood. Objective: To evaluate the independent [...] Read more.
Background: Dilated cardiomyopathy (DCM) is a major contributor to heart failure-related morbidity and mortality. While type 2 diabetes mellitus (T2DM), obesity, and thyroid dysfunction are individually linked to cardiovascular disease, their combined effects on DCM remain poorly understood. Objective: To evaluate the independent and synergistic associations of diabetes (stratified by treatment), thyroid dysfunction, and obesity with the prevalence of DCM and 30-day hospital readmission. We further examined the utility of a composite Metabolic Burden Score for risk stratification. Methods: In this retrospective cohort study, electronic health record data from 1079 adult patients at a tertiary care center were analyzed. Multivariable logistic regression, including ridge regularization, was used to identify predictors of DCM. Endocrine phenotypes were stratified by diabetes and thyroid status. A Metabolic Burden Score (range: 0–3) based on diabetes, obesity, and thyroid dysfunction was developed and correlated with clinical outcomes. Results: DCM was diagnosed in 46% of the cohort. Non-insulin-treated diabetes (OR: 6.93; 95% CI: 3.78–12.73), hypothyroidism (OR: 1.78; 95% CI: 1.02–3.11), and male sex (OR: 2.33; 95% CI: 1.36–4.00) were independently associated with increased DCM risk. Obesity was not independently predictive but contributed to DCM prevalence when assessed within the Metabolic Burden Score. DCM prevalence increased across burden strata, reaching 50% in the high-risk group. Notably, the moderate-risk group had the highest 30-day readmission rate (42.8%). Conclusions: Non-insulin-treated diabetes and hypothyroidism are key metabolic drivers of DCM. A simple composite burden score offers a clinically useful tool for stratifying risk of DCM and early readmission. These findings support integrated endocrine–cardiac screening strategies to improve early identification and prevention of structural heart disease. Full article
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20 pages, 315 KB  
Article
Determinants of Multi-Organ Morbidity in Neo-Transfusion-Dependent Thalassemia: A Cross-Sectional Analysis
by Antonella Meloni, Paolo Ricchi, Laura Pistoia, Filomena Longo, Valerio Cecinati, Zelia Borsellino, Francesco Sorrentino, Elisabetta Corigliano, Michela Zerbini, Priscilla Fina, Ada Riva, Giuseppe Peritore, Vincenzo Positano and Alberto Clemente
J. Clin. Med. 2025, 14(18), 6602; https://doi.org/10.3390/jcm14186602 - 19 Sep 2025
Viewed by 598
Abstract
Background: This multicenter cross-sectional study aimed to assess the prevalence of vascular, hepatic, cardiac, endocrine, and bone complications and to identify factors associated with their occurrence in adult patients with neo-transfusion-dependent thalassemia (neo-TDT). Methods: A total of 140 adult neo-TDT patients (defined as [...] Read more.
Background: This multicenter cross-sectional study aimed to assess the prevalence of vascular, hepatic, cardiac, endocrine, and bone complications and to identify factors associated with their occurrence in adult patients with neo-transfusion-dependent thalassemia (neo-TDT). Methods: A total of 140 adult neo-TDT patients (defined as receiving >4 transfusions/year; mean age 44.3 ± 12.1 years; 56.4% female) were retrospectively enrolled from the Extension–Myocardial Iron Overload in Thalassemia (E-MIOT) network. Iron overload (IO) was assessed by magnetic resonance imaging and complications were classified according to established clinical criteria. Logistic regression analyses were performed to investigate associations of complications with age, sex, splenectomy status, chelation therapy, hemoglobin < 9 g/dL, ferritin ≥ 1000 ng/mL, and hepatic, pancreatic, and cardiac IO. Results: Complications affecting fewer than 5% of patients—including leg ulcers, cirrhosis, thrombosis, heart failure, and hypoparathyroidism—were excluded from statistical analysis. Bone metabolism disorders were the most prevalent complications (68.6%), followed by impaired glucose metabolism (15.7%). The prevalence of other complications was: extramedullary hematopoiesis (EMH) 19.3%, pulmonary hypertension (PH) 7.1%, arrhythmias 12.1%, hypogonadism 11.4%, and hypothyroidism 15.0%. Male sex was independently associated with EMH (odds-ratio [OR] = 2.67; p = 0.027). Hepatic IO was the only significant predictor of PH (OR = 4.12; p = 0.047). Arrhythmias were strongly associated with older age (OR = 22.67; p < 0.0001), while both older age (OR = 4.42; p = 0.004) and pancreatic IO (OR = 7.40; p = 0.012) were independently associated with impaired glucose metabolism. No significant associations were identified for hypogonadism, hypothyroidism, or bone metabolism disorders. Conclusion: This study offers updated insights into the burden of complications in neo-TDT patients and highlights specific risk factors that may inform comprehensive, multidisciplinary surveillance strategies. Full article
(This article belongs to the Section Hematology)
20 pages, 517 KB  
Review
Nutrition for Children with Down Syndrome—Current Knowledge, Challenges, and Clinical Recommendations—A Narrative Review
by Sebastian Żur, Adam Sokal, Wiktoria Staśkiewicz-Bartecka, Agata Kiciak, Mateusz Grajek, Karolina Krupa-Kotara, Oskar Kowalski and Agnieszka Białek-Dratwa
Healthcare 2025, 13(17), 2222; https://doi.org/10.3390/healthcare13172222 - 4 Sep 2025
Cited by 1 | Viewed by 2062
Abstract
Background/Objectives: Children with Down syndrome (DS) present unique and multifaceted nutritional challenges arising from genetic, metabolic, and developmental factors. Despite growing interest in the health of individuals with DS, dedicated nutritional guidelines tailored to their specific needs remain lacking. This narrative review aims [...] Read more.
Background/Objectives: Children with Down syndrome (DS) present unique and multifaceted nutritional challenges arising from genetic, metabolic, and developmental factors. Despite growing interest in the health of individuals with DS, dedicated nutritional guidelines tailored to their specific needs remain lacking. This narrative review aims to summarize current scientific evidence on nutritional status, challenges, and therapeutic strategies in children with DS, with an emphasis on clinical implications and practical recommendations for healthcare professionals. Methods: A literature search was conducted across four databases (PubMed, Scopus, Web of Science, and Google Scholar) for English-language publications from 1993 to June 2025. Thirty-five peer-reviewed articles were included, comprising original studies, narrative reviews, and expert guidelines (e.g., the American Academy of Pediatrics [AAP], the European Society for Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN], and the European Federation of Associations of Dietitians [EFAD]). The selection process followed the PRISMA protocol. Studies were categorized according to key themes: energy requirements, comorbidities, feeding difficulties, nutrient needs, and therapeutic interventions. Results: Children with DS typically exhibit lower basal metabolic rates and altered body composition (i.e., higher fat mass and reduced lean mass), which increase their risk of both obesity and nutrient deficiencies. Common comorbidities—such as hypothyroidism, celiac disease, and gastrointestinal or immune disorders—further complicate dietary management. Feeding difficulties, including sucking/swallowing impairments, food selectivity, neophobia, and delayed independence in eating, are prevalent and significantly affect diet quality. Key nutrients of concern include protein, omega-3 fatty acids, fiber, vitamins B12 and D, iron, and antioxidants. Although no official nutrition guidelines currently exist for this population, existing recommendations from pediatric and dietetic organizations provide partial guidance that can be adapted to clinical practice. Conclusions: There is an urgent need to develop evidence-based, population-specific dietary guidelines for children with Down syndrome. Clinical nutrition care should be individualized, multidisciplinary, and proactive, integrating regular assessments of growth, feeding abilities, and biochemical markers. Dietitians must play a central role in both early intervention and long-term management. Further research, particularly interventional studies, is essential to optimize dietary strategies and improve health outcomes in this vulnerable population. Full article
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23 pages, 885 KB  
Review
Thyroid Health and Selenium: The Critical Role of Adequate Intake from Fetal Development to Adolescence
by Valeria Calcaterra, Hellas Cena, Ilaria Anna Maria Scavone, Ilaria Zambon, Silvia Taranto, Cecilia Ricciardi Rizzo, Chiara Ferrara, Marianna Diotti and Gianvincenzo Zuccotti
Nutrients 2025, 17(14), 2362; https://doi.org/10.3390/nu17142362 - 18 Jul 2025
Viewed by 7742
Abstract
The thyroid gland plays a crucial role in regulating metabolism and supporting development through the production of the hormones T4 and T3. These hormones are essential during childhood for nervous system myelination, physical growth, puberty, skeletal and dental maturation, and overall metabolic balance. [...] Read more.
The thyroid gland plays a crucial role in regulating metabolism and supporting development through the production of the hormones T4 and T3. These hormones are essential during childhood for nervous system myelination, physical growth, puberty, skeletal and dental maturation, and overall metabolic balance. In early infancy, when the hypothalamic–pituitary–thyroid axis is still immature, thyroid dysfunction can result in a range of long-term complications. The metabolism and action of thyroid hormones depend not only on iodine but also on other vital micronutrients, particularly selenium (Se). This narrative review aims to comprehensively examine the role of selenium in maintaining thyroid health from fetal life through adolescence. Selenium is a key micronutrient involved in thyroid development, hormone synthesis, antioxidant defense, and immune regulation, especially during pregnancy and childhood. Inadequate selenium levels may contribute to the onset, progression, and clinical management of various thyroid disorders, particularly hypothyroidism and autoimmune thyroid diseases. Although scientific evidence supports selenium’s critical functions in hormone metabolism and antioxidant protection, public awareness and monitoring of selenium intake remain insufficient. Beyond the need for further research, there is an urgent call for integrated public health strategies, ranging from sustainable, food-based approaches to targeted clinical screening and educational programs. Promoting awareness of selenium’s importance and incorporating selenium status into maternal and pediatric care protocols could play a significant role in preventing deficiencies and supporting long-term endocrine and neurodevelopmental health. Full article
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11 pages, 274 KB  
Article
Unveiling the Link Between Vitamin D, Hashimoto’s Thyroiditis, and Thyroid Functions: A Retrospective Study
by Rahime Evra Karakaya, Abbas Ali Tam, Pervin Demir, Gülsüm Karaahmetli, Sevgül Fakı, Oya Topaloğlu and Reyhan Ersoy
Nutrients 2025, 17(9), 1474; https://doi.org/10.3390/nu17091474 - 27 Apr 2025
Cited by 1 | Viewed by 3478
Abstract
Background/Objectives: Hashimoto’s thyroiditis (HT) is an autoimmune disease influenced by genetic factors and environmental triggers that affect immune system function. Data suggest that vitamin D may also play a role in the etiopathogenesis of HT. Methods: This retrospective study included patients admitted to [...] Read more.
Background/Objectives: Hashimoto’s thyroiditis (HT) is an autoimmune disease influenced by genetic factors and environmental triggers that affect immune system function. Data suggest that vitamin D may also play a role in the etiopathogenesis of HT. Methods: This retrospective study included patients admitted to the Endocrinology and Metabolic Diseases Outpatient Clinic. Data from individuals aged 18 years and older were analyzed, including serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG), and vitamin D. HT was diagnosed based on the presence of anti-TPO and/or anti-TG antibodies, while individuals with negative results for both were classified as non-HT. Thyroid function was categorized as euthyroid if TSH levels were between 0.55 mU/L and 4.78 mU/L and fT4 levels were between 0.89 ng/dL and 1.76 ng/dL; hypothyroid status was defined as TSH > 4.78 mU/L. Vitamin D levels were classified as deficient (<50 nmol/L), insufficient (50–74.9 nmol/L), or sufficient (≥75 nmol/L). Results: Of the total participants, 25,018 did not have HT, while 27,800 were diagnosed with HT. Vitamin D level was significantly higher in the HT group than the non-HT group (41.43 nmol/L and 39.44 nmol/L, p < 0.001). Vitamin D deficiency was present in 65.5% of the non-HT group and 62.1% of the HT group (p < 0.001). Subgroup analyses based on thyroid function showed that vitamin D levels were highest in the euthyroid HT group and similar in the euthyroid non-HT, hypothyroid non-HT, and hypothyroid HT groups (p < 0.001). Conclusions: In conclusion, while vitamin D levels were higher in the HT group compared to the non-HT group, no clinically significant association between vitamin D levels and HT or autoantibody positivity was observed. Vitamin D deficiency was more prevalent in the hypothyroid group compared to the euthyroid group. This study suggests that although vitamin D deficiency may not be directly involved in the pathogenesis of HT, it may still play a role in modulating immune activity or influencing the disease phenotype.. Full article
(This article belongs to the Section Micronutrients and Human Health)
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18 pages, 2146 KB  
Article
Maternal Metal Ion Status Along Pregnancy and Perinatal Outcomes in a Group of Mexican Women
by Johana Vásquez-Procopio, Johnatan Torres-Torres, Elodia Rojas-Lima, Salvador Espino-y-Sosa, Juan Mario Solis-Paredes, Maribel Sánchez-Martínez, Mari-Cruz Tolentino-Dolores, Otilia Perichart-Perera, Fanis Missirlis and Guadalupe Estrada-Gutierrez
Int. J. Mol. Sci. 2024, 25(23), 13206; https://doi.org/10.3390/ijms252313206 - 8 Dec 2024
Cited by 1 | Viewed by 3167
Abstract
Pregnancy increases the demand for essential metal ions to support fetal development, making the maternal metal ion status a critical determinant of perinatal outcomes. This prospective cohort study examined changes in metal ion levels across the three trimesters, evaluated the influence of preexisting [...] Read more.
Pregnancy increases the demand for essential metal ions to support fetal development, making the maternal metal ion status a critical determinant of perinatal outcomes. This prospective cohort study examined changes in metal ion levels across the three trimesters, evaluated the influence of preexisting metabolic conditions on the metal ion status, and assessed the associations between maternal metal ion levels and perinatal outcomes in 206 pregnant women from the Biochemical and Epigenetic Origin of Overweight and Obesity (OBESO) cohort receiving care at the Instituto Nacional de Perinatología in Mexico City from 2017 to 2020. Six essential metal ions (iron, zinc, copper, calcium, magnesium, and phosphorus) were measured in blood samples using inductively coupled plasma optic emission spectrometry. Significant variations in the metal ion levels were observed across the trimesters, with notable decreases in iron and magnesium and increases in copper as pregnancies progressed. Maternal hypothyroidism was associated with significantly low levels of zinc and magnesium during pregnancy. Regression analyses revealed robust associations between maternal metal ion levels and perinatal outcomes. For instance, declining magnesium levels as pregnancies progressed were positively associated with gestational diabetes (OR: 2.92, p = 0.04; OR: 2.72, p = 0.03). The maternal metal ion status significantly influences perinatal outcomes. Full article
(This article belongs to the Special Issue The Role of Trace Elements in Nutrition and Health)
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11 pages, 412 KB  
Article
Newborn Screening for Six Primary Conditions in a Clinical Setting in Morocco
by Sara El Janahi, Mounir Filali, Zakia Boudar, Amina Akhattab, Rachid El Jaoudi, Najib Al Idrissi, Nouzha Dini, Chakib Nejjari, Raquel Yahyaoui, Michele A. Lloyd-Puryear and Hassan Ghazal
Int. J. Neonatal Screen. 2024, 10(4), 80; https://doi.org/10.3390/ijns10040080 - 4 Dec 2024
Cited by 2 | Viewed by 3932
Abstract
Newborn screening (NBS) represents an important public health measure for the early detection of specified disorders; such screening can prevent disability and death, not only from metabolic disorders but also from endocrine, hematologic, immune, and cardiac disorders. Screening for critical congenital conditions affecting [...] Read more.
Newborn screening (NBS) represents an important public health measure for the early detection of specified disorders; such screening can prevent disability and death, not only from metabolic disorders but also from endocrine, hematologic, immune, and cardiac disorders. Screening for critical congenital conditions affecting newborns’ health is a great challenge, especially in developing countries such as Morocco, where NBS program infrastructure is lacking. In addition, the consanguinity rate is high in Morocco. This study aimed to demonstrate the feasibility of integrating NBS into a diagnostic laboratory for routine analysis. Six primary severe conditions were included: congenital hypothyroidism (CH), cystic fibrosis (CF), phenylketonuria (PKU), glucose-6-phosphate dehydrogenase deficiency (G6PD), congenital adrenal hyperplasia (CAH), and hemoglobinopathies. Methods: A retrospective investigation was carried out to examine the outcomes of NBS in Casablanca, Morocco. A total of 5511 newborn blood samples were collected via heel-prick sampling and tested for the above disorders. Most of the samples were collected within the third and sixth days of birth. The dried blood spots were analyzed via a quantitative immunofluorescence technique and isoelectric focusing. Results: A total of 72 newborns had one of the six pathological conditions. The most prevalent disorders were hemoglobinopathies, which were identified in 47 newborns (0.9%), with 29 having HbC carrier status (0.5%), 15 having Hb S carrier status (0.3%), and 3 having an Hb Bart’s carrier profile (0.05%). This was followed by G6PD deficiency, which was found to affect 16 newborns (0.32% of cases). CF was found in one case (0.02%), whereas five newborns (0.09%) tested positive for CAH. Additionally, two newborns (0.04%) tested positive for CH, and one newborn tested positive for PKU (0.02%). Conclusion: Our findings underscore the importance and success of NBS programs in preventing morbidity and mortality and improving the quality of life of affected neonates. The significant gap in data and research on these disorders within the Moroccan population highlights the urgent need to integrate NBS into routine practice in diagnostic laboratories across Morocco. This integration is crucial for enhancing the health and well-being of Moroccan newborns. Full article
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18 pages, 1326 KB  
Article
The Impact of Gestational Diabetes Mellitus on Minipuberty in Girls
by Karolina Kowalcze, Sofia Burgio, Giuseppe Gullo, Joanna Kula-Gradzik, Johannes Ott and Robert Krysiak
Int. J. Mol. Sci. 2024, 25(21), 11766; https://doi.org/10.3390/ijms252111766 - 1 Nov 2024
Cited by 2 | Viewed by 1526
Abstract
Minipuberty is the second phase of physiological activation of the reproductive axis, playing a role in the postnatal development of sexual organs. The course of female minipuberty was found to be affected by low maternal vitamin D status and hypothyroidism during pregnancy. The [...] Read more.
Minipuberty is the second phase of physiological activation of the reproductive axis, playing a role in the postnatal development of sexual organs. The course of female minipuberty was found to be affected by low maternal vitamin D status and hypothyroidism during pregnancy. The aim of the current study was to assess the hormonal profile and the size of sexual organs in daughters of mothers with gestational diabetes mellitus. The study included three matched groups of infant girls: daughters of healthy women without metabolic disorders during pregnancy (group 1), daughters of women with poorly controlled gestational diabetes mellitus (group 2), and daughters of women with gestational diabetes mellitus adequately controlled during pregnancy (group 3). Urinary levels of gonadotropins, salivary levels of estradiol, testosterone, DHEA-S and progesterone, ovarian volume, uterine length and breast diameter were measured from postnatal month 1 to postnatal month 18. Concentrations of FSH, LH and estradiol were higher, while concentration of progesterone was lower in group 2 than in the remaining groups. There were no between-group differences in concentrations of testosterone and DHEA-S. Levels of LH, FSH, estradiol and progesterone correlated with maternal whole-blood levels of glycated hemoglobin. Group 2 was also characterized by the longest detection periods for LH and estradiol. Ovarian volume, uterine length and breast diameter were greater in group 1 than in the remaining two groups. Over the entire observation period, there were no differences in hormone levels and sizes of the sexual organs between groups 1 and 3. The obtained results suggest that poorly controlled, but not well controlled, gestational diabetes mellitus affects the course of female minipuberty. Full article
(This article belongs to the Special Issue Pathogenesis of Pregnancy-Related Complication (5th Edition))
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13 pages, 3925 KB  
Brief Report
Kisspeptin-10 Improves Testicular Redox Status but Does Not Alter the Unfolded Protein Response (UPR) That Is Downregulated by Hypothyroidism in a Rat Model
by Luciano Cardoso Santos, Jeane Martinha dos Anjos Cordeiro, Maria Clara da Silva Galrão Cunha, Bianca Reis Santos, Luciana Santos de Oliveira, Adriana Lopes da Silva, Erikles Macêdo Barbosa, Raquel Vieira Niella, Gustavo José Cota de Freitas, Daniel de Assis Santos, Rogéria Serakides, Natália de Melo Ocarino, Stephanie Carvalho Borges, Mário Sérgio Lima de Lavor and Juneo Freitas Silva
Int. J. Mol. Sci. 2024, 25(3), 1514; https://doi.org/10.3390/ijms25031514 - 26 Jan 2024
Cited by 2 | Viewed by 3508
Abstract
Hypothyroidism compromises the testicular redox status and is associated with reduced sperm quality and infertility in men. In this regard, studies have demonstrated the antioxidant potential of kisspeptin in reproductive and metabolic diseases. In this study, we evaluate the effects of kisspeptin-10 (Kp10) [...] Read more.
Hypothyroidism compromises the testicular redox status and is associated with reduced sperm quality and infertility in men. In this regard, studies have demonstrated the antioxidant potential of kisspeptin in reproductive and metabolic diseases. In this study, we evaluate the effects of kisspeptin-10 (Kp10) on the testicular redox, as well as mediators of the unfolded protein response (UPR) in adult rats with hypothyroidism. Adult male Wistar rats were randomly separated into the Control (n = 15), Hypo (n = 13) and Hypo + Kp10 (n = 14) groups, and hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals received Kp10. Testis samples were collected for enzymatic, immunohistochemical and/or gene evaluation of mediators of oxidative stress (TBARs, lipid hydroperoxides (LOOH), ROS, peroxynitrite, SOD, CAT and GPX), endoplasmic reticulum stress (GRP78, ATF6, PERK, CHOP, HO-1 and sXBP1) and antiapoptocytes (BCL-2). Hypothyroidism increased apoptosis index, TBARS and LOOH concentrations, and reduced testicular gene expression of Sod1, Sod2 and Gpx1, as well as the expression of Grp78, Atf6, Ho1 and Chop. Treatment with Kp10, in turn, reduced testicular apoptosis and the production of peroxynitrite, while increased SOD1 and GPX ½ expression, and enzymatic activity of CAT, but did not affect the lower expression of UPR mediators caused by hypothyroidism. This study demonstrated that hypothyroidism causes oxidative stress and dysregulated the UPR pathway in rat testes and that, although Kp10 does not influence the low expression of UPR mediators, it improves the testicular redox status, configuring it as an important antioxidant factor in situations of thyroid dysfunction. Full article
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21 pages, 1595 KB  
Article
The Influence of Hypothyroid Metabolic Status on Blood Coagulation and the Acquired von Willebrand Syndrome
by Manuela Andrea Hoffmann, Sarah N. Knoll, Pia-Elisabeth Baqué, Florian Rosar, Inge Scharrer, Stefan Reuss and Mathias Schreckenberger
J. Clin. Med. 2023, 12(18), 5905; https://doi.org/10.3390/jcm12185905 - 11 Sep 2023
Cited by 2 | Viewed by 2721
Abstract
The intent of this prospective study aimed to identify the influence of hypothyroid metabolic status on the coagulation and fibrinolytic system and association with the acquired von Willebrand syndrome (VWS-ac). We compared 54 patients without substitution therapy after radical thyroidectomy with 58 control [...] Read more.
The intent of this prospective study aimed to identify the influence of hypothyroid metabolic status on the coagulation and fibrinolytic system and association with the acquired von Willebrand syndrome (VWS-ac). We compared 54 patients without substitution therapy after radical thyroidectomy with 58 control subjects without pathological thyroid-stimulating-hormone (TSH)-values. Patients with TSH > 17.5 mU/L over a period of >4 weeks were included. The control-collective was selected based on age and sex to match the patient-collective. The data were collected using laboratory coagulation tests and patient questionnaires; a bleeding score was determined. There were significant differences in the measurement of activated-partial-thromboplastin-time (aPTT/p = 0.009), coagulation-factor VIII (p < 0.001) and von-Willebrand-activity (VWF-ac/p = 0.004) between the patient and control groups. The patient cohort showed an increased aPTT and decreased factor VIII and VWF-ac. 29.7% of the patient-collective compared to 17.2% of the control subjects met the definition of VWS-Ac (p = 0.12). The bleeding score showed significantly more bleeding symptoms in patients with a laboratory constellation of VWS-ac (no family history; p = 0.04). Our results suggest hypocoagulability in hypothyroid patients. Hypothyroidism appears to have a higher incidence of VWS-ac. The increased risk of bleeding complications in hypothyroid patients may be of relevant importance for the outcome, especially in the context of invasive interventions. Full article
(This article belongs to the Section Epidemiology & Public Health)
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17 pages, 827 KB  
Article
Interactions between Polygenetic Variants and Lifestyle Factors in Hypothyroidism: A Hospital-Based Cohort Study
by Da Sol Kim and Sunmin Park
Nutrients 2023, 15(17), 3850; https://doi.org/10.3390/nu15173850 - 3 Sep 2023
Cited by 9 | Viewed by 3836
Abstract
Hypothyroidism is a prevalent endocrine disorder and is associated with a variety of metabolic disturbances. This study aimed to investigate the polygenic variants associated with hypothyroidism risk and the interaction of polygenic risk scores (PRS) with dietary patterns in influencing disease risk in [...] Read more.
Hypothyroidism is a prevalent endocrine disorder and is associated with a variety of metabolic disturbances. This study aimed to investigate the polygenic variants associated with hypothyroidism risk and the interaction of polygenic risk scores (PRS) with dietary patterns in influencing disease risk in 56,664 participants aged >40 in a hospital-based cohort. The participants were classified as having hypothyroidism (n = 870) diagnosed by a physician and no hypothyroidism (n = 55,794). Genetic variants associated with hypothyroidism were identified using a genome-wide association study (GWAS). Genetic variants interacting with each other were selected using a generalized multifactor dimensionality reduction analysis, and the PRS generated was evaluated for interaction with lifestyle parameters. Coffee, alcohol, meat intake, and a Korean balanced diet were inversely associated with hypothyroidism risk, as were selenium, copper, and manganese intakes. White blood cell (WBC) counts and serum alkaline phosphatase and triglyceride concentrations were positively associated with hypothyroidism risk, as were osteoporosis and thyroid cancer. The GMDR analysis generated a three-single nucleotide polymorphism (SNP) model comprising dual oxidase-1 (DUOX1)_rs1648314; thyroid-stimulating hormone receptor (TSHR)_rs75664963; and major histocompatibility complex, class-II, DQ Alpha-1 (HLA-DQA1)_rs17426593. The PRS derived from the three- and seven-SNP models were associated with a 2.11- and 2.32-fold increase in hypothyroidism risk, respectively. Furthermore, the PRS from the three-SNP model showed interactions with WBC counts, wherein the positive association with hypothyroidism risk was more pronounced in participants with low WBC counts than those with high WBC counts (≥4 × 109 /L). Dietary patterns, such as the plant-based diet (PBD) and the Western-style diet (WSD), along with smoking status, exhibited interactions with the PRS, influencing hypothyroidism risk. In participants with a high PRS, those in the high-PBD, low-WSD, and smoker groups had a higher proportion of hypothyroidism than those in the low-PBD, high-WSD, and non-smoker groups. In conclusion, genetic variants related to immunity and thyroid hormone secretion were linked to hypothyroidism risk, and their PRS interacted with PBD and WSD intake and smoking status. These results contribute to a better understanding of hypothyroidism and its prevention strategies for precision medicine intervention. Full article
(This article belongs to the Special Issue Nutrition and Gene Interaction)
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12 pages, 305 KB  
Article
Retinol and Pro-Vitamin A Carotenoid Nutritional Status during Pregnancy Is Associated with Newborn Hearing Screen Results
by Rebecca Slotkowski, Matthew Van Ormer, Anum Akbar, Olivia Paetz, Taija Hahka, Maranda Thompson, Alyssa Freeman, Alexandra Hergenrader, Sarah Sweeney, Zeljka Korade, Thiago Genaro-Mattos, Corrine Hanson, Ann Anderson-Berry and Melissa Thoene
Nutrients 2023, 15(4), 800; https://doi.org/10.3390/nu15040800 - 4 Feb 2023
Cited by 5 | Viewed by 3120
Abstract
The prenatal period is critical for auditory development; thus, prenatal influences on auditory development may significantly impact long-term hearing ability. While previous studies identified a protective effect of carotenoids on adult hearing, the impact of these nutrients on hearing outcomes in neonates is [...] Read more.
The prenatal period is critical for auditory development; thus, prenatal influences on auditory development may significantly impact long-term hearing ability. While previous studies identified a protective effect of carotenoids on adult hearing, the impact of these nutrients on hearing outcomes in neonates is not well understood. The purpose of this study is to investigate the relationship between maternal and umbilical cord plasma retinol and carotenoid concentrations and abnormal newborn hearing screen (NHS) results. Mother–infant dyads (n = 546) were enrolled at delivery. Plasma samples were analyzed using HPLC and LC–MS/MS. NHS results were obtained from medical records. Statistical analysis utilized Mann–Whitney U tests and logistic regression models, with p ≤ 0.05 considered statistically significant. Abnormal NHS results were observed in 8.5% of infants. Higher median cord retinol (187.4 vs. 162.2 μg/L, p = 0.01), maternal trans-β-carotene (206.1 vs. 149.4 μg/L, p = 0.02), maternal cis-β-carotene (15.9 vs. 11.2 μg/L, p = 0.02), and cord trans-β-carotene (15.5 vs. 8.0 μg/L, p = 0.04) were associated with abnormal NHS. Significant associations between natural log-transformed retinol and β-carotene concentrations and abnormal NHS results remained after adjustment for smoking status, maternal age, and corrected gestational age. Further studies should investigate if congenital metabolic deficiencies, pesticide contamination of carotenoid-rich foods, maternal hypothyroidism, or other variables mediate this relationship. Full article
(This article belongs to the Section Micronutrients and Human Health)
20 pages, 2118 KB  
Review
3,5-T2-an Endogenous Thyroid Hormone Metabolite as Promising Lead Substance in Anti-Steatotic Drug Development?
by Rajas Sane, Eva K. Wirth and Josef Köhrle
Metabolites 2022, 12(7), 582; https://doi.org/10.3390/metabo12070582 - 23 Jun 2022
Cited by 9 | Viewed by 4277
Abstract
Thyroid hormones, their metabolites, and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid beta-oxidation, cholesterol metabolism, [...] Read more.
Thyroid hormones, their metabolites, and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid beta-oxidation, cholesterol metabolism, and metabolic pathways of glucose homeostasis. Many of these effects are mediated by T3 receptor β1-dependent modulation of transcription. However, rapid non-canonical mitochondrial effects have also been reported, especially for the metabolite 3,5-diiodothyronine (3,5-T2), which does not elicit the full spectrum of “thyromimetic” actions inherent to T3. Most preclinical studies in rodent models of obesity and first human clinical trials are promising with respect to the antisteatotic hepatic effects, but potent agents exhibit unwanted thyromimetic effects on the heart and/or suppress feedback regulation of the hypothalamus-pituitary-thyroid-periphery axis and the fine-tuned thyroid hormone system. This narrative review focuses on 3,5-T2 effects on hepatic lipid and glucose metabolism and (non-)canonical mechanisms of action including its mitochondrial targets. Various high fat diet animal models with distinct thyroid hormone status indicate species- and dose-dependent efficiency of 3,5-T2 and its synthetic analogue TRC150094. No convincing evidence has been presented for their clinical use in the prevention or treatment of obesity and related metabolic conditions. Full article
(This article belongs to the Special Issue Metabolic Effects of the Intracellular Regulation of Thyroid Hormone)
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