Search Results (33)

Background: Hemangiomatosis is a rare condition characterized by the presence of multiple benign vascular tumors that may affect various organs, including the skin, liver, and spleen. Complications are closely linked to the location and size of the lesions. Case Presentation: We describe a rare presentation of infantile hemangiomatosis with widespread cutaneous and oral mucosal lesions, further complicated by splenic and hepatic involvement and secondary cholestasis. The initial progression was unfavorable, with an increase in both the number and size of the lesions. Cardiologic evaluation identified minor valvular insufficiencies, but no secondary cardiac failure. Treatment with propranolol and prednisone was initiated, with a slow favorable evolution. There were no new hemangiomas developed, and those on the face and limbs decreased in size, some disappearing entirely. Hepatic and splenic hemangiomas regressed more slowly, but their reduction and the improvement of cholestasis were progressive. Due to significant iatrogenic Cushing’s syndrome, prednisone was gradually tapered. Transient subclinical hypothyroidism occurred during treatment, resolving spontaneously. Conclusions: The present case illustrates the rarity and complexity of multifocal infantile haemangiomatosis and highlights the importance of early diagnosis, comprehensive organ evaluation, and tailored multidisciplinary management. It clearly demonstrates that prompt intervention and careful therapy adjustment can lead to favorable outcomes even in the setting of extensive visceral involvement. Full article

Background/Objectives: Neonatal screening programmes for thyroid function testing, based on thyroid-stimulating hormone (TSH) assessment, detect both Permanent Congenital Hypothyroidism (PCH) and Transient Congenital Hypothyroidism (TCH). Maternal iodine-deficient dietary intake may result in compensatory neonatal TSH elevation; screening for Congenital Hypothyroidism (CH) is used as an indicator of the degree of iodine deficiency and of its control. In Greece, newborn screening for CH, using TSH measurement in dried blood spots (Guthrie card), began in 1979 through the Institute of Child Health (ICH). Although the general Greek population is considered iodine-replete, most pregnant Greek people are mildly iodine deficient according to the stricter WHO criteria. The aim of this retrospective study was to record the cases of TCH and the main causative factors over a 10-year period (2010–2019) in Greece, when the country was deemed to be iodine-replete. Methods: The number of births in Greece between 2010 and 2019 was retrieved from the Hellenic Statistical Authority (ELSTAT) archives: 952,109 births were recorded. The total number of newborns assessed through the ICH was 951,342 (99%). During this period, 22,391 newborns were identified to have TSH > 7 mIU/L after the second check on the initial card. Among those, 17,992 underwent retesting with a serum sample. Out of the retested newborns, 1979 were screened positive for CH and immediately began treatment with levothyroxine. We followed up with families, paediatricians, and paediatric endocrinologists to determine whether L-thyroxine therapy had been successfully discontinued for at least two months after the child’s third birthday. Successful contact was achieved with 889 individuals. From this group, 329 children had successfully discontinued thyroxine, classified as TCH. Demographic data, including gender, gestational age, and birth weight, were collected from the archives of the ICH. Maternal data, including thyroid medication use and the presence of elevated thyroid autoantibodies during pregnancy and childbirth, were also recorded. Results: Logistic regression analysis revealed that, while controlling for all other predictor variables, the odds ratio of transient hypothyroidism was 2.078 (95% CI: 1.530 to 2.821) for prematurely born children compared to those born at term. The effects of other factors on TCH versus PCH were not significant. Conclusions: It seems that prematurity is the main factor contributing to Transient Congenital Hypothyroidism in Greece, a recently iodine-replete country. Full article

The absence of biochemical newborn screening (NBS) delays the diagnosis and treatment of congenital hypothyroidism (CH), resulting in irreversible neurodevelopmental damage. To determine the age at diagnosis for CH among Algerian children and to describe its clinical and biological characteristics, etiology, and outcome, we conducted a multicenter retrospective cohort study involving 288 children with CH across 20 pediatric centers between 2005 and 2023. The median age at diagnosis was 1.6 months, and only 28% of patients started treatment before 30 days. Prolonged neonatal jaundice was the most frequently presented symptom (58%), severe CH (fT₄ < 5 pmol/L) was observed in 35% and 52% received an insufficient initial dose of L-T₄. The median IQ of the 47 patients tested was 86; 11% had an IQ < 70, and a negative correlation was found between age at diagnosis and IQ (r = −0.48, p = 0.001). In children reassessed at age 3, 51% had normal thyroid function, indicating transient CH. Delayed diagnosis and suboptimal treatment of CH remain major challenges in Algeria, leading to substantial neurodevelopmental deficits. Pediatricians must remain cognizant of early clinical signs of CH to allow for timely diagnosis and intervention. Biochemical NBS for CH in Algeria is needed. Full article

Introduction: Takotsubo cardiomyopathy (TCM), also known as stress cardiomyopathy or Broken Heart Syndrome, is a reversible, transient state of myocardial dyskinesis and apical ballooning. Infrequently, TCM may progress to severe life-threatening complications such as cardiogenic shock. Early mechanical circulatory support (MCS) is crucial to myocardial recovery in these cases. We present one of the first cases of TCM successfully treated with the advanced micro-axial minimally invasive Impella 5.5 with SmartAssist MCS device. Case Presentation: A female in her late 70s with a history of hypothyroidism, atrial fibrillation post-ablation, and cholelithiasis was referred to our facility for an elective cholecystectomy. Post-anesthesia induction with propofol 2.1 mg/kg (140 mg bolus), she became bradycardic and hypotensive, eventually leading to asystole, requiring CPR and termination of the procedure. Echocardiography revealed a left ventricular ejection fraction (LVEF) of 24% with mid-ventricular akinesis and apical ballooning with mild mitral regurgitation, suggesting the diagnosis of TCM. Cardiac catheterization showed RA 20 and mean PA 42 mmHg. Lactate was 18.7 mmol/L and LDH 1776 U/L, suggesting progressive shock. Continuous epinephrine 0.1 mcg/kg/min and norepinephrine 0.06 mcg/kg/min were titrated for BP 97/58, and she was initially supported with the Impella CP device. Despite aggressive efforts, rising LDH levels and increased vasopressor needs indicated inadequate organ perfusion, requiring an upgrade to Impella 5.5. Impella 5.5 support for 11 days led to impressive myocardial recovery, leading to reductions, and eventual discontinuation, of inotropes and vasopressors. Post-Impella 5.5 explantation, her LVEF was 59–65% and she was discharged with Mobile Cardiac Outpatient Telemetry (MCOT) monitoring for her arrhythmias and reinitiation of guideline-directed medical therapies (GDMTs) for her comorbidities. Her 2-month follow-up shows sustained LVEF greater than 45% with functional improvements. Conclusions: Early escalation within 24 h of Impella CP to Impella 5.5 provided stabilization of cardiometabolic shock, preventing end-organ damage, allowing recovery of native heart function while maintaining ambulatory status, and allowing for optimizing medical therapy. It presents a safe, minimally invasive, and cost-effective intervention in TCM cases refractory to GDMT or when additional time is needed for decision-making in cases presenting with CS. Full article

Congenital hypothyroidism (CH) is one of the major preventable causes of intellectual disability. This study evaluates the incidence of CH through a newborn screening (NBS) program in eastern Morocco. A descriptive cross-sectional design was used and heel prick blood samples were collected on blotting paper to measure Thyroid-Stimulating Hormone (TSH) using an immunofluorimetric assay. 4062 newborns were screened (51.3% male, 48.7% female). TSH levels significantly varied by age: newborns sampled before 24 h had a higher median TSH (3.7 µU/mL [0.10–28.90]) compared to those sampled at 24 h or more (2.1 µU/mL [0.10–32.30]; p < 0.001). Using age-specific cut-off values, 18 suspected CH cases were recalled (recall rate: 0.44%). Among the 16 cases who completed confirmatory testing, 4 had transient hyperthyrotropinemia (HTT), characterized by mildly abnormal serum TSH and T4 levels that normalized spontaneously after few months without treatment. Three cases were diagnosed with CH confirmed at birth with markedly elevated serum TSH concentrations and significantly reduced T4 levels. Consequently, the birth prevalence of CH confirmed at birth was 1:1354 live births. The median preanalytical delay was 6 days (IQR: 3–12) and the TSH result turnaround was 8 days (IQR: 5–15), potentially affecting timely intervention. This first report from eastern Morocco confirms the relevance of neonatal screening but highlights delays that must be addressed to enhance early diagnosis and management. Full article

Radioactive iodine (RAI) therapy plays a fundamental role in the management of differentiated thyroid cancer (DTC) following appropriate surgical intervention. High levels of TSH are required in order to achieve maximum RAI uptake in residual thyroid tissue or metastatic cells. The two techniques that are most commonly used are thyroid hormone withdrawal (THW), which induces endogenous TSH elevation by creating a hypothyroid state, and exogenous stimulation with recombinant human TSH (rhTSH). This review compares both approaches over a range of DTC risk categories. Extensive evidence demonstrates that rhTSH and THW yield equivalent oncological outcomes, including remnant ablation success, recurrence-free survival, and overall survival, in low-, intermediate-, and high-risk disease. Additionally, rhTSH maintains quality of life by avoiding hypothyroid symptoms. While THW continues to be an excellent option when there is a lack of availability of rhTSH, its disadvantages, particularly the transient hypothyroid state, must be carefully weighed against the demonstrated equivalence in efficacy. In current clinical practice, rhTSH is frequently the preferred option for its convenience, safety, and patient-centered benefits; however, the selection of the optimal approach should be based on individual clinical circumstances and patients’ preferences, as well as resource considerations. Full article

Congenital hypothyroidism (CH) is a critical condition in infancy where early detection is vital for optimal development. This study aimed to evaluate the sensitivity of Aotearoa New Zealand’s Newborn Metabolic Screening “Low Birth Weight” protocol for detecting CH in preterm infants. A 10-year audit was conducted on 2935 preterm infants (<2000 g or ≤34 weeks gestation) screened within NICUs or SCBUs in the Auckland region. The study assessed both screen-detected and clinically detected cases of CH. Data were collected from screening and clinical records to evaluate the sensitivity and reliability of the current protocol. The audit identified 19 cases of primary CH, with a 1:154 incidence. Thirteen cases met the criteria for inclusion in the audit. Just over half of the eligible cases (7/13) were screen-detected, while the remaining were detected clinically, suggesting limitations in screening sensitivity. The analysis revealed that the protocol missed permanent as well as transient cases, and that biochemical severity was not predictive of permanence. A revised screening protocol was developed and commenced in July 2024. Full article

Background: Lithium is a cornerstone in the treatment of bipolar disorder (BD). However, lithium use requires careful monitoring of thyroid function due to associated dysfunctions. The aim of our real-world study is to retrospectively evaluate the impact of lithium on thyroid function and how these thyroid alterations can be measured and managed. Methods: A retrospective observational study was performed on 150 patients with BD who started lithium treatment at the University Hospital of Siena. Thyroid function was assessed at baseline and after the introduction of lithium by measuring TSH, T3, and T4 levels at baseline and after 3, 6, 9, and 12 months, during which changes in psychiatric symptoms were also evaluated using specific psychometric scales. Results: Significant increases in TSH levels were observed at 3 and 6 months, while T3 and T4 levels decreased significantly at 3 months. Transient thyroid dysfunction occurred in 36.7% of patients, but normalized without the discontinuation of lithium or need for thyroid replacement therapy in most cases; however, replacement therapy was initiated in 8.7% of patients. There were no significant differences in treatment response between patients with and without thyroid abnormalities, as the abnormalities were transient or resolved. Conclusions: In our sample, lithium induced some cases of hypothyroidism, which, being transient or corrected with replacement therapy, did not interfere with symptomatic improvement. These findings underscore the necessity for continuous thyroid function monitoring during lithium therapy. Clinicians should be prepared to initiate thyroid replacement therapy, when necessary, as timely management can prevent the interruption of lithium treatment and ensure ongoing symptomatic improvement in BD patients. Future studies could include larger and more diverse populations to validate these findings further, extending the follow-up period beyond 12 months to better observe long-term thyroid function trends and management outcomes. Full article

Some preterm and sick neonates have altered biochemical profiles and follow-up newborn screening (NBS) collections are recommended. The Victorian NBS program historically recommended repeat collections for babies with birth weight < 1500 g (managed by the maternity service provider) and 3 weeks post-transfusion (managed by the laboratory). We aimed to determine adherence to current guidelines and review the guidelines to improve NBS performance. To do this, we audited data from 348,584 babies between January 2018 and June 2022. Babies with a recorded birth weight of <1500 g were filtered for inclusion. For the overall review and visualization of the protocol, we sourced information from the literature, our professional society and tertiary hospital services. A total of 2647 babies had a birth weight recorded between 200 and 1499 g. Of these, 2036 (77%) had a second sample collected, indicating that >1 in 5 babies were not receiving a follow-up collection. Our timing of repeat collections for transfused babies, requiring a 3-week follow-up collection, was longer than in other Australasian jurisdictions. A new combined “sick–prem protocol” was launched to support repeat collections and after a 1-year review achieved 95% compliance. We recommend NBS laboratories audit preterm and sick neonate repeat collections to ensure appropriate follow-up. This should be supported with a visual process map to aid education and compliance. Full article

Thyroid dyshormonogenesis (THD) is a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones. Genetic variants in DUOX2 can cause partial to total iodination organification defects and clinical heterogeneity, from transient to permanent congenital hypothyroidism. The aim of this study was to undertake a molecular characterization and genotype–phenotype correlation in patients with THD and candidate variants in DUOX2. A total of 31 (19.38%) patients from the Catalan Neonatal Screening Program presented with variants in DUOX2 that could explain their phenotype. Fifteen (48.39%) patients were compound heterozygous, 10 (32.26%) heterozygous, and 4 (12.90%) homozygous. In addition, 8 (26.67%) of these patients presented variants in other genes. A total of 35 variants were described, 10 (28.57%) of these variants have not been previously reported in literature. The most frequent variant in our cohort was c.2895_2898del/p.(Phe966SerfsTer29), classified as pathogenic according to reported functional studies. The final diagnosis of this cohort was permanent THD in 21 patients and transient THD in 10, according to reevaluation and/or need for treatment with levothyroxine. A clear genotype–phenotype correlation could not be identified; therefore, functional studies are necessary to confirm the pathogenicity of the variants. Full article

Minipuberty is a term describing transient postnatal activation of the hypothalamic–pituitary–gonadal axis, likely playing an important role in the postnatal growth of female genital organs and breasts. Unlike infant boys, there are no data concerning the impact of gestational hypothyroidism on the course of minipuberty in infant girls. Therefore, the aim of the current study was to investigate the reproductive axis and genital organs in daughters of women with thyroid hypofunction during pregnancy. The study population included three matched groups of infant girls: offspring of women with thyroid hypofunction non-substituted or inadequately treated during gestation (group 1), descendants of women adequately substituted throughout pregnancy (group 2), and daughters of healthy women (group 3). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone, and androgens (testosterone, androstenedione, and dehydroepiandrosterone sulfate) and urine levels of gonadotropins were measured monthly from month 1 to month 6, once every two months between postnatal months 6 and 12, and once every three months between postnatal months 12 and 18. During each visit, we also determined ovarian volume, uterine length, and breast diameter. Concentrations of FSH, LH, and estradiol were lowest in group 1, and this group was also characterized by the shortest detection period for gonadotropins and estradiol. These differences were paralleled by differences in ovarian volume, uterine length, and breast diameter. There were no differences between groups 2 and 3 in levels of both hormones and in the size of the measured structures. The obtained results seem to indicate that non-substituted or inadequately substituted hypothyroidism during pregnancy may impair the course of minipuberty in the female offspring. Full article

Background and Objectives: Congenital thyroid dyshormonogenesis is caused by alterations in the synthesis of thyroid hormones in a newborn. Additionally, 10 to 20% of these cases are hereditary, caused by defects in proteins involved in hormonal synthesis. One of the most common causes is mutations in the thyroid peroxidase (TPO) enzyme gene, an autosomal recessive disease. We aimed to detect mutations of the TPO gene in 12 Chilean patients with congenital hypothyroidism due to dyshormonogenesis (CHD) and to characterize these patients clinically and molecularly. Materials and Methods: Twelve patients under 20 years of age with CHD, controlled at San Juan de Dios Hospital in Santiago, Chile, were selected according to the inclusion criteria: elevated neonatal TSH, persistent hypothyroidism, and thyroid normotopic by imaging study. Those with deafness, Down syndrome, and central or transient congenital hypothyroidism were excluded. Blood samples were taken for DNA extraction, and the 17 exons and exon–intron junctions of the TPO gene were amplified by PCR. The PCR products were sequenced by Sanger. Results: Two possibly pathogenic mutations of the TPO gene were detected: c.2242G>A (p.Val748Met) and c.1103C>T (p.Pro368Leu). These mutations were detected in 2 of 12 patients (16.6%): 1 was compound heterozygous c.1103C>T/c.2242G>A, and the other was heterozygous for c.2242G>A. In the diagnostic confirmation test, both patients presented diffuse hyper-uptake goiter on thyroid scintigraphy and high TSH in venous blood (>190 uIU/mL). Conclusions: The frequency of patients with possibly pathogenic mutations in TPO with CHD was 16.6%. Its study would allow for genetic counseling to be offered to the families of affected patients. Full article

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) have revolutionized the management of many types of solid tumors, including metastatic renal cell carcinoma (mRCC). Both sequential and combinatorial therapeutic strategies utilizing anti-PD-1 monoclonal antibodies (mAbs) and anti-angiogenic tyrosine kinase inhibitors (TKIs) have demonstrated to improve the survival of patients with mRCC as compared to standard therapies. On the other hand, both ICIs and TKIs are well known to potentially cause thyroid disorder adverse events (TDAEs). However, in the context of sequential therapeutic strategy, it is not clear whether prior anti-angiogenic TKI may increase the risk and/or the severity of ICI-related TDAEs. In this work, by describing and analyzing a case series of mRCC patients treated sequentially with prior TKIs and then with ICIs, we investigated the role of prior anti-angiogenic TKI-based treatment as a potential predisposing factor to anti-PD-1-mediated recurrent TDAEs, as well as its potential impact on the clinical characteristics of nivolumab-mediated recurrent TDAEs. Fifty mRCC patients were included in the analysis. TKI-mediated TDAEs were reported in ten out of fifty patients. TKI-mediated TDAEs were characterized by hypothyroidism in all ten patients. Specifically, 40%, 40% and 20% of patients presented grade 1, 2 and 3 hypothyroidisms, respectively. Following tumor progression and during anti-PD-1 nivolumab treatment, five out of ten patients developed anti-PD-1 nivolumab-mediated recurrent TDAEs. Anti-PD-1 nivolumab-mediated recurrent TDAEs were characterized by an early transient phase of thyrotoxicosis and a late phase of hypothyroidism in all five patients. The TDAEs were grade 1 and 2 in four and one patients, respectively. Prior anti-angiogenic TKI did not modify the clinical characteristics of nivolumab-mediated recurrent TDAEs. However, all five patients required an increased dosage of levothyroxine replacement therapy. In conclusion, our work suggests that prior anti-angiogenic TKI-based treatment significantly increases the risk of ICI-mediated recurrent TDAEs in patients with mRCC without modifying their clinical characteristics. The most relevant effect for these patients is the need to increase the dosage of lifelong levothyroxine replacement therapy. Full article

Congenital hypothyroidism (CH) may have major detrimental effects on growth and neurological development, but early intervention leads to excellent outcomes. CH is classified as transient or permanent, primary or secondary, with primary CH being the most common neonatal endocrine disorder. Most patients with CH do not present any typical signs and symptoms of hypothyroidism shortly after birth, partly due to transplacental maternal thyroid hormone transfer and residual neonatal thyroid function. This paper reports on two CH cases. During the initial Neonatal Intensive Care Unit (NICU) admission phase, CH was not suspected due to nonspecific signs. The distinct characteristics of our cases are as follows: both infants were admitted to the NICU for respiratory distress syndrome, requiring invasive mechanical ventilation, and both were born to diabetic mothers. Following extubation, they both showed similar neurological issues, including reduced muscle tone and feeding difficulties. Initially, those symptoms were attributed to delayed clearance of analgesic and sedative medication. However, symptoms progressively worsened over time. Subsequent tests revealed both meeting CH diagnostic criteria: an unusual ultrasound indicating thyroid agenesis and abnormal hormone levels. Guided by the pediatric endocrinology team, prompt hormonal treatment was started with improvements in neurocognitive function and feeding. Usually, CH screening involves blood samples from healthy newborns at 2–3 days of life. Abnormal results require confirmation, prompting treatment within two weeks. Certain NICU-admitted infants face higher diagnosis delays, as seen in those two cases where CH screening was postponed. Thus, for all neonates with persistent pathologies unresponsive to standard etiological treatment, conducting a comprehensive anamnestic evaluation of the medical history, along with maternal preconceptional and prenatal nutrition, is recommended. Full article

Newborn screening (NBS) for congenital hypothyroidism (CH) was introduced in Switzerland in 1977, which allowed for the preclinical, biochemical diagnosis. The aim of this study was to evaluate the prevalence of transient CH (tCH) in the canton of Zurich. In this analytical cohort study, all newborns born in the canton of Zurich, between the 1st of January 2000 and the 30st of June 2016, with a TSH value above 15 mU/L (whole blood) were included. There were 115 cases out of 247,918 babies born during the study period. However, 23 cases had to be excluded due to missing data. The definite diagnosis was made after a thyroxine withdrawal at 2 years of age. The total prevalence of confirmed CH and the female to male ratio (f/m) were 1:2695 and 2.17:1; for permanent CH (pCH), 1:3443 and 2.8:1; and for tCH, 1:12,396 and 1:1, respectively. The TSH value was significantly higher in pCH compared to tCH, at 130.3 (62.9–171.9) and 36.4 (26.5–53.3) (median and interquartile range), respectively (p < 0.001). The prevalences found for congenital hypothyroidism and its transient form are comparable to previous studies. TSH concentration at birth was predictive for the further course of the disease. Low birth weight correlated with a tCH, whereas low gestational age did not. The dominance of the female sex in congenital hypothyroidism is supported by a gender ratio of 2.17:1. Full article