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It was aimed to investigate the outcomes of babies referred to a tertiary health center in Turkey for evaluation primary congenital hypothyroidism (CH) through newborn screening. The hospital files of 328 newborns who were referred for CH from newborn screening between June 2013 and June 2020 were retrospectively reviewed. The newborns were evaluated with their clinical characteristics at admission, as well as their follow-up data and final diagnoses. Sixteen (4.9 %) newborns were diagnosed with transient neonatal hyperthyrotropinemia after follow-up. Treatment was initiated in 166 (50.6 %) of the cases with a diagnosis of CH. The median age at initiation of treatment was 17 days (5–69). Treatment was initiated in 88.3 % of the cases in the first month of the life. After at least 3 years of follow-up, 30/120 (20.0 %) of the cases were diagnosed with permanent CH and 11/30 (36.7 %) of them were diagnosed with thyroid dysgenesis. All of the cases who used >37.5 µg per day levothyroxine at the age of 1 or 2 years were diagnosed with permanent CH during their follow-up. For the prediction of transient CH, the sensitivity and specificity of levothyroxine doses of ≤25 µg per day at 1 year of age were calculated as 96.2 and 46.2 %, and for 2 years of age, the sensitivity and specificity were calculated as 97.8 and 65.2 %. In this cohort, 10 % of all referrals result in permanent CH. Thyroid imaging with ultrasonography and levothyroxine dose during follow-up can be guiding in predicting permanent CH. [ABSTRACT FROM AUTHOR]

Congenital hypothyroidism (CHT) is a treatable cause of intellectual disability. Late diagnosis and delayed initiation of treatment leads to irreversible neurodevelopmental and intellectual disability. Thus, newborn screening is crucial. However, 71 % of babies are born in an area with no established newborn screening program and Kenya is not an exception. We aimed to determine the incidence of CHT, developmental outcomes of patients in the absence of newborn screening. A retrospective data of subjects who met the inclusion criteria, newborn and infants from 3 days to 2 years whose thyroid function test (TFT) was undertaken during well baby visit or clinical suspicion of CHT were collected. Laboratory reference range for age was used to interpret the result and TSH>10 Uiu/mL after 6 weeks of life is considered abnormal according to ESPE guideline. Developmental outcome of children was collected from patient file documented by primary physician and parental concern. Of 1,426 children met inclusion criteria, 90 had elevated TSH. Out of which 70 repeat TFT showed normal TSH and free T4. The incidence of abnormal TSH across the different age groups was 2.4 , 7.2 and 10.5 % for ages 0–29 days, 1–11 months, and 1–2 years, respectively with p-value of =0.0002. While 20 cases with CHT identified with incidence of 14 per 1,000 children (1.4 %; 95 % CI: 0.9–2.1 %). Out this 12 (60 %) had poor developmental outcomes. Down's syndrome was the common associated condition 9/20 (45 %). All cases were primary CHT. This study shows high incidence of CHT in a small cohort of patients over 5-year period with poor development outcome. [ABSTRACT FROM AUTHOR]

Introduction: The sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Biallelic loss-of-function variants in the NIS-coding SLC5A5 gene cause congenital dyshormonogenic hypothyroidism due to a defect in the accumulation of iodide, which is required for thyroid hormonogenesis. Objective: We aimed to identify, and if so to functionally characterize, novel pathogenic SLC5A5 gene variants in a patient diagnosed with severe congenital dyshormonogenic hypothyroidism characterized by undetectable radioiodide accumulation in a eutopic thyroid gland, as well as in the salivary glands. Methods: The coding region of the SLC5A5 gene was sequenced using whole-exome sequencing. In silico analysis and in vitro functional characterization of missense SLC5A5 gene variants were performed. Results: Proposita's whole-exome sequencing revealed a novel pair of compound heterozygous missense variants in the SLC5A5 gene, c.1,627G>A (p.G543R) and c.1,684T>A (p.L562M). The parents were heterozygous carriers of the variants as determined by Sanger sequencing of the SLC5A5 gene. The p.G543R variant in the homozygous state has previously been associated with congenital hypothyroidism. The novel p.L562M variant was not reported in the Genome Aggregation Consortium dataset. In silico analysis of the pathogenic impact of the p.L562M variant yielded inconclusive results. Functional in vitro studies showed that the p.L562M variant reduces iodide accumulation due to defective expression of the mutant NIS protein at the plasma membrane. Notably, the aliphatic residue Leu at position 562 in the carboxy terminus of the protein, which is highly conserved in NIS orthologues, is required for NIS plasma membrane expression. Conclusions: We report novel compound heterozygous missense SLC5A5 gene variants causing defective iodide accumulation, thus leading to congenital dyshormonogenic hypothyroidism. [ABSTRACT FROM AUTHOR]

Background: Congenital hypothyroidism (CH) is a pathology that affects various organs, including the testicles. The mechanisms by which this condition alters fertility is unknown. This study aimed at determining if experimental CH affects gonocyte differentiation and arrests meiosis; and the possible role of the Sertoli cell (SC) in this condition. Material and Methods: Two groups of rats consisting of Control group and Methimazole (MMI) induced CH rats were formed. The induction of CH was achieved by the administration of MMI starting on day 16 postcoitum and continued until euthanized. Euthanasia was performed at 5, 8, 10, 16 and 64 days of age. Following this, the testicular tissue of each animal was extracted and processed for histopathological and ultrastructural analysis. In addition, the tissue was used for the determination of proteins and their transcriptions, events which are characteristics of gonocyte differentiation. The SC functionality proteins was determined immunohistochemically, while sperm parameters of the cauda epididymis were verified. Results: CH caused a delay in the gonocyte differentiation, and arrested meiosis and spermiogenesis. These events had long-term repercussions on the quality of the seminiferous epithelium. The results show that CH induces alterations in the functional state of SCs that may have led to the deficiency in the synthesis and/or in the release of molecules necessary for gonocyte differentiation; as well as disorders in the process of meiosis that resulted in sperm absence. Conclusion: These results suggest that CH affects gonocyte differentiation and arrests meiosis, possibly through altering the functional status of SCs. [ABSTRACT FROM AUTHOR]

Background: There is biological plausibility to the link between trace element levels and thyroid hormone metabolism. While some studies found higher concentrations of trace elements in the blood of dysfunctional thyroid patients, others found lower levels. Therefore, it became mandatory to formulate an idea about the circulating levels of selected trace elements as selenium (Se) and zinc (Zn) in children with dysfunctional thyroid disorders. Aim: To investigate the association between dysfunctional thyroid disorders and selected trace elements Se and Zn concentrations in children. Methods: This study was a crosssectional study conducted at the pediatrics department and outpatient clinics of pediatric endocrinology unit, Zagazig University Hospital in the period of about 1.5 year. This study included 300 participants who were evaluated regarding thyroid function, 210 of them had proven dysfunctional thyroid disorder while 90 subjects were healthy individuals. Zn, Se, thyroid function and thyroid antibodies were measured in all children. Results: Regarding trace elements, acquired hypothyroidism group and congenital hypothyroidism group showed significant lower mean zinc level when compared to control group. Also acquired hypothyroidism group showed significantly lower mean Selenium level when compared to control group. Conclusion: Selenium and zinc deficiency was found in children who were found to have dysfunctional thyroid disorders. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Abnormal thyroid function tests (TFTs) are found in a wide range of settings in hospitalised infants. This retrospective descriptive study reviewed management decisions and outcomes of these infants, identifying factors influencing clinicians' decision to treat with thyroxine.Data were collected for all infants referred to the on‐call endocrinology service at a tertiary Australian centre for thyroid dysfunction between 1 July 2019 and 30 June 2021. Electronic medical records were reviewed for birth and neonatal factors, TFTs, relevant investigations, treatment and disposition.Of 124 infants referred to the service over a 2‐year period, 43% (52 out of 120) were premature, with a high rate of comorbidities, including jaundice, hypoglycaemia, respiratory distress and cardiac anomalies. About 57% (69 out of 121) of referrals to the service were from neonatal intensive care units. Investigations to evaluate hypothyroidism included nuclear thyroid scans in 40% (46 out of 114) and ultrasound in 37% (41 out of 112). Levothyroxine treatment was initiated in 66% (77 out of 117) of infants, with 63% (73 out of 117) assigned a presumptive diagnosis of transient congenital hypothyroidism. At the end of the study period, 70% (54 out of 77) remained on thyroid replacement.Our study demonstrates the challenge clinicians face when deciding whether to treat premature and medically unwell infants with abnormal TFTs. Further prospective studies are required to determine predictors of permanent CH in this complex population. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: This study aimed to examine the iodine concentration in the food items consumed by mothers participating in neonatal screening programs in both areas of the Vidarbha region. A developing fetus relies on a consistent supply of iodine for proper brain and body development. During pregnancy, only the mother can provide the necessary iodine levels. If the mother is iodine-deficient, the child will also lack this essential nutrient. Severe deficiency in the mother can lead to significant stunting of the child's brain and body, potentially preventing normal walking, talking, or cognitive function. Even if the mother's deficiency is mild, the child can still be adversely affected, even if they appear healthy at first glance. The detrimental effects on brain development may manifest later in life as poor academic performance and difficulties in managing daily tasks. Material and Method: The present cross-sectional research will be performed in collaboration with the Departments of Biochemistry, Obstetrics and Gynecology, Community Medicine, and Pediatrics at Jawaharlal Nehru Medical College Sawangi (Meghe) Wardha, along with Datta Meghe Institute of Medical Science (Deemed University) in Maharashtra, India. Mothers who gave birth agreed to participate by providing written consent for the study. Results: The average iodine concentrations are quite similar across all sources, though hand pumps show slightly more variability. Different staple foods contain varying levels of iodine, with some foods (like pulses) exhibiting a lot of variation, while others (like rice and potatoes) are more consistent in their iodine content. Conclusion: The current study is a hospital-based investigation aimed at screening neonates for congenital hypothyroidism (CH) and does not reflect the broader population. To identify CH, screening of neonates will be conducted within the study area, providing a representative view of the condition. The clinical and pathological effects of CH are subtle and often remain unnoticed. Our findings suggest that the prevalence of iodine reflects dietary quality, educational background, and socioeconomic status, all of which can influence growth and development. There are various factors contributing to CH and inadequate fetal growth beyond low iodine levels, which can disrupt thyroid function. The study indicates that iodine levels are indicative of dietary quality as well as educational and social statuses, potentially impacting growth and development through both dietary deficiencies and other factors. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: This study aimed to evaluate thyroid hormone levels in neonates from the rural and urban Vidarbha region. Over the past decade, neonatal hypothyroidism screening has been conducted using filter paper techniques to identify congenital hypothyroidism (CH). In some screening programs, only T4 is measured initially, with TSH assessed if the T4 levels fall below normal. Conversely, some programs exclusively measure TSH to screen for CH. Currently, initial TSH screening can identify subclinical hypothyroidism in cases where T4 levels are normal, while preliminary T4 testing can reveal congenital hypothyroidism when TSH is elevated. If either T4 or TSH is found to be abnormal during preliminary screening, the other parameter should be monitored. Early diagnosis and prompt treatment are crucial in preventing intellectual disabilities in newborns. Material and Method: The present cross-sectional research will be conducted in collaboration with the Departments of Biochemistry, Obstetrics and Gynecology, Community Medicine, and Pediatrics at Jawaharlal-Nehru Medical College Sawangi (Meghe) Wardha, along with the Datta-Meghe Institute of Medical Science (Deemed University) in Maharashtra, India, and Datta-Meghe Medical College, Shalinitai Meghe Hospital and Research Centre, Nagpur. Results: A total of 272 neonates were tested for Congenital Hypothyroidism (CH) from the study area of the Vidarba region in which 138 neonates were from the rural area and 134 neonates were from the urban area. A total of 144 (53%) males and 128 (47%) females were born in rural and urban areas. In the neonates, it was observed that the Mean ± SD for free T4 and TSH was 0.84 ± 0.15 and 3.83 ± 2.12, respectively. If the free T4 value was less than the lower limit, the TSH value CB ≥25 μIU/ml and plasma ≥10 μIU/ml was considered as screen positive in the present study. Conclusion: Newborn screening programs were established to assess neonates at birth by measuring (TSH) levels. In many screening programs, TSH is the primary marker for evaluating thyroid function and is the preferred test for clinicians diagnosing various thyroid disorders. However, TSH levels can vary significantly and exhibit a broad reference range within the general population, which presents challenges in interpreting the results during newborn screening and in using it later as a clinical diagnostic tool for thyroid function. [ABSTRACT FROM AUTHOR]

PURPOSE: Thyroid peroxidase (TPO) is essential for the synthesis of thyroid hormones. However, specific mutations render TPO antigenic and prone to autoimmune attacks leading to thyroid cancer, TPO deficiency, and congenital hypothyroidism (CH). Despite technological advancement, most experimental procedures cannot quickly identify the genetic causes of CH nor detect thyroid cancer in the early stages. METHODS: We performed saturated computational mutagenesis to calculate the folding energy changes (∆∆G) caused by missense mutations and analyzed the mutations involved in post-translational modifications (PTMs). RESULTS: Our results showed that the functional important missense mutations occurred in the heme peroxidase domain. Through computational saturation mutagenesis, we identified the TPO mutations in G393 and G348 affecting protein stability and PTMs. Our folding energy calculations revealed that seven of nine somatic thyroid cancer mutations destabilized TPO. CONCLUSION: These findings highlight the impact of these specific mutations on TPO stability, linking them to thyroid cancer and other genetic thyroid-related disorders. Our results show that computational mutagenesis of proteins provides a quick insight into rare mutations causing Mendelian disorders and cancers in humans. The effects of TPO mutations linking to thyroid cancer and disorders found via computational mutagenesis. [ABSTRACT FROM AUTHOR]

The article discusses a case of a 9-year-old boy with congenital hypothyroidism who was later diagnosed with sublingual thyroid ectopy. The boy had no significant symptoms until throat discomfort at age 9, prompting further investigation. The article highlights the importance of early detection and management of congenital hypothyroidism, as well as the need for careful consideration of surgical intervention in cases of obstructive symptoms or malignant transformation in ectopic thyroid conditions. [Extracted from the article]

Purpose: We compared the age at menarche and standard deviation score (SDS) of final height (FH) in permanent congenital hypothyroidism (CH) patients with those of healthy female adolescents and assessed their associations with CH screeningrelated variables or demographic factors. Methods: In this cross-sectional study, we included 207 female CH patients and 598 healthy age-matched female adolescents. Ages at puberty onset and menarche, height at puberty and menarche, and the FH and its SDS were evaluated in the 2 groups and compared. Associations between screening variables and anthropometric data with age at menarche and SDS of FH were also assessed in CH patients. Results: In the included population, 113 patients with CH and 453 healthy girls attained their FH. The mean ages at puberty onset and menarche in CH patients were higher than those in the healthy population (P<0.05). The mean height at menarche and the FH and its SDS were not different between the 2 groups (P>0.05). There was no significant association between FH SDS in CH patients and age of treatment (P=0.30). Age at menarche was significantly higher in CH patients with delayed age at treatment initiation (P=0.04). The difference between FH and target height was not significantly different among CH patients (P=0.83). Conclusion: While CH patients had a significantly higher age at menarche compared to the healthy population, appropriate treatment changed this age to be similar to that in the healthy group. However, CH patients who experienced delayed treatment had a higher age at menarche. Age at treatment initiation was the only screening-related variable related to age at onset of menarche and puberty. [ABSTRACT FROM AUTHOR]

Congenital hypothyroidism (CH) is a major health issue that can lead to intellectual disability if not detected and treated earlier. The preliminary screening program for neonatal CH in Indonesia gave a provisional incidence of 1:2513. Newborn screening using a dried blood spot sample is the standard method for CH detection, but it has limitations. Despite the proven benefits of CH screening, Indonesia still faces significant challenges in implementing a nationwide program. This study aimed to develop a more sensitive and accessible screening method by creating monoclonal antibodies (mAbs) against the thyroid-stimulating hormone (TSH).TSH protein was isolated from newborn cord blood and confirmed by Western blot analysis. Mice were immunized with purified TSH, and hybridoma cell lines were generated through cell fusion. Hybridoma supernatants were screened for TSH-specific antibodies using ELISA. The mAb with the highest titer was purified by dialysis. Western blot analysis confirmed the presence of TSH in the isolated protein fraction at 28 kDa. Immunized mice showed a significant increase in antibody titer compared with the control group. Hybridoma clones secreting high-titer antibodies against TSH were identified. This research successfully isolated TSH and produced mAbs against it. They enable the development of rapid, point-of-care diagnostic tests, such as lateral flow immunoassays, which can provide results within minutes. It will lay the groundwork for the development of innovative CH screening tools that can significantly improve the early diagnosis and treatment of this condition, particularly in resource-limited settings. [ABSTRACT FROM AUTHOR]

Context Congenital hypothyroidism (CH) is the most common endocrine disorder in neonates, but its etiology is still poorly understood. Objective We performed whole exome sequencing to identify a novel causative gene for CH and functional studies to validate its role in the occurrence of CH. Methods Whole exome sequencing in 98 CH patients not harboring known CH candidate genes and bioinformatic analysis were performed. Functional analysis was performed using morpholino, a synthetic short antisense oligonucleotide that contains 25 DNA bases on a methylene morpholine backbone, in zebrafish and CRISPR-Cas9-mediated gene knockout in mice. Results Eukaryotic translation initiation factor 4B (EIF4B) was identified as the most promising candidate gene. The EIF4B gene was inherited in an autosomal recessive model, and 1 patient with thyroid dysgenesis carried EIF4B biallelic variants (p.S430F/p.P328L). In zebrafish, the knockdown of eif4ba/b expression caused thyroid dysgenesis and growth retardation. Thyroid hormone levels were significantly decreased in morphants compared with controls. Thyroxine treatment in morphants partially rescued growth retardation. In mice, the homozygous conceptuses of Eif4b +/− parents did not survive. Eif4b knockout embryos showed severe growth retardation, including thyroid dysgenesis and embryonic lethality before E18.5. Conclusion These experimental data support a role for EIF4B function in the pathogenesis of the hypothyroid phenotype seen in CH patients. Our work indicates that EIF4B was identified as a novel candidate gene in CH. EIF4B is essential for animal survival, but further studies are needed to validate its role in the pathogenesis of CH. [ABSTRACT FROM AUTHOR]

Hypothyroidism causes a wide spectrum of clinical manifestations, with various signs and symptoms. Some symptoms are common and aid in diagnosis, while the uncommon manifestations may be the sole feature causing diagnostic delays, leading to increased morbidity and mortality. Hereby the authors present a combination of three cases (50-year-old female, 22-year-old female, 56-year-old female): ascites, congenital hypothyroidism and myxoedema coma, respectively. Ascites in hypothyroidism responds to treatment and can help avoid unnecessary investigations; however, since this presentation is rare, clinicians should remain alert for low Serum Ascites Albumin Gradient (SAAG) with high protein ascites. myxoedema coma was diagnosed after excluding cerebrovascular accident, sepsis and dyselectrolytemia, with low body temperature serving as a diagnostic clue. Congenital hypothyroidism should be identified and treated promptly to prevent complications in newborns, as thyroid hormone is crucial for growth and development. Deficiency may lead to severe complications in newborns, so it is essential to rule out other causes. The importance of the present case series lies in the fact that hypothyroidism may present with variable manifestations. It is crucial to identify this hormone deficiency, as replacement with widely available thyroid hormone supplementation can promptly reverse some of the clinical manifestations, thereby aiding in accurate diagnosis and timely management with appropriate therapy.

Introduction: Congenital hypothyroidism (CH) is the most common preventable cause of mental retardation, and the two important causes of CH are thyroid dysgenesis and dyshormonogenesis. Thyroid imaging is an integral part of identifying the specific aetiology of CH. We aimed to study the aetiological profile of CH and compare the imaging findings of ultrasonography (USG) and nuclear scintigraphy. Methods: It is a prospective, cross-sectional study conducted over 3 years. The clinical, USG, and technetium-99 m (99 mTc) scintigraphy reports of CH children were analysed. Results: Sixty-two CH children were included in the study with an equal male-to-female ratio (1.1:1). There was a significant association between parental consanguinity and CH observed in 35.5% of cases (P = 0.006). In USG neck, 44 (71%) had normal and/or enlarged thyroid glands at the eutopic location, 16 (27.4%) cases had an absent gland, and ectopic as well as hypoplastic unilateral gland was observed in one (1.6%) each. Among 35 children, who underwent scintigraphy, 12 (34.3%) had absent uptake, 4 (11.4%) had ectopic uptake, and 1 (2.8%) child had unilateral normal uptake. The remaining 18 (51.5%) children, whose scintigraphy showed normal or avid uptakes, were diagnosed with dyshormonogenesis. Three cases were diagnosed as apparent athyreosis. Conclusion: Dyshormonogeneis is the more commonly observed etiology of CH as compared to thyroid agenesis in the present study. A combined imaging approach with scintigraphy and USG is needed to delineate the specific etiology of CH. We need long-term Indian data to know the paradigm shift in the etiological pattern of CH as compared to Western studies.

Abstract Background Congenital hypothyroidism (CH) is one of the most prevalent preventable cause of mental retardation and intellectual disability in newborns. Genetic and environmental factors have been related to congenital hypothyroidism. Hence, this study was conducted to illustrate the incidence and spatial distribution of the CH using the dataset from the national newborn CH screening information system during 2011-2020in counties affiliated to the Kohgiluyeh and Boyer Ahmad University of Medical Sciences. Methods This was a cross-sectional study. All newborns that were screened for CH in 3–5 days of age in the health centers of Yasuj University of Medical Sciences were enrolled the study since 2011–2020. Meteorological data including information on temperature, humidity, precipitation in a 10-year period (2011–2020) was taken from the Meteorological Organization. The required information layers include slope, slope direction, height, vegetation and political divisions of the province, were purchased from the organizations that made the layers. The data related to the incidence of congenital hypothyroidism was collected from the 10-year reports of the provincial health center. Addresses of patients were transferred to Arc GIS 10.5 software and entered in urban and rural point’s layer to prepare and draw disease distribution maps in the province’s newborns. The influence of geographical factors on the occurrence of disease was done by SPSS 23 software using multivariate binary logistic regression. P-value

Objectives: The incidence of congenital hypothyroidism (CH) has increased worldwide over the last decades, mainly due to the lowering of screening thresholds, resulting in the increased identification of newborns with transient CH. Several studies have reported the prevalence and the predictive parameters of transient CH, but reports on the long-term outcome are rare. This study aimed to assess the long-term course of neonates with transient CH. Design: Neonates diagnosed with transient and permanent CH between the years 1998 and 2018 at the Pediatric Endocrine Institute of Ha’Emek Medical Center were enrolled in the study. Data were retrieved retrospectively from medical files. Results: A total of 76 newborns (45M, 59%) with transient CH and 53 (25M, 47%) with permanent CH were included in the study. The major causes of transient CH were prematurity (29%) and subclinical hypothyroidism (30%). During retrospective follow-ups of up to 23 years, reinitiation of levothyroxine therapy was not required, apart from four patients with underlying syndromic etiologies. Neurodevelopmental impairment occurred in 16% of children with transient CH compared with 29.4% in the permanent CH group. Conclusions: Transient CH is frequent among preterm infants but is generally limited to infancy. Subclinical hypothyroidism frequently presents as overt hypothyroidism at birth, but in most cases, the requirement for levothyroxine supplemental therapy is limited to the first years of life, suggesting that long-term follow-up of thyroid function tests may be unnecessary for non-syndromic children. The high rate of neurodevelopmental impairment in newborns with transient CH emphasizes the need for neurodevelopmental monitoring in these patients. Significance statement A high rate of transient CH has been identified over the past decades following the lowering of TSH screening thresholds. The long-term outcome of transient CH has been evaluated in a few studies with inconclusive results. In the current study, we assessed the long-term outcomes of transient CH for up to 23 years. We found that 29% of cases were attributed to prematurity and 30% to subclinical hypothyroidism. No morphological anomalies were identified. Only syndromic patients (three with Down syndrome and one with Coffin-Lowry syndrome) required levothyroxine supplemental therapy at the time of the study, indicating that long-term thyroid function monitoring may be unnecessary. The high prevalence of neurodevelopmental impairment suggests the need for close neurodevelopmental monitoring in this population.

Congenital hypothyroidism (CH), characterized by insufficient thyroid hormone production due to abnormalities in the hypothalamic-pituitary-thyroid axis, is the most common congenital endocrine disorder. We previously conducted comprehensive genetic screening of 102 patients with permanent CH born in Kanagawa Prefecture, Japan and identified mutations in several genes in 19 CH patients, including defects in genes encoding dual oxidase 2, thyroglobulin, thyrotropin receptor, thyroid peroxidase, and paired-box 8. Despite these findings, approximately 80% of cases remain unexplained. CH pedigrees unexplained by known genetic forms of CH have been reported in the literature and registered as congenital hypothyroidism, nongoitrous, 3 (CHNG3; %609893) in Online Mendelian Inheritance in Man. We also identified a Japanese pedigree of CH that was compatible with CHNG3. However, the exact genetic cause of CHNG3 was not revealed by standard analysis methods such as exome sequencing and array comparative genomic hybridization. We therefore took a combined approach and analyzed a total of 11 undiagnosed CH pedigrees by whole genome sequencing to analyze a 3-Mb linkage region, and found a disease-causing variant affecting a TTTG microsatellite in a noncoding region on chromosome 15. Further analysis revealed that 13.9% of 989 Japanese CH patients had abnormalities involving the TTTG microsatellite, with a substantial proportion (41.5%) of familial CH cases carrying these mutations. Identification of the genetic cause of CHNG3 provides new insights into the pathogenesis of CH, and highlights the need for continued exploration of noncoding genomic regions in Mendelian disorders of unknown etiology.

Abstract This study aims to examine TPO gene mutations in congenital hypothyroidism (CH) within consanguineous Iranian Azeri families. Three families were subjected to next-generation sequencing and were subsequently validated using Sanger sequencing. The investigation revealed three homozygous pathogenic variants, one of which was identified as a novel variation, occurring within the TPO gene. These findings emphasize the notable prevalence of TPO gene mutations in Iranian Azeri affected by CH, thus establishing the pathogenic nature of the newly discovered variation in the studied patients.

Dyshormonogenesis (DG) is the failure of thyroid hormone production due to a defect in thyroid hormonogenesis. Loss-of-function mutations in the thyroglobulin (TG) gene are a cause of DG, leading to gland stimulation by thyroid-stimulating hormone (TSH), resulting in goiter. We report a mitotically active follicular nodule in an 11-year-old female with a novel mutation in the TG gene. The patient had been under follow-up for congenital hypothyroidism (CH) since the neonatal period, and she had normal TSH levels on replacement therapy. Genetic test revealed a novel compound heterogeneous mutation [c.2149C>T (p.R717*) (P.Arg717Ter) / c.5361_5362delCCinsG (p.H1787Qfs*3) (p.His1787GlnfsTer3)] in the TG gene. She underwent total thyroidectomy for a thyroid nodule that was reported as Bethesda IV on fine needle aspiration biopsy (FNAB) and noted as suspicious for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Pathological examination revealed a 16 mm, well-demarcated follicular nodule with a solid/insular pattern. Mitotic activity and Ki67 proliferation index were unusually high (10 mitoses/mm2 and 10%, respectively). Marked cellular pleomorphism and nuclear atypia are well-known diagnostic pitfalls in patients with dyshormonogenetic goiter. However, high mitotic activity is a feature that is less commonly reported in dyshormonogenetic goiter and may raise suspicion of poorly differentiated carcinoma when observed together with a solid pattern. The absence of signs of invasion, history of CH, and awareness of the presence of mutations compatible with dyshormonogenetic goiter can prevent the overinterpretation of such lesions. The risk of cancer development in the dyshormonogenetic thyroid gland is possible in childhood. The close follow-up is life-saving and prevents morbidities and possible mortality.

Background: Congenital hypothyroidism (CH) is one of the most prevalent preventable cause of mental retardation and intellectual disability in newborns. Genetic and environmental factors have been related to congenital hypothyroidism. Hence, this study was conducted to illustrate the incidence and spatial distribution of the CH using the dataset from the national newborn CH screening information system during 2011-2020in counties affiliated to the Kohgiluyeh and Boyer Ahmad University of Medical Sciences. Methods: This was a cross-sectional study. All newborns that were screened for CH in 3–5 days of age in the health centers of Yasuj University of Medical Sciences were enrolled the study since 2011–2020. Meteorological data including information on temperature, humidity, precipitation in a 10-year period (2011–2020) was taken from the Meteorological Organization. The required information layers include slope, slope direction, height, vegetation and political divisions of the province, were purchased from the organizations that made the layers. The data related to the incidence of congenital hypothyroidism was collected from the 10-year reports of the provincial health center. Addresses of patients were transferred to Arc GIS 10.5 software and entered in urban and rural point's layer to prepare and draw disease distribution maps in the province's newborns. The influence of geographical factors on the occurrence of disease was done by SPSS 23 software using multivariate binary logistic regression. P-value < 0.05 was assumed as significant level. Results: Out of 142,674 screened newborns for CH, 827 had positive screening, including 441 boys (53.3%) and 386 girls (46.7%). Total incidence per 1000 live birth was 5.79. Based on multivariate logistic regression, slope (sig = 0.0001, Exp(B) = 0.91, CI95% Exp(B) = 0.87–0.95), thin forest (sig = 0.001, Exp(B) = 0.2, CI95% Exp(B) = 0.07–0.53), water area (sig = 0.0001, Exp(B) = 8.91, CI95% Exp(B) = 3.35–23.69), were predicting factors of CH. Conclusion: Given that, the incidence of CH in the Kohgiluyeh and Boyar Ahmad province is higher than the average of country (Iran), and the geographical factors of land slope and type of vegetation were related to it that cannot be changed, it is very important to carry out necessary nutritional interventions during pregnancy to prevent newborns from contracting this disease. [ABSTRACT FROM AUTHOR]

INTRODUCTION: One of the most common endocrinological diseases in pregnant women is autoimmune thyroid pathology. It is associated with important maternal, fetal and neonatal complications. OBJECTIVE: To describe the characteristics and impact of maternal autoimmune thyroid disease in newborns. MATERIALS AND METHODS: Observational, longitudinal, descriptive and retrospective study of 200 newborns who's mothers suffered from autoimmune thyroid pathologies for the period spanning from January 2019 to December 2020. RESULTS: 6.64% had autoimmune thyroid pathology. 66.5% presented autoimmune thyroid disease prior to pregnancy and with a diagnosis of hypothyroidism in 83.5%. 33.5% developed thyroid alteration during pregnancy, with a diagnosis of hypothyroidism in 97%. The mean value of maternal hormones was: median TSH: 3.14 mIU/ml; mean T4: 0.79 ± 0.17 ng/dl. In neonates the mean hormone levels at 15 days of life were: TSH: 4.16 ± 2.26 mIU/ml; T4: 1.2 ± 0.19 ng/dl. Three patients (children who's mothers had autoimmune hypothyroidism) were diagnosed with congenital hypothyroidism. CONCLUSIONS: The implementation of a standard actuation protocol, complementary to neonates screening, becomes necessary. [ABSTRACT FROM AUTHOR]

Congenital hypothyroidism can cause lower intellectual abilities in children, which is caused by a lack of thyroid hormone while still in the womb. Data from medical records at the RSCM in Jakarta, Indonesia, and the RSHS in West Java, Indonesia, children's endocrine clinics in 2012-2013 shows that more than 70% of congenital hypothyroidism sufferers were detected after the age of 1 year, so that patients had experienced permanent lower intellectual abilities, so early detection of congenital hypothyroidism is very important. According to the 2014 Minister of Health Decree, the neonatal TSH examination is a sensitive examination for detecting primary congenital hypothyroidism using the Dissociation Enhanced Lanthanide Fluoro Immuno Assays (DELFIA) method at the age of the baby, 24 to 72 hours after birth. The method used in writing this scientific article is article literature. This examination is very important to early detection of congenital hypothyroidism because the late diagnosis of congenital hypothyroidism can cause permanent intellectual instability in children with an average IQ value below 70. Neonatal TSH levels of less than 20 U/mL are normal, while Neonatal TSH levels of ≥ 20 U/mL show a high result and must be confirmed by T4 and FT4 examination. If the neonate's TSH level is high accompanied by an increase in T4 or low FT4 levels, then a diagnosis of primary congenital hypothyroidism can be made. Neonatal TSH examination for newborns is very important to prevent permanent lower intellectual abilities in children. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the combined administration of propylthiouracil (PTU) and levothyroxine (LT4) in managing monocarboxylate transporter 8 (MCT8) deficiency and identify optimal therapeutic dosages. Methods: This multicenter case series involved 12 male patients with MCT8 deficiency whose parents/guardians consented to PTU and LT4 treatment. Data were collected from January 2008 to June 24, 2024. The study focused on treatment safety and outcomes, analyzing baseline and last encounter biochemical, metabolic, and anthropometric parameters. Statistical analyses included Wilcoxon signed ranks tests and generalized estimated equations to assess effects on thyroid and metabolic markers, and receiver operating characteristics curves to predict optimal dose. Results: Patients showed a significant reduction in serum total triiodothyronine (TT3) concentration and TT3/TT4 ratio, with increased serum TT4 and free T4 (fT4) concentrations. The use of PTU effectively reduced TT3 concentration by 25% at an average dose of 6.8 mg/kg/day, while LT4 increased fT4 concentration by 40% from baseline at an average dose of 4.3 µg/kg/day. Thyrotropin concentration was undetectable on treatment. No statistical differences were observed in metabolic and physical parameters between baseline and last encounter overall for the group, but six of eight patients for whom these data were available had an increase in weight (z-score). There were no adverse effects on liver function or granulocyte numbers noted throughout the period of observation. Conclusion: Combined treatment with PTU and LT4 normalized serum T3, fT4, and TT4 in patients with MCT8 deficiency. Individualized dose adjustments were crucial for achieving therapeutic goals, indicating the need for personalized treatment plans. [ABSTRACT FROM AUTHOR]

The document presents research abstracts from the 34th ECVIM-CA Congress in Lyon, France, covering various topics in veterinary internal medicine. The studies explore areas such as echocardiography in cats, risk factors for death in cats with hepatic lipidosis, and antimicrobial prescribing practices in canine acute diarrhea. Additionally, research on bronchoalveolar lavage in dogs and cats, the effects of pimobendan on echocardiographic parameters in dogs with MMVD, and the prevalence of feline blood pathogens in blood donor cats are discussed. The findings offer valuable insights into veterinary medicine practices and contribute to the understanding of various health conditions in animals. [Extracted from the article]

Aim Methods Results Conclusion This study aimed to assess the cognitive development of individuals with congenital hypothyroidism.Using hospital records, we identified 180 patients with congenital hypothyroidism born between 1980 and 2018 in Turku and Kuopio University Hospital catchment areas. Cognitive development was evaluated in 22 adults (7 males and 15 females) and 20 children (8 males and 12 females) using age‐specific Wechsler Intelligence Scales. Full‐scale IQ (FSIQ) and the four indices were compared to standardisation samples. Simple linear regression was used to test whether treatment‐related variables predicted FSIQ.FSIQ and its four indices differed significantly from the standardisation sample in adults with congenital hypothyroidism (FSIQ 87.64, SD 13.70, p < 0.001) but not in children (FSIQ 97.90, SD 15.12). Adults had received a lower initial levothyroxine dose than children (8.1 mg/kg, 95% CI 7.2–9.0 vs. 10.2 mg/kg 9.7–10.7, p < 0.001), and their treatment was initiated later (4.8 days, 95% CI 4.0–5.6 vs. 3.6 days, 2.9–4.2, p = 0.018).Adults with congenital hypothyroidism had a significantly lower FSIQ compared to the population standard, while children's FSIQ did not differ. Our findings suggest that a higher initial levothyroxine dose together with very early treatment start may lead to better cognitive outcomes. [ABSTRACT FROM AUTHOR]

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Introduction: Congenital hypothyroidism (CH) is the most common preventable cause of mental retardation, and the two important causes of CH are thyroid dysgenesis and dyshormonogenesis. Thyroid imaging is an integral part of identifying the specific aetiology of CH. We aimed to study the aetiological profile of CH and compare the imaging findings of ultrasonography (USG) and nuclear scintigraphy. Methods: It is a prospective, cross-sectional study conducted over 3 years. The clinical, USG, and technetium-99 m (99 mTc) scintigraphy reports of CH children were analysed. Results: Sixty-two CH children were included in the study with an equal male-to-female ratio (1.1:1). There was a significant association between parental consanguinity and CH observed in 35.5% of cases (P = 0.006). In USG neck, 44 (71%) had normal and/or enlarged thyroid glands at the eutopic location, 16 (27.4%) cases had an absent gland, and ectopic as well as hypoplastic unilateral gland was observed in one (1.6%) each. Among 35 children, who underwent scintigraphy, 12 (34.3%) had absent uptake, 4 (11.4%) had ectopic uptake, and 1 (2.8%) child had unilateral normal uptake. The remaining 18 (51.5%) children, whose scintigraphy showed normal or avid uptakes, were diagnosed with dyshormonogenesis. Three cases were diagnosed as apparent athyreosis. Conclusion: Dyshormonogeneis is the more commonly observed etiology of CH as compared to thyroid agenesis in the present study. A combined imaging approach with scintigraphy and USG is needed to delineate the specific etiology of CH. We need long-term Indian data to know the paradigm shift in the etiological pattern of CH as compared to Western studies. [ABSTRACT FROM AUTHOR]

Objective: To assess the parental stress, coping mechanism and quality of life of caregivers of children with Differences of Sex Development (DSD). Methods: Mothers of children (6 months - 12 years) with DSD were enrolled after excluding mothers of children with syndromic diagnosis, developmental delay, cognitive impairments, chronic diseases, or if the duration of DSD diagnosis was less than six months, and mothers with psychiatric illnesses (n = 35). Mothers of age and gender-matched children with congenital hypothyroidism served as controls (n = 35). Psychological assessments were performed using structured questionnaires: the Parent Stress Scale, PRIME MD PHQ-9 Scale, and Ways of Coping Questionnaire. Results: Mothers of children with DSD exhibited significantly higher mean (SD) stress levels [24.34 (4.25) vs 19.57 (1.89); P < 0.001]. Prevalence of depression prevalence was higher in mothers in the DSD group than in the hypothyroidism group (71% vs 42.9%, P < 0.001). Mothers of children with DSD also had poorer quality of life, and both high negative coping behavior and low positive coping behavior (P < 0.001) compared to controls, and stigma related to social exclusion was more pronounced. Conclusions: Beyond medical interventions, addressing family members' psychological well-being is essential in effectively managing DSD in the Indian context. [ABSTRACT FROM AUTHOR]

This study aims to examine TPO gene mutations in congenital hypothyroidism (CH) within consanguineous Iranian Azeri families. Three families were subjected to next-generation sequencing and were subsequently validated using Sanger sequencing. The investigation revealed three homozygous pathogenic variants, one of which was identified as a novel variation, occurring within the TPO gene. These findings emphasize the notable prevalence of TPO gene mutations in Iranian Azeri affected by CH, thus establishing the pathogenic nature of the newly discovered variation in the studied patients.Article highlights: Identification of Novel Mutation: A novel TPO gene mutation, c.613G>A; p.(Val205Ile), was discovered, potentially contributing to the pathogenesis of CH. Role of TPO Mutations: Evidence suggests that TPO gene mutations are one of the major genetic factors leading to congenital hypothyroidism (CH) in the study population with consanguineous marriages. Genetic Insights into CH: The study uncovers three pathogenic TPO gene mutations in Iranian Azeri families, understanding of congenital hypothyroidism's genetic basis. [ABSTRACT FROM AUTHOR]

Background: NKX2-1, a crucial transcription factor in thyroid, lung, and brain development, is associated with rare disorders featuring thyroid dysfunction, neurological abnormalities, and respiratory symptoms. The primary challenge in managing NKX2-1-related disorders (NKX2-1-RD) is early diagnosis of the genetic defect and treating specific endocrine disorders. Levothyroxine (LT4) serves as the standard hypothyroidism treatment, with required dosages influenced by the severity of the individual's disorder, which varies widely among affected individuals. Objectives: This systematic review aims to assess the effectiveness of LT4 treatment in NKX2-1-RD and explore optimal dosing strategies. The primary focus is on the challenges associated with the prompt diagnosis of genetic defects, rather than the established treatment protocols for individual endocrine failures. Methods: Adhering to PRISMA guidelines, the review includes 42 studies involving 110 genetically confirmed NKX2-1-RD patients with hypothyroidism. The study investigates congenital hypothyroidism as the most prevalent endocrine alteration, along with gestational and overt hypothyroidism. The administration of LT4 treatment, dosages, and patient responses are analyzed. Results: Among the findings, congenital hypothyroidism emerges as the predominant endocrine alteration in 41% of patients. Notably, LT4 treatment is administered in only 10% of cases, with a mean dose of 52 μg/day. The variability in initiation and dosage is likely influenced by the age at diagnosis. Positive responses, characterized by TSH adjustments within normal ranges, are observed in 11 monitored patients. Conclusions: Early detection of congenital hypothyroidism is emphasized for timely LT4 initiation. Challenges in standardization are highlighted due to the variability in clinical manifestations and diagnostic procedures across NKX2-1-RD cases. While this review provides valuable insights into thyroid and pituitary disease treatment, limited details on LT4 treatment represent a significant study limitation. Key reporting points for future case studies are proposed to enhance the understanding and management of NKX2-1-RD hypothyroidism. [ABSTRACT FROM AUTHOR]

Background: Over the past two decades, the incidence of thyroid disorders has been steadily increasing. There is evidence to suggest that air pollution may be one of the etiological factors of thyroid diseases. This comprehensive review aimed to examine the evidence related to air pollutants and thyroid disorders and thyroid hormones levels from an epidemiological perspective. Methods: The scoping review adopted a systematic approach to search for, identify, and include peer-reviewed articles published in English. We performed a comprehensive search of three databases-PubMed, Embase, and Web of Science to identify relevant literature on the relationship between air pollution [particulate matter, nitrogen oxide, carbon monoxide (CO), ozone (O3), sulfur dioxide (SO2)] exposure and thyroid disorders, including hypothyroidism, congenital hypothyroidism (CH), thyroid nodules, thyroid cancer, autoimmune thyroid diseases, as well as thyroid hormone levels, such as thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4). Articles published until August 1, 2023, were included. Results: A total of 3,373 studies were retrieved, and among them, 25 studies covering eight different air pollutants were relevant. The most frequently studied air pollutants in this review included fine particulate matter (with fine particulate matter (PM2.5), n=21; inhalable particles (PM10), n=10; PM10-2.5, n=1) and nitrogen oxides (with NO2, n=13; NOx, n=3). The thyroid disorders and thyroid hormone levels most commonly associated with evidence of air pollution exposure were hypothyroidism (n=7) and TSH (n=12). Conclusions: Despite variations in study designs and exposure assessments, the findings consistently highlight the substantial health risks that air pollution, particularly PM2.5, poses to thyroid health, especially among vulnerable populations. Given that our study was limited to epidemiological investigations and the increasing prevalence of toxic substances in the environment, there is an urgent need for further research to elucidate the mechanisms by which these pollutants disrupt thyroid function and contribute to the development of thyroid diseases. [ABSTRACT FROM AUTHOR]

Introduction: Pathogenic variants in the genes involved in the formation of thyroid tissue and thyroid hormone secretion have been reported to cause congenital hypothyroidism (CH) in some cases. This study aimed to evaluate the clinical and genetic findings of CH cases thought to be due to genetic variants. Methods: The study included cases whose genetic analysis was performed in accordance with the Congenital Hypothyroidism: A 2020–2021 Consensus Guidelines Update Guidelines recommendations criteria and analyzed them using the next-generation sequencing panel. Results: Sixty one Turkish patients from 45 families were included in the study. The overall frequency of variant detection was 37.7% (out of 45 families, 17 had a positive mutation). Segregation was carried out for all families with positive variants. Variants in the TPO gene are the most frequently encountered, and this situation was identified in 10 families. Variants followed this in the TSHR gene in 7 families, variants in the DUOX2 gene in 5 families, and two variants in the TG and NKX2-1 genes in 2 families each, which are six novel variants. Furthermore, among the NKX2-1 cases, one had thyroid involvement only, while the other had chorea only. We did not find differences between cases with detected mutations and mutation-negative cases regarding gender, neonatal/perinatal parameters, initial thyroid function values, and thyroid morphology. Conclusion: In the current investigation, rare new variations in genes known to be related to CH were discovered, adding to the molecular genetic spectrum. When we compare the overall variant detection frequency, the selection criterion for genetic analysis based on the current guidelines is quite rational, considering the benefits and costs, on the other hand, present in new genes awaiting discovery. Also, TSHR mutations are likely to be common and may account for more than 5% of thyroid dysgenesis cases if we include nonfamilial thyroid dysgenesis. [ABSTRACT FROM AUTHOR]

Background: Climate change has many effects on various aspects of human life, including health. Iran is highly vulnerable to climate changes, which can have a significant impact on public health. Therefore, this study aims to review the effects of climate change on public health in Iran. Materials and Methods: This systematic study was conducted based on the preferred reporting items for systematic reviews and meta-analysi (PRISMA) protocol and three steps of search, screening, and synthesis of selected studies. To identify related studies published from 2000 to 2023, online databases (PubMed, Scopus, Web of Science, MagIran, and SID) were searched using relevant keywords. Finally, we selected 52 eligible studies. The selected studies were screened to extract key information. Results: The direct effects of climate change included the increase in infectious, cardiovascular, and respiratory diseases, changes in women's pregnancy patterns, and the prevalence of preeclampsia, skin cancer, pterygium, congenital hypothyroidism, and mortality. Indirect effects of climate change included the changes in reproductive patterns and the spread of insect-borne and human diseases such as malaria, brucellosis, leishmaniasis, human salmonellosis, cholera, bloody diarrhea, Crimean-Congo hemorrhagic fever (CCHF), and COVID-19. Moreover, climate change had negative impact on the mental health such as increased mood swings, depression, schizophrenia and schizoaffective disorders, and bipolar disorder. The results showed that vulnerability to climate change varies depending on geographical and demographic factors. Conclusion: Climate change has many adverse effects on the physical and mental health of Iranian people; therefore, the development and implementation of national strategies and programs to fight against them are essential. Despite studies conducted so far on the relationship between climate change and human health in Iran, there is still a need for further investigations, especially regarding the connection between climate change and people's mental health. [ABSTRACT FROM AUTHOR]

Background/Objectives: There is evidence of overtreatment in patients with subclinical hypothyroidism (SCH). We aimed to identify the proportion of patients treated for SCH and the determinants of thyroid hormone therapy initiation. Methods: We included a random sample of adult Veterans diagnosed with SCH from 1 January 2016 to 31 December 2018 and conducted univariate and multivariable logistic regression to identify factors associated with levothyroxine initiation. Results: Out of 229 Veterans with SCH [90.0% male, 87.2% White, 99.1% non-Hispanic, median age (interquartile range; IQR) 68 (17) years], 27.5% were treated with levothyroxine. The treated group had a higher proportion of White patients (95.2% vs. 84.2%, p = 0.039), a higher thyrotropin level [median (IQR), 6.98 (2.06) mIU/L vs. 6.14 (1.10) mIU/L, p = 0.0002], a higher proportion of patients with thyrotropin level ≥ 10 mIU/L (11.1% vs. 3.0%, p = 0.021), a lower frequency of confirmatory thyroid testing before initiating levothyroxine (49.2% vs. 97.0%, p < 0.0001), and a similar frequency of thyroid autoimmunity testing (3.2% vs. 0.6%, p = 0.18) compared to the untreated group. In a multivariable logistic regression analysis, White race (OR = 4.50, 95% CI 1.19 to 17.08, p = 0.026) and index thyrotropin level [OR = 1.71, 95% CI 1.24 to 2.35, p = 0.001; for every SD increase (1.6 mIU/L)] were associated with higher odds of treatment. Conclusions: Three in 10 Veterans with SCH received levothyroxine, often based on a single abnormal thyroid test without autoimmunity assessment. White race and higher thyrotropin level were linked to increased odds of starting treatment, indicating potential disparities and the influence of SCH severity on decision-making. [ABSTRACT FROM AUTHOR]

Background: Patients treated for hypothyroidism with levothyroxine (LT4) monotherapy may present with persistent hypothyroidism symptoms, including cognitive symptoms, despite having a normal thyroid stimulating hormone (TSH) level. It remains unclear whether LT4 monotherapy is sufficient to normalize cognitive function outcomes over time. Methods: This is a multisite longitudinal study of a diverse group of women during midlife representing 5 ethnic/racial groups from 7 enrollment sites across the United States in the Study of Women's Health Across the Nation. Women were screened for a history of thyroid disease and the use of LT4. The study consisted of two primary groups: women with LT4-treated hypothyroidism and control women without thyroid disease. Each participant completed up to 9 cognitive assessments over the study period testing processing speed, working memory, and episodic memory (immediate and delayed recall). Multivariable generalized linear mixed models of scores for each cognitive assessment were developed to determine the association between LT4-treated hypothyroidism and cognitive function trajectories. Covariates included sociodemographic, clinical characteristics, and menopausal status (pre/early peri, late peri, and surgical/post). Sensitivity analyses were conducted to assess the impact of abnormal TSH levels and practice effects (i.e., improvements in scoring after repeated testing). Results: Of the 2033 women who were included in the study, 227 (11.2%) met criteria for LT4-treated hypothyroidism. At baseline, both processing speed and working memory scores were higher in LT4-treated women (mean processing speed scores: 56.5 vs 54.4; p value = 0.006; mean working memory scores: 6.8 vs 6.4; p value = 0.018). However, when considering the effect of LT4-treated hypothyroidism over time, there were no significant differences in the rate of cognitive decline (in any measure) between the hypothyroidism and control groups with or without covariate adjustment. The results were similar when considering LT4-treated women with abnormal TSH levels or after minimizing practice effects. Conclusions: We observed no difference in cognitive decline between women with LT4-treated hypothyroidism and women without thyroid disease. For similar aged patients with cognitive complaints, if thyroid function testing is normal, clinicians should consider causes other than inadequate thyroid hormone treatment to explain these symptoms. [ABSTRACT FROM AUTHOR]

This document is an interview with Dr. Samuel Refetoff, a renowned thyroid researcher. The interview provides a brief background on Dr. Refetoff's upbringing in Bulgaria and his journey to becoming a medical professional. It also discusses his early work with a family in Los Angeles who had suspected thyroid problems, which eventually led to the discovery of resistance to thyroid hormone. The interview highlights the challenges faced by Dr. Refetoff in getting his ideas accepted and the assistance he received from other experts in the field. Dr. Refetoff describes his research on target tissue resistance to thyroid hormone and the discovery of mutations in the thyroid hormone receptor genes. He also discusses other areas of his research, including thyroxine-binding globulin deficiency and TSH resistance. Dr. Refetoff emphasizes the importance of supporting young researchers in the field of thyroidology and expresses concerns about the lack of funding for studies on congenital thyroid diseases. The conversation concludes with a discussion of Dr. Refetoff's personal life and family. [Extracted from the article]

Importance: There is uncertainty as to whether treatment of subclinical hypothyroidism (SCH) is associated with cardiovascular outcomes. Objectives: To determine whether levothyroxine replacement therapy decreases the risk of major adverse cardiovascular events (MACE) among individuals with SCH defined as having a thyrotropin (TSH) level between 5 and 10 mU/L. Design: We conducted a population-based cohort study using a prevalent new-user design. Setting: The study utilized data from the United Kingdom Clinical Practice Research Datalink. Participants: We identified a base cohort of individuals aged ≥18 years with incident SCH defined as having at least two TSH levels between 5 and 10 mU/L within one year between 1998 and 2018. We matched 76,946 levothyroxine treated to 76,946 untreated individuals based on age, sex, calendar time, duration of SCH, and time-conditional propensity score. We compared individuals with SCH treated with levothyroxine with individuals with no treatment. Exposure: Levothyroxine treatment versus no treatment. Main Outcome Measures: The primary outcome, MACE, was defined as a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular-related mortality. Results: The mean age of the study cohort was 62.8 years, and 76.5% were women. During a median follow-up time of 1.6 years (interquartile range: 0.5–4.2), the incidence rate for MACE among individuals treated with levothyroxine was 12.8 per 1000 person-years; confidence interval (CI): 12.2–13.3 and 13.9 per 1000 person-years; CI: 13.4–14.3 among nontreated individuals. Levothyroxine treatment was associated with a small decreased risk of MACE (hazard ratio: 0.88; CI: 0.83–0.93). Conclusions: Levothyroxine treatment of SCH was associated with a small decreased risk of MACE. However, given the observational nature of the study, residual confounding should be considered in the interpretation of this finding. [ABSTRACT FROM AUTHOR]

To assess the incidence of congenital hypothyroidism (CH) and acquired hypothyroidism (AH) between 2014 and 2019 in continental France. New cases of CH and AH were identified using the French National Health Data System (Système Nationale des Données de Santé, SNDS). Temporal trends were studied using linear regression models. Spatial distributions were studied using Moran's global index (I) and the statistical method and local indicators of spatial association. The incidence of permanent CH in females increased by 8.9 % per year (2014: 36.9 [31.1–43.7] per 100,000 birth-years vs. 2019: 51 [43.9–59.3] per 100,000 birth-years, p < 0.01). The incidence of AH decreased between 2014 and 2019 for both females (2014: 535.7 [533.2–538.2] per 100,000 person-years vs 2019: 335.5 [333.6–337.4] per 100,000 person-years, p < 0.01) and males (2014: 197.5 [195.9–199] per 100,000 person-years vs 2019: 141.7 [140.4–142.9] per 100,000 person-years, p < 0.01). The incidence of hypothyroidism was high in the Nord-Pas-De-Calais and Lorraine regions (CH and AH). The incidence of permanent CH in females has increased over time. AH incidence decreased. It seems necessary to investigate environmental factors in the disparity of incidence distribution. [ABSTRACT FROM AUTHOR]

Background: In Permanent congenital hypothyroidism (PCH) is a lifelong condition characterized by a deficiency in thyroid hormone, leading to various neurodevelopmental complications. Early clinical signs are often nonspecific and easily overlooked, but newborn screening programs have improved early detection. Methods: This narrative review aims to provide insights comparatively transient and permanent PCH and also the diagnosis, risk factors, underlying pathophysiology, and genetic causes associated with PCH. Relevant studies were identified through a comprehensive search using the term 'Permanent congenital hypothyroidism' (Mesh) across scientific databases of electronic databases such as PubMed, Scopus, and Web of Science. Results: Prompt initiation of thyroid hormone replacement therapy, particularly within the initial two weeks postpartum, crucially enhances neurocognitive development outcomes. Multiple predictive approaches, encompassing screening TSH levels, maternal thyroid history, and levothyroxine dosage per kilogram assessment, aid in identifying PCH. Recent studies have demonstrated a mounting prevalence of PCH, contributing significantly to the overall rise in CH incidence. Genetic factors, primarily DUOX2 and DUOXA2 mutations, alongside environmental influences such as postterm birth, low birth weight, and macrosomia, may induce PCH. Nonetheless, reliable markers for early PCH prediction upon diagnosis remain elusive, leading to delayed recognition post-ceasing levothyroxine treatment around age 3. Conclusions: Recent studies have observed an increased incidence of PCH, contributing substantially to the overall rise in cases of congenital hypothyroidism. Understanding the diagnostic options and genetic etiologies associated with PCH is crucial for the early identification and appropriate management. [ABSTRACT FROM AUTHOR]

Genetic defects in the TSH receptor (TSHR) can cause poor thyroid differentiation (thyroid dysgenesis) and/or thyroid malfunction (thyroid dyshormonogenesis). The phenotype spectrum is wide: from severe congenital hypothyroidism to mild hyperthyrotropinemia. Over 250 TSHR variants have been published, many uncharacterized in vitro. We aimed to genetically characterize patients with thyroid dyshormonogenesis with TSHR defects and to study in vitro the effect of the genetic variants to establish the genotype–phenotype relationship. Pediatric patients with thyroid dyshormonogenesis (160 patients, Catalan CH neonatal screening program, confirmation TSH range: 18.4–100 mIU/L), were analyzed by a high-throughput gene panel. In vitro studies measuring the TSH-dependent cAMP–response–element activation were performed. Five patients with mild or severe thyroid dyshormonogenesis presented six TSHR variants, two unpublished. Each variant showed a different in vitro functional profile that was totally or partially deleterious. Depending on the genotype, some of the variants showed partial deficiency in both genotypes, whereas others presented a different effect. In conclusion, the percentage of patients with thyroid dyshormonogenesis and candidate variants in TSHR is 3.13%. Our in vitro studies contributed to the confirmation of the pathogenicity of the variants and highlighted the importance of studying the effect of the patient's genotype for a correct diagnostic confirmation. [ABSTRACT FROM AUTHOR]