Congenital Hypothyroidism Research Articles

Challenges in management of abnormal thyroid function tests in unwell infants: A tertiary centre real-world experience.

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.

To Study the Iodine Concentration of Mothers’ Consumed Salt, Water, and Staple Food in the Neonatal Screening Program of Rural and Urban Vidarbha Region

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.

To Study the Thyroid Hormone Levels in Neonates of Rural and Urban Vidarbha Region

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.

The possible association of two novel heterozygous GNB1 variants with obesity and metabolic disorders.

Variants in the GNB1 gene, which encodes for the beta-1 subunit of G proteins, have been associated with intellectual development disorder (OMIM: 616973), characterized by developmental delay, infantile hypotonia, seizures, and psychiatric problems. GNB1 variants may also cause a multisystem disorder, with symptoms such as hearing and vision impairment, gastrointestinal disorders, genitourinary abnormalities, and growth delay. We present two pediatric patients with two novel GNB1 variants. The first patient is a 12-year old Caucasian European female with a history of neonatal hypotonia, feeding difficulties, and failure to thrive for the first 2 years of life. Subsequently, she developed grade 3 obesity, hyperphagia, and autoimmune thyroiditis. Whole Exome Sequencing (WES) revealed a novel likely pathogenic variant in the GNB1 gene (NM_002074.5:c.93_94del, p.Gln32AspfsTer46), which is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. The second patient is a 2-year old Roma female with severe failure to thrive during infancy, congenital hypothyroidism, and transient hyperoxaluria. No developmental delay was identified. Genetic testing excluded primary hyperoxaluria and WES revealed to be a novel likely pathogenic variant {NM_002074.5:c.183G > T (NP_002065.1:p.Met61Ile), which is predicted to have a damaging effect on the gene or gene product. We present two rare pediatric cases with novel GNB1 variants which highlight the phenotypic variability associated with disrupted GNB1 expression. GNB1 may serve as a candidate gene for severe early onset obesity, hyperphagia, neurodevelopmental delay, and other metabolic and endocrine disorders.

High yield of congenital hypothyroidism among infants attending Children Hospital, Nairobi, Kenya. Facility based study in the absence of newborn screening.

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 3days 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 6weeks 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 TSHand free T4. The incidence of abnormal TSH across the different age groups was 2.4 , 7.2 and 10.5 % for ages 0-29days, 1-11months, 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.

Diagnostic Utility of Cord Thyroid-Stimulating Hormone (TSH) in Congenital Hypothyroidism and Its Association With Perinatal Factors: A Study From a Tertiary Referral Centre in Hyderabad, India

Diagnostic Utility of Cord Thyroid-Stimulating Hormone (TSH) in Congenital Hypothyroidism and Its Association With Perinatal Factors: A Study From a Tertiary Referral Centre in Hyderabad, India

Outcomes of newborns screened for congenital hypothyroidism in Turkey- a single center experience.

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 17days (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 4136480: A Rare Cause of a Classic Presentation of NSTEMI: Case of 39-Year-Old Female with Hypothyroidism Induced Myocarditis

Background: Myocarditis is a cause of non-ischemic cardiomyopathy (NICM) and troponin elevation. There are many causes including uncontrolled thyroid disorder (TD). A thorough history, cardiac MRI (cMRI) followed by an endomyocardial biopsy (EMB) is necessary for diagnosis. This case illustrates a classic presentation of NSTEMI with a rare cause of myocarditis due to uncontrolled hypothyroidism. Description of Case: A 39-year-old female with history of congenital hypothyroidism and tobacco use disorder presented to the Emergency Department with sudden onset of unprovoked sub-sternal chest pain. She stated she had stopped taking her levothyroxine years ago due to side effects such as abdominal discomfort. On admission, work up included high sensitivity troponin (Hs-cTn), EKG, urine drug screen (UDS), and thyroid panel. There was no evidence of ischemic changes on EKG, Hs-cTn was 3600 (normal: 3-54) which up-trended to 43,742, and UDS was negative. She was placed on appropriate medical therapy for NSTEMI and taken for urgent coronary angiography wbich showed normal epicardial arteries. A transthoracic echocardiogram (TTE) was unremarkable with a normal ejection fraction (EF). However, she continued to complain of chest discomfort and palpitations. Her vital signs remained stable but her thyroid panel revealed a TSH of 127 (normal: 0.27-4.2), T4 of 0.18 (normal: 0.92 – 1.6) and T3 of 1.0 (normal: 2.3-4.2). Inflammatory markers were also elevated. A cMRI was obtained revealing gadolinium enhancement in the anterior septal wall with extension into the subepicardium of the inferior wall suggestive of possible myocarditis. An EMB was performed to elucidate etiology. Pathology results were only remarkable for edema but newly reduced EF of 30-35% was noted on TTE at time of biopsy. Endocrinology was consulted for untreated hypothyroidism and patient was initiated on levothyroxine leading to improvement of her symptoms. Discussion: Our patient's history and work up were consistent with myocarditis induced by severe hypothyroidism. TD is a rare cause of reversible NICM and symptoms improve once TD is controlled. While there are several cases reported on hyperthyroidism associated myocarditis, there are only a few cases of myocarditis associated with uncontrolled hypothyroidism. Clinicians should maintain a broad differential to ensure a thorough work up in a patient presenting with NSTEMI, and a thyroid panel should be included especially if myocarditis is suspected.

What is the ideal thyroid-stimulating hormone (TSH) threshold value in congenital hypothyroidism screening? Twin study.

Congenital hypothyroidism is the most common preventable cause of intellectual disability. Therefore, the majority of developed countries have aimed to diagnose cases early through screening programs. In these screening programs, levels of thyroid-stimulating hormone (TSH) and free thyroxine are examined in dried blood spots taken between days 3 and 5 of life. While many countries accept TSH threshold value of 8 mU/L, there is still no consensus on the ideal TSH threshold value. As no twin studies on the TSH threshold value have been conducted previously, this study was planned. Eight pairs of twins were included in the study, with one of the twins having plasma TSH value ≥8 mU/L and the other <8 mU/L, measured between days 3 and 5 of life. The study aimed to investigate whether determining threshold TSH value of 8 mU/L would be beneficial by comparing somatic growth, mental development, and neuromotor development between twins. The age, gender, gestational weeks, birth weights, height, weight, and initial TSH values taken between days 3 and 5 of all cases were recorded. The patients' plasma Vitamin B12, folate, 25-OH Vitamin D, ferritin, and hemoglobin levels were measured. After that, they were evaluated by a child and adolescent psychiatry. Finally, the Denver Developmental Test was applied to the cases. There was no significant impairment in somatic growth, mental development, and neuromotor development in the long-term outcomes of cases with plasma TSH ≥ 8 mU/L compared to those with plasma TSH < 8 mU/L among the twins participating in our study.

CONGENITAL HYPOTHYROIDISM IN NEWBORN AND ASSOCIATION WITH SOCIODEMOGRAPHIC PARAMETERS AMONG NEONATE DELIVERED AT MILITARY HOSPITAL IN A CITY OF CENTRAL INDIA

Objectives: The present study aims to assess the incidence of congenital hypothyroidism (CH) among neonates in a tertiary care hospital in central India, examining its association with various sociodemographic parameters. Methods: This cross-sectional study, conducted between January and December 2022, included all live births at a tertiary care center in Jabalpur, Madhya Pradesh. Cord blood thyroid-stimulating hormone (TSH) levels were measured for all newborns as part of routine screening. Sociodemographic data, including maternal age, gestational age, birth order, and newborn sex, were collected. Universal sampling was employed, encompassing all consenting parents and their neonates. Results: Among 388 live births, TSH values ranged from 0.23 to 35.59 mIU/L, with a mean TSH of 8.76±5.92 mIU/L. Of the neonates, 95.9% had normal TSH levels, while 4.1% exhibited elevated levels. Subsequent follow-up identified CH in two neonates (5.2 per thousand live births). Analysis revealed no significant association between elevated TSH levels and maternal age or newborn sex. However, a significant association was observed with gestational age. Birth order also displayed significance, with the third birth order having a higher proportion of neonates with raised TSH levels. Conclusion: This study highlights the importance of CH screening in preventing long-term complications and the various sociodemographic factors linked to CH, such as maternal age, gestational age, and birth order.

A clinical review of early assessment for congenital hypothyroidism in newborns

Congenital hypothyroidism is a critical factor associated with stunting, as thyroid hormone deficiencies can impair growth starting in utero. Children with thyroid disorders, including conditions like hypoparathyroidism, often experience growth retardation due to congenital abnormalities and growth hormone deficiencies. For neonates, a lack of thyroid hormones can lead to long-term impacts, such as physical and mental disabilities, neurological disorders, and stunted growth. Early detection of congenital hypothyroidism is, therefore, essential and is typically part of newborn screening aimed at identifying congenital abnormalities. Implementing early screening protocols can diagnose and treat congenital hypothyroidism promptly, mitigating risks such as stunting and enabling better health outcomes for children. This literature review examines methods of early detection for congenital hypothyroidism across various global contexts. Three databases—PubMed, ScienceDirect, and Google Scholar—were searched using a systematic literature review approach, yielding five eligible studies with a combined study population of 920.441 newborns. These studies involved screenings for T4, TSH, 17-OHP, and G-6-PD, identifying hypothyroidism in 2.530 (27%) cases. Screening involved blood samples taken from the umbilical cord or heel within 48 to 72 hours after birth. Understanding early detection procedures for congenital hypothyroidism is essential for nurses, as it enables them to engage in early intervention and provide effective nursing care for affected infants. Early involvement can help prevent the adverse, long-term effects associated with congenital hypothyroidism, improving quality of life and supporting healthy growth trajectories for children at risk. Keywords: Congenital hypothyroidism; literature review; nursing assessment; paediatric nursing; prevention

Detection of inborn errors of metabolism: guidelines in Mexico and other countries

Inborn errors of metabolism (IEM), also known as inherited metabolic disorders, are rare but associated with significant morbidity and mortality. The incidence is variable in all regions, worldwide it ranges from 1 in 569 to 2500 live births (LBI). The objective of this work was to carry out a narrative review to identify the guidelines that guide the detection of EIMs through official sources from various countries. A total of 13 documents were identified, including protocols, books, manuals, programs and 4 official websites for the detection of EIMs. In general, there is variability in the selection of EIMs that are detected, from 4 to 61 EIMs, primary congenital hypothyroidism and pheniceltonuria are the two EIMs that are included in most screening programs, spinal atrophy and severe combined immunodeficiency are detected less frequently, the incidence of each EIM is variable between countries and even between states of the same country, with congenital hypothyroidism being the most common. The guidelines for the selection of EIMs are determined by the internal policies of each country, the incidence and economic resources. There is no universal standard for the detection of EIMs, but they all pursue the same purpose: detection, diagnosis and timely treatment. In parallel, it allows us to estimate with greater precision the frequency of these disorders.

Higher initial levothyroxine doses and very early treatment start may lead to better cognitive outcomes in children with congenital hypothyroidism.

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.

Deciphering the mystery of CHNG3.

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.

The Relationship Between TSH and Indirect Bilirubin Levels in Neonates Suspected of Having Jaundice

Background: Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency that occurs at birth. The TSH (thyroid-stimulating hormone) test is crucial for diagnosing hypothyroidism. CH is known to cause prolonged unconjugated hyperbilirubinemia. Therefore, this study aimed to analyze the relationship between TSH and indirect bilirubin levels in neonates suspected of having jaundice. Methods: This is a non-experimental, retrospective study conducted at Lombok Dua Dua Lontar Mother and Child Hospital in Surabaya. The study involved data collection on neonates aged 2–7 days suspected of jaundice, whose TSH and indirect bilirubin levels were measured between November 2022 to April 2024. Results: Among 100 neonates, 62% were aged 2-4 days, while 38% were aged 5-7 days. The majority were male (56%), with female comprising 44%. Of the 100 neonates, only 1 (1%) had borderline TSH levels, while 99% had normal TSH levels. Hyperbilirubinemia was observed in 94% of the neonates, while 6% had normal indirect bilirubin levels. Statistical analysis using the Spearman correlation showed no significant link between TSH and indirect bilirubin levels (p = 0.802). Conclusions: While this study did not find a clear connection between TSH and indirect bilirubin levels in neonates suspected of having jaundice, one case of borderline TSH was identified. This neonate required referral to pediatric endocrinology, as untreated congenital hypothyroidism can lead to mental retardation. Despite limited research linking TSH and bilirubin levels in jaundiced neonates, routine screening for congenital hypothyroidism using TSH testing should be reconsidered. Future studies could benefit from focusing on specific causes of neonatal jaundice to help narrow down research questions in this area.

Systematic review of thyroid function in NKX2-1-related disorders: Treatment and follow-up.

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. 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. 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. 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. 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.

Genetic insights into congenital hypothyroidism in three Iranian Azeri families with consanguineous marriage: the role of novel and recurrent TPO gene variations

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.

Identification and determination of the urinary metabolite of iodotyrosine invivo

BackgroundCongenital hypothyroidism screening traditionally relies on detecting elevated thyroid-stimulating hormone levels, yet this approach may not detect a specific type of congenital hypothyroidism caused by iodotyrosine dehalogenase-1 (Dehal1) deficiency. The deficiency of this enzyme prevents the deiodination of mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) in the process of iodine recycling. This underscores the potential use of iodotyrosine or its metabolites as non-invasive urinary biomarkers for early diagnosis of congenital hypothyroidism. However, the urinary metabolites of MIT/DIT have not yet been discovered. Thus, this study aimed to identify the urinary metabolites of iodotyrosine in experimental models. MethodGas chromatography mass spectrometry was used to identify the urinary metabolites of iodotyrosine following intraperitoneal injection of MIT in rats. An isotope dilution mass spectrometric assay was developed for assessment of identified metabolites. Urine samples from Dehal1 knockout mice were used to confirm the results. ResultsWe identified novel iodotyrosine metabolites, 3-iodo-4-hydroxyphenylacetic acid (IHPA), and 3,5-diiodo-4-hydroxyphenylacetic acid (Di-IHPA) as the primary urinary metabolites of MIT and DIT respectively. The concentrations of urinary IHPA and Di-IHPA were significantly higher in Dehal1 knockout mice. ConclusionOur findings suggest that IHPA is detected in larger quantities and may hold more clinical significance than previously identified biomarkers like MIT and DIT, making it a promising candidate for diagnosing congenital hypothyroidism or other conditions associated with iodine recycling inhibition.

The natural course of newborns with transient congenital hypothyroidism.

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. 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. 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. 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. 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.

Comparison Between Ultrasonography and Radiography in the Detection of Epiphyseal Ossification Centers of the Knee in Infants With Permanent Congenital Hypothyroidism.

To demonstrate the usefulness of ultrasonography in detecting knee ossification centers in infants with permanent congenital hypothyroidism (PCH). From 2011 to 2021, all infants with PCH referred for thyroid ultrasound also underwent left knee ultrasound and radiography on the same day. Knee radiographs were compared with knee sonograms. Two pediatric radiologists reviewed the consensus knee radiographs and sonograms to identify femoral and tibial epiphyseal ossification centers (presence/absence). The concordance between ultrasonography and radiography was assessed. Another radiologist conducted a second late review to evaluate interobserver agreement. We identified 125 patients (65 girls, 60 boys) with a mean age of 24 days (5 days-5 months). On scintigraphy, the thyroid was in place in 66.4%, ectopic in 24%, and absent in 9.6% of patients. The femoral center was observed in 108 patients (86.4%) via sonography and 106 patients (84.8%) via radiography. The tibial center was observed in 84 patients (67.2%) via sonography and radiography. Both femoral and tibial centers were present on sonography and radiography in 84 patients (67.2%). A single nucleus was present in 24 patients (19.2%) on sonography and 22 patients (17.6%) on radiography; it corresponded to the femoral center in all patients. The concordance between ultrasonography and radiography was 99% and 100%, respectively, for the detection of the femoral and tibial centers. Interobserver agreement was substantial to almost perfect for both ultrasonography and radiography. Ultrasonography is as effective as radiography in detecting knee ossification centers in PCH. It can be performed at the same time as thyroid examination, in place of radiography.