Congenital Hypothyroidism Children Research Articles

Molecular investigation of TSHR gene in Bangladeshi congenital hypothyroid patients.

The disorder of thyroid gland development or thyroid dysgenesis accounts for 80-85% of congenital hypothyroidism (CH) cases. Mutations in the TSHR gene are mostly associated with thyroid dysgenesis, and prevent or disrupt normal development of the gland. There is limited data available on the genetic spectrum of congenital hypothyroid children in Bangladesh. Thus, an understanding of the molecular aetiology of thyroid dysgenesis is a prerequisite. The aim of the study was to investigate the effect of mutations in the TSHR gene on the small molecule thyrogenic drug-binding site of the protein. We identified two nonsynonymous mutations (p.Ser508Leu, p.Glu727Asp) in the exon 10 of the TSHR gene in 21 patients with dysgenesis by sequencing-based analysis. Later, the TSHR368-764 protein was modeled by the I-TASSER server for wild-type and mutant structures. The model proteins were targeted by thyrogenic drugs, MS437 and MS438 to perceive the effect of mutations. The damaging effect in drug-protein complexes of mutants was explored by molecular docking and molecular dynamics simulations. The binding affinity of wild-type protein was much higher than the mutant cases for both of the drug ligands (MS437 and MS438). Molecular dynamics simulates the dynamic behavior of wild-type and mutant complexes. MS437-TSHR368-764MT2 and MS438-TSHR368-764MT1 showed stable conformations in biological environments. Finally, Principle Component Analysis revealed structural and energy profile discrepancies. TSHR368-764MT1 exhibited much more variations than TSHR368-764WT and TSHR368-764MT2, emphasizing a more damaging pattern in TSHR368-764MT1. This genetic study might be helpful to explore the mutational impact on drug binding sites of TSHR protein which is important for future drug design and selection for the treatment of congenital hypothyroid children with dysgenesis.

Neonatal screening for congenital hypothyroidism in Sweden 1980-2013: effects of lowering the thyroid-stimulating hormone threshold.

This study aims to evaluate the neonatal screening for congenital hypothyroidism (CH) and the diagnosis CH in the national health registers and to study the effects of lowering screening thyroid-stimulating hormone (TSH) threshold on the incidence of CH and birth characteristics of screening positive and negative CH children. This is a nationwide register-study of all children (n = 3 427 240) in the Swedish Medical Birth Register (MBR) and national cohort for screening positive infants (n = 1577) in 1980-2013. The study population was further linked to several other Swedish health registers. Evaluation of the CH screening and CH diagnosis was performed with levothyroxine use in the first year of life as reference. The incidence of CH was estimated by the Clopper-Pearson method. Regression models were used to study associations between CH and birth characteristics. The neonatal CH screening had high efficacy, but 50% of all children with a CH diagnosis were screening negative. The incidence of screening positive CH increased (1/3375 to 1/2222), and the incidence of screening negative CH decreased (1/2563 to 1/7841) after lowering the TSH screening threshold in 2009. Screening negative CH was associated with female sex, twinning, prematurity, low birth weight, birth defects, and need of neonatal intensive care, and 42% had transient disease. Despite high efficacy of the CH screening, 50% of children diagnosed as CH was screening negative. Although other factors influencing the incidence of the CH diagnosis cannot be ruled out, the incidence of screening negative CH decreased with lowering of the TSH threshold. Birth characteristics differed between screening positive and negative CH.

Genetic mutation profiles for children with congenital hypothyroidism in Fujian province

Objective: To explore the mutation characteristics of pathogenic genes in children with congenital hypothyroidism (CH) in Fujian. Methods: The clinical data of 116 unrelated CH children diagnosed in Fujian Provincial Maternal and Child Health Hospital from January 2019 to September 2020 were retrospectively analyzed, including 50 females and 66 males, with an average age of (20±10) days at diagnosis. Targeted exome sequencing technology was used to detect the mutation frequency, type and distribution characteristics of 29 genes related to thyroxine synthesis or thyroid development. Results: Three hundred and fifty-one potential functional mutations were detected in 105 of 116 CH patients, with a detection rate of 90.5% (105/116). DUOX2 (66.4%, 77/116) was the most frequent mutated gene, followed by TG (23.3%, 27/116), DUOXA1 (23.3%, 27/116), and TPO (12.1%, 14/116), which were all involved in thyroid hormone synthesis. Among the 105 children with CH, 70 cases carried double allele mutation. Except for 3 cases of thyroid dysplasia related genes (2 cases of TSHR and 1 case of GLIS3), the rest were also related to thyroid hormone synthesis. The gene with the highest carrier rate was DUOX2 (68.8%, 59/70), followed by TG (8.6%, 6/70), TPO (4.3%, 3/70), DUOXA2 (1.4%, 1/70) and DUOXA1 (1.4%, 1/70). Conclusion: The main mutated genes in CH children in Fujian are the key genes involved in thyroid hormone synthesis, such as DUOX2, TG and TPO.

Physical Development at School Entry in Children with Congenital Hypothyroidism Diagnosed by the National Program of Newborn Screening in Iran.

The newborn screening program for diagnosing and treating children with congenital hypothyroidism (CH) in Iran was established in 2004. This study aimed to evaluate the national program's success in maintaining the physical development and anthropometric indexes of children with CH. This historical cohort study was carried out in five provinces located in five different geographical regions of Iran. The anthropometric indexes, including weight, height, and head circumference of 240 children diagnosed with transient congenital hypothyroidism (TCH) (n = 131) and permanent congenital hypothyroidism (PCH) (n = 109) were measured and compared with those of 240 healthy children aged six. Mean ± standard deviation (SD) of weight, height, and head circumference of children with CH aged six were 20304.8 ± 4457.9 g, 115.6 ± 5.9 cm, and 50.8 ± 1.7 cm, respectively. Mean ± SD of height (116.7 ± 6.1 cm) and head circumference (51.1 ± 1.7 cm) in the control (healthy) group were significantly higher than those of the CH children group (P < 0.05). Mean ± SD weight in the control group (20741.2 ± 4337.3 g) was higher than that in the CH group (20304.8 ± 4457.9 g). However, the difference was not statistically significant (P = 0.3). No significant difference was observed between TCH and PCH children in the subgroup analysis (P > 0.05). Although the mean of anthropometric indexes in CH patients was slightly lower than that in healthy children aged six, the difference between the two groups was insignificant. The physical development of children with CH was evaluated as good. Our results suggested that the newborn screening program for identifying and treating children with CH in Iran may have improved the growth outcomes.

ODP459 Adiposity Rebound in Japanese Patients with Congenital Hypothyroidism Detected by Neonatal Screening

Abstract Background More than 40 years have passed since the introduction of newborn screening programs (NBS) for congenital hypothyroidism (CH), and there have been many reports on the long-term outcome of CH identified by NBS. There are some reports that CH is associated with early adiposity rebound and adult obesity. On the other hand, the association between AR and CH has not been revealed in Japan. Objective The aim of this study was to evaluate the timing of AR in individuals with CH detected by NBS in our institution, furthermore, to find out the risk factors of early AR in CH individuals. Patients and Methods The study included 212 CH children (105 female/107 males) who were ten years of age or older as of September 2021. We retrospectively collected height and weight data from one to ten years of age, and the timing of AR was visually determined. We examined the association between the AR age and the severity of hypothyroidism at NBS and at the first visit. Results The median AR age was 5.6 years for boys and 6.2 years for girls, which was unexpectedly not unexpectedly younger than that of the general Japanese population reported by Koyama (4.8 ± 1.4 years for boys, 4.7 ± 1.5 years for girls). Data from 115 patients (107 males, 105 females) whose physique data between the age of 15 and 18 were available showed that body mass index (BMI) was 21.1±3.2 kg/m2 for males and 20.6±2.7 kg/m2 for females, positively correlated with AR age, and not significantly different from BMI at 15-19 years of age (21.1±3.6 for males and 20.2±2.2 for females) in the 2019 National Nutrition and Health Survey (p=0.790, p=0.619). NBS-FT4 was slightly positively correlated to AR age (r=0.234, p=0. 0315). We found that the AR age may be earlier and adult BMI may be higher in CH patients without ossification of the distal femoral epiphyseal nucleus at first evaluation. Discussion Severe fetal hypothyroidism may cause an absence of mineralization of the distal femoral epiphyses in the neonatal period. Our results indicate that severe fetal hypothyroidism, even if diagnosed and treated at neonatal, contributes to the development of adult obesity. Conclusion The AR age and BMI at 15-18 years of CH are not significantly different from the general population. However, severe fetal hypothyroidism could result in adult obesity. Presentation: No date and time listed

Serological Characteristics, Etiological Analysis, and Treatment Prognosis of Children with Congenital Hypothyroidism.

Objective The aim of the study is to analyze the serological features, etiology, and prognosis of congenital hypothyroidism (CH) treated with L-thyroxine sodium (L-T4). Methods A total of 126 CH children in our hospital from June 2015 to January 2020 were selected as the research objects, and L-T4 treatment was given immediately after diagnosis. After diagnosis and 24 months of treatment, laboratory serum thyroid function-related indicators were examined, and thyroid changes were determined by ultrasound. We compared serum thyroxine levels in children with different thyroid changes, compared serum thyroid hormone levels, serum ghrelin levels, and body mass index (BMI) changes in children with CH before treatment and after 24 months of treatment, and analyzed the prognosis of treatment in children. In terms of thyroid changes in 126 CH children, 32 cases (25.40%) had a normal thyroid gland, 16 cases (12.70%) had a hypoplastic thyroid gland, 40 cases (31.75%) had an ectopic thyroid gland, 28 cases (22.22%) had an absent thyroid gland, and 10 cases (7.93%) had an enlarged thyroid gland, with an ectopic thyroid gland being the most common. In terms of serological expression of CH children, the TSH level in children with thyroid dysplasia was significantly higher than that in children with basic normal and T3 and T4 levels were significantly lower than those in children with basic normal (P < 0.05). At the same time, the TSH level in children with thyroid absence, ectopic, and enlargement was increased, while thyroxine (T4) and tri-iodothyronine (T3) levels were decreased compared with those in children with thyroid dysplasia. The difference was statistically significant (P < 0.05). Univariate analysis showed that there were statistically significant differences in birth weight, week of gestation at delivery, maternal age at childbirth, household registration, and a family history of thyroid disease compared between the two groups (P < 0.05); multivariate logistic regression analysis showed that birth weight <2,500 g, maternal age >35 years, rural residence, and a family history of thyroid disease were risk factors for neonatal CH (P < 0.05). Serum thyroid-stimulating hormone (TSH) levels, serum ghrelin levels, and the body mass index of children with CH decreased significantly, and T4 levels increased significantly after 24 months of treatment (P < 0.05). Conclusion Screening for common causes of CH is conducive to timely detection of children with CH, and L-T4 treatment can effectively improve thyroid function in children.

The effect of receiving thyroid hormone replacement on the dysphonia severity index for congenital hypothyroid children

ObjectivesDysphonia is a common compliant in hypothyroid patients. Subjective voice changes could be clearly found in congenital hypothyroid children (CHC); however, the early treated children with thyroid hormone replacement (THR) may not experience dysphonia. The objective of this study is to determine if the CHC who were receiving early THR would have objectively measurable changes on vocal function as assessed by the dysphonia severity index (DSI).MethodsParticipants were 29 children aged from 6 to 12 years. Fifteen children had congenital hypothyroidism on eltroxin therapy started before the age of 1 year and 14 were typically developing children (TDC). All children did not have voice compliant. DSI was calculated for all children through the measure of maximum phonation time (MPT), highest frequency (F0-high), lowest intensity (I-low), and jitter percent (j %).ResultsCHC receiving early THR were not significantly different from TDC on DSI value; however, both groups showed significant difference on MPT and F0-high. Degree of voice changes by DSI in males was significantly higher than females in CHC on eltroxin therapy while no significant difference regarding gender has been found on DSI in TDC.ConclusionsThe results suggested that there is no evidence of DSI objective voice changes in CHC receiving THR compared to TDC, yet separate objective voice measures alternations had been found in CHC. This highlights the importance of achieving efficient neonatal screening programs for CHC and providing strong support to initiate early THR to avoid any alternation of laryngeal function.

Evaluation of Hearing Loss in Congenital Hypothyroid Children at a Tertiary Care Hospital in Central India.

Hearing loss has long been associated with congenital hypothyroidism and, if not noticed and treated early, may result in delayed language acquisition and difficulties in comprehension. In light of the implications of congenital hypothyroidism and its associated hearing loss, we decided to conduct this study. The aim of this study was to identify the prevalence of hearing loss in congenital hypothyroidism and its relation to the severity of the disease and age of initiation of treatment. This study was conducted from July 2016 to June 2021 at a tertiary care hospital in Bhopal. The hearing status of congenital hypothyroid children and matched controls was assessed by pure tone audiometry or free field audiometry and, in selected cases, with brainstem evoked response audiometry. Eight children (25%) with congenital hypothyroidism had hearing loss, compared to one (3.12%) in the control group (p < 0.05). No statistically significant difference has been found in the gender, mean age of diagnosis, mean age of initiation of levothyroxine treatment, mean screening FT4 levels, and mean screening TSH levels between congenital hypothyroid children with and without hearing loss. Due to the high prevalence of hearing loss in congenital hypothyroidism and its impact on language and cognitive development, it is critical to create awareness among healthcare professionals that children diagnosed with congenital hypothyroidism must undergo audiological evaluation at the time of diagnosis and periodically thereafter. Alternatively, children with unexplained hearing loss must be screened for congenital hypothyroidism.

Comparison of Intelligence Quotient between Permanent Congenital Hypothyroid Children and Healthy Children

Background: Congenital hypothyroidism (CH) is the most common curable cause of mental retardation. The aim of this study was to compare the intelligence quotient (IQ) of congenital hypothyroid patients with healthy children. Methods: This two-group cross-sectional study was performed on 30 permanent CH children within the age range of 6-12 years referring to the Endocrine Clinic of Imam Reza Hospital, Mashhad, Iran between April 2017-2019. In addition, 32 healthy children of the same age and gender from the family members of the patients were chosen as the control group. The intelligence test was performed using the revised version of the Wechsler Intelligence Scale for Children and The mean verbal, performance, and total IQ was compared between case and control groups. Results: There was no significant difference between two groups in terms of age and gender. The mean verbal, performance, and total IQ in the case group were obtained as 104.33±13.30, 93.13±7.42, and 98.03±7.94, respectively. With regard to the healthy group, these mean values were respectively estimated at 121.34±16.74, 99.65±11.92, and 110.71±14.15 (the normal range of IQ was 90-109). Accordingly, the results revealed a significant difference between the two groups in terms of verbal (P=0.000), performance (P=0.013), and total (P=0.000) IQ. Furthermore, a relationship was found between early treatment initiation and higher verbal IQ (r=0.521; P=0.032), as well as between lower thyroid-stimulating hormone and higher performance IQ (r=0.559; P=0.020). Conclusion: The permanent CH children that had received timely treatment had normal levels of IQ based on the Wechsler Intelligence test. However, it was significantly lower in the CH children than that in healthy children of the same age, gender, and socioeconomic status.

Intelligence Quotient, Anxiety, and Depression in Congenital Hypothyroid Children at School Age.

Background:Many studies who evaluated the outcome of the congenital hypothyroidism (CH) screening reported some intellectual and behavioral deficit despite early diagnose and treatment. The aim of the present study was to compare the intellectual and behavioral adjustment of CH children with controls.Methods:This study was conducted among a group of 135 children aged 8--12 years in Isfahan, including transient and permanent congenital hypothyroidism (TCH and PCH) and a matched group of their classmate. Demographic characteristics collected using a designed data collecting form completed by parents. Intellectual quotient (IQ) was evaluated using Wechsler Intelligence Scale for Children aged 6--16 years (WISC-III). Depression and anxiety were evaluated using The Children's Depression Inventory (CDI) and the Multidimensional Anxiety Scale for Children (MASC), respectively. The SPSS software version 20.0 was used for data analysis. Nonparametric tests (Mann--Whitney) were used to investigate the association between variables. A significant level of less than 0.05 was considered in all analyzes.Results:There was no significant difference in the IQ scores between PCH and TCH groups (P = NS). However, neither of them had intellectual disability (defined as IQ <70). IQ scores were significantly lower in PCH comparing to controls (P < 0.001). Total IQ and verbal IQ were significantly differenct between TCH and control group (P = 0.007 and P = 0.001). No significant difference was found in anxiety and depression scores between CH children and controls.Conclusions:There is no significant difference in anxiety and depression scores between congenital hypothyroidism children and controls, although IQ scores in children with congenital hypothyroidism is lower than controls.

The characteristics of epidemiology, clinical and paraclinical manifestation of congetial hypothyroidism at Vietnam National Children’s Hospital

Objectives: To describe clinical and subclinical characteristics of congenital hypothyroidism children in Vietnam National childrens's hospital. Subjects: 52 children diagnosed with Congenital hypothyroisism and treatment at Vietnam National childrens's hospital from 01/2015 to 01/2020. Method: Retrospective description.. Results and conclussion: Most Congenital hypothyroidism infants could be detected early before 3 years, even in the newborn age. The suspected sign was constipation accompanied by edema, prolonged jaundice and mental retardation.&#x0D;

Comparison of Intelligence Quotient in Early Treated Neonates with Congenital Hypothyroidism Compared to Healthy Children

Background: Congenital hypothyroidism (CH) is one of the preventable causes of intellectual disability. The aim of this study was to compare intelligence quotient (IQ) in early treated children with CH and healthy children. Materials and Methods: This cohort study was conducted on 78 early treated children with CH (patient group) identified in screening program in Qazvin, Iran, started in 2006 and 90 age and sex matched healthy children (control group). The Persian version of Wechsler scale was performed to assess IQ (full scale, verbal, performance). Full-scale score among 70 and 80 were defined as borderline IQ and score among 50 and 69 were defined as mild mental retardation. Data were analyzed using SPSS software version 16.0. Results: Mean age was 6.57±1.92 in patients group and 6.94±1.57 in control group (P>0.05). 46/78 of the patient group and 51/90 of the control group were male (P>0.05). Mean full scale (87.01±13.47 vs. 107.45±10.49; P< 0.001), verbal (85.73±13.54 vs. 106.86±10.18; P< 0.001), and performance (89.44±13.66 vs. 110.62±9.82; P< 0.001) IQ in the patients group were significantly lower than the control group. 73.1% of the patients group had average and above IQ. Borderline IQ (14.1% vs. 0) and mild mental retardation (12.8% vs. 1.1%, P<0.001) in the patients group were significantly higher than the control group (P<0.001). Conclusion: Based on the results, although mean IQ in treated children with congenital hypothyroidism was lower than the control group, 73.1% of them had normal IQ. Early diagnosis and treatment of congenital hypothyroidism with high doses of thyroid hormone as well as patients' compliance can prevent mental retardation.

TUBB1 mutation in children with congenital hypothyroidism and thyroid dysgenesis in Shandong, China

To study the types and characteristics of TUBB1 mutation in children with congenital hypothyroidism (CH) and thyroid dysgenesis (TD) in Shandong, China. Mutations of the whole coding region of the TUBB1 gene were analyzed for 289 children with CH and TD in Shandong. Whole-genome DNA was extracted from peripheral blood leukocytes. PCR multiplication was performed for the whole coding region of the TUBB1 gene. Sanger sequencing was performed for the PCR products, and a biological information analysis was performed. Among the 289 children with CH and TD, 4 (1.4%) were found to have a c.952C>T(p.R318W) heterozygous mutation in the TUBB1 gene, resulting in the change of tryptophan into arginine at codon 318 of TUBB1 protein. This mutation was evaluated as "potentially pathogenic" based on the classification criteria and guidelines for genetic variation by American College of Medical Genetics and Genomics. A novel mutation is detected in the exon of the TUBB1 gene in children with CH and TD in Shandong, suggesting that the TUBB1 gene may be a candidate pathogenic gene for CH children with TD.

Developmental Outcomes in Early-treated Congenital Hypothyroidism: Specific Concern in Tc99m Thyroid Scan Role

Background Congenital hypothyroidism (CH) may cause alterations in the child's global development. The current study aimed to screen the global development of children with and without congenital hypothyroidism, focusing on communication, and cognitive abilities and to investigate the influence of illness severity, clinical history, and treatment factors in the evaluated results. Materials and Methods A case control study was conducted on 20 children with early-treated congenital hypothyroidism (CH), and controls without CH (n=100), both groups were matched for age and sex. Patients were subjected to a protocol of assessment applied in Pediatric and Phoniatrics Unit Sohag, Egypt. Assessments included detailed history and medical data, language development testing, intelligence quotient (IQ). According to TSH and T4 levels, case group was divided into controlled group and uncontrolled group. 99m pertechnetate scintigraphy of thyroid (Tc-99m TS) was recommended for all CH children. Results Children’s ages ranged between 3-7 years with a mean age of (4.6 ±1.9year). There were statistically significant differences between study and control group in presence of middle ear effusion, delayed language development, IQ scores (p<0.001). Interestingly, there was a negative correlation between IQ test and total language age with TSH level (r = -0.06, p= 0.004; r =-0.4, p=0.06), respectively. Tc-99m pertechnetate scintigraphy of thyroid confirmed transient CH diagnosis in three cases. Conclusion Despite early treatment in the studied CH children, language and cognitive skills impairments were detected. The magnitude of these impairments significantly related to TSH values and regularity of hormone replacement therapy. TS confirmed transient CH diagnosis in three cases, replacement therapy stopped in those children.

Analysis of DUOX2 mutations and inheritance pattern in Chinese patients with congenital hypothyroidism

Objective To investigate the prevalence of DUOX2 mutations in Chinese patients with congenital hypothyroidism (CH) and to discuss the inheritance pattern of DUOX2 gene. Methods Blood samples were collected from 91 CH children and their genomic DNA was extracted from peripheral blood leukocytes. All exons and exon-intron boundaries of DUOX2 were analyzed by target next-generation sequencing and family trios was established to study the inheritance pattern of DUOX2 gene. Results Fifty-four out of 91 children with CH carried DUOX2 mutation, with a prevalence of 59.34%. Of the 54 CH children, 36 carried DUOX2 biallelic mutations. In all 12 family trios with probands carrying biallelic DUOX2 mutations, the parents carried heterozygous DUOX2 mutations while still showing normal thyroid function, suggesting that CH caused by DUOX2 mutations is inherited in an autosomal recessive manner. Conclusion DUOX2 gene is one of the most frequently mutated genes in Chinese CH patients and its inheritance pattern is an autosomal recessive one. (Chin J Endocrinol Metab, 2017, 33: 567-573) Key words: Congenital hypothyroidism; Dualoxidase 2; Mutations; Recessive inheritance

Clinico-aetiological Profile of Congenital Hypothyroidism

Introduction: Thyroid hormone is critical for normal brain development in the early postnatal months. Biochemical diagnosis must be made soon after birth and effective treatment must be initiated promptly to prevent irreversible brain damage. Early diagnosis and adequate treatment from the first weeks of life result in normal linear growth and development. This study was conducted to find out the clinical features suggestive of congenital hypothyroidism and also its causation. Materials and Methods: This was a hospital based retrospective study of 40 congenital hypothyroid children conducted at endocrine unit of Kanti Children’s hospital from 2067 to 2072. All congenital hypothyroid children were reviewed in detail and frequency of signs/symptoms was calculated and also the possible causes were established using ultrasonography and scintigraphy.Results: Out of 40 congenital hypothyroid children 55% were male and 45% were female with M: F ratio of 1.23:1.Common age of presentation of congenital hypothyroidism was 6 to 12 months. The most frequent symptoms were decreased activity/ lethargy (78.9%) followed by stunted height (68.4%) and hypotonia (65.8%).Technetium thyroid scan was performed in 19 cases among which thyroid agenesis was the most common cause of congenital hypothyroidism (42.1%) followed by dyshormonogenesis (31.6%) and ectopic thyroid (26.3%).Conclusion: Early diagnosis of congenital hypothyroidism is possible in some children based on clinical features followed by biomedical investigation soon after birth.J Nepal Paediatr Soc 2016; 36(2):126-130

Five-Year Follow Up of Physical Growth and Thyroid Hormone Levels in Infants With Congenital Hypothyroidism

Background: Congenital hypothyroidism (CH) is one of the major causes of physical and mental disabilities, which are preventable and treatable. This study aimed to investigate physical growth and to evaluate the effectiveness of performed therapeutic interventions on normality of serum T4 and TSH levels in children with CH of Yazd city. Methods: This retrospective cohort study was performed on all neonates with CH, who were born during years 2006 and 2008. The growth pattern of height, weight and head circumference during the first five years of children with CH and the effectiveness of performed therapeutic interventions on normality of serum T4 and TSH levels were evaluated. The collected data were analyzed using the 22nd version of the SPSS software. Results: The pattern of height, weight, and head circumference of the girls with CH was comparable with the growth pattern of NCHS of healthy individuals. The pattern of height and weight growth of boys with CH gradually became similar to the growth pattern of NCHS of healthy boys. However, there was a decline in their head circumference growth trend after six months of age. Also it was revealed that therapeutic interventions had an appropriate effect on normalization of serum TSH, T4 levels and growth pattern in CH children under treatment. Conclusions: After treatment and care for these patients, the growth patterns and serum T4 and TSH levels of these children reached a normal and desirable range. Keywords: Congenital Hypothyroidism; Growth; Height; Weight; Head Circumference; Yazd

Frequency of thyroid status monitoring in the first year of life and predictors for more frequent monitoring in infants with congenital hypothyroidism.

The essential role of thyroid hormones for normal brain development during a critical period of life is well established. Neonatal screening programs for congenital hypothyroidism (CH) enable early detection of patients and attainment of euthyroid status as quickly as possible. Adequate and accurate monitoring of thyroid function is necessary. In the study we aimed to determine the periodicity of thyroid function testing in the first year of life (3-month intervals versus <3-month intervals monitoring). We retrospectively analyzed charts of CH children from Macedonia detected on neonatal screening during a 3-year period (2011-2014). Needs for monthly thyroid monitoring were defined according to the recommendations: a dose change within a month of a previous control, values of T4/FT4 not in the upper half of the reference range, and a high or very low thyroid-stimulating hormone (TSH) value. Monthly thyroid testing was indicated in more than a third of CH patients during the first year of life. Children who needed more frequent monitoring intervals had a higher initial value of TSH (p=0.032) and a lower value of T4 (p=0.038) than those requiring less frequent monitoring. The sex, birth weight, age of treatment onset, initial L-thyroxine dose, and L-thyroxine dose at 1-year of age in our study were not predictive factors for more frequent thyroid monitoring. Children with severe hypothyroidism at birth are potential candidates for more frequent thyroid monitoring during the first year of life, although the individual patient approach should not be avoided as variations in TSH values are very common.

Cognitive outcomes for congenital hypothyroid and healthy children: a comparative study.

Early diagnosis and treatment of congenital hypothyroidism (CH) and the prevention of developmental retardation is the main goal of public health national screening programs. This study compares the cognitive ability of children with CH diagnosed by neonatal screening with a healthy control group (2007) in Yazd, Iran. In a case-controlled study, the intelligent quotient (IQ) of 40 five-year-old children with early treated CH and good compliance were evaluated by the Wechsler preschool and primary scale of intelligent test and compared to 40 healthy age and gender matched children as controls. 22 boys (55%) and 18 girls (45%) in both groups were evaluated. In children with CH, 19 (47.5%) and 21 (52.5%) persons had transient and permanent hypothyroidism, respectively. Range of TSH and T4 level at the onset of diagnosis were 11.41-81 mu/l and 1.50-14.20 μg/dl, respectively. The intelligence levels of all children with CH were within the average or normal range and IQs ranged from 91-108. Children with CH had lower full-scale IQs (107.25 ± 2. 9 versus 110.50 ± 2.66, p=0.001), verbal IQ (106.95 ± 3.5 versus 109.90 ± 3.44, P-value=0.001) and performance IQ (106.3 ± 3.68 versus 108.87 ± 3.70) than the control group. However, no statistically significant differences were observed for mean IQ scores in permanent and transient CH. Children with CH who had early treatment and good compliance had normal cognitive abilities, but may have a decreased IQ relative to the healthy control group.

Neurodevelopmental outcomes are normal in congenital hypothyroid children diagnosed early and treated aggressively over the first three years

Despite marked improvements in developmental outcome with newborn screening and early levothyroxine replacement most follow up studies of congenital hypothyroidism (CH) show a persistent mild deficit in total IQ. It has been considered that these deficits in neurocognitive function occur in utero and thus even early therapy cannot completely normalise development. Alternatively the deficits could be caused by delayed diagnosis and inadequate early treatment. In Auckland, early diagnosis occurs via our newborn screening programme along with an aggressive high dose treatment paradigm following referral to the endocrine service. Thus we hypothesised that early diagnosis and aggressive therapy with close monitoring would result in normal neurocognitive outcomes.