Congenital Hypothyroidism Group Research Articles

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 an increased identification of newborns with transient CH. Several studies 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 to 2018 at the Pediatric Endocrine Institute of Ha'Emek Medical Center were enrolled in the study. Data were retrieved retrospectively from medical files. Included in the study were 76 newborns (45M,59%) with transient CH and 53 (25M,47%) with permanent CH. The major cause of transient CH was prematurity (29%) and subclinical hypothyroidism (30%). During retrospective follow-ups of up to 23 years, reinitiation of LT4 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 limited to infancy. SCH frequently presents as overt hypothyroidism at birth but in most cases the requirement for LT4 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.

Incidence and associated risk factors of congenital hypothyroidism among newborns in Hainan, China: a retrospective study.

This study aims to investigate the incidence and risk factors of congenital hypothyroidism (CH) in newborns in Hainan Province, China, to provide a reference for early and effective prevention strategies. Newborns born in Hainan Province from 2017 to 2021 were the subjects of this study. Time-resolved immunofluorescence was used for initial screening and chemiluminescence for confirmatory diagnosis. Based on the diagnosis, newborns were classified into CH and non-CH groups. Statistical analysis was conducted on the initial screening and confirmed CH cases in newborns in Hainan Province, and potential risk factors for CH were explored. From 2017 to 2021, a total of 585,886 newborns were screened, revealing 6,856 initial positive results, 614 positive rescreens, and 420 confirmed CH cases, yielding an incidence rate of 1/1,395 (420/585,886). The annual initial positive screening rate of newborns in Hainan Province showed a rising trend from 2017 to 2021 (p=0.000). No significant differences were found regarding gender (p=0.400) and ethnicity (p=0.836). Multivariate logistic regression analysis indicated that residing in coastal areas, especially those with salt fields (OR=2.151, 95 % CI: 1.364-3.390), was risk factors for the development of CH in newborns. The incidence of CH in newborns showed a year-on-year increase in Hainan Province from 2017 to 2021. Residing in coastal areas, particularly those with salt fields, was identified as a risk factor for the development of CH.

Intelligence quotient (IQ) outcome in children with early-treated congenital hypothyroidism: a systematic review and meta-analysis

Background Congenital hypothyroidism (CH) is the most common congenital endocrine disorder in childhood and is one of the most preventable causes of intellectual disability (ID). Late initiation of thyroid hormone substitution therapy has a negative impact on intellectual abilities in CH patients.
 Objective To compare Intelligence Quotient (IQ) between children with CH who underwent early treatment among the children without CH.
 Methods We performed online literature searches of ScienceDirect, Pubmed, Cochrane Library, and Google Scholar. We included clinical studies that examined IQ scores in patients with early-treated CH and without CH. Review Manager 5.4 was used to perform the meta-analysis.
 Results Twelve studies comparing pediatric patients with and without CH were included in this meta-analysis, for a total of 808 patients. Based on data analysis, IQ levels of verbal IQ [mean difference (MD) -9.05; (95%CI -14.51 to -3.59); (P<0.00001)], performance IQ [MD -11.70; (95%CI -17.41 to -5.99); (P<0.00001)], and total IQ [MD -10.78; (95%CI -14.03 to -7.54); (P<0.00001)]. While verbal, performance, total, of the early-treated CH group were within the normal range, they were each significantly lower than those in the non-CH group.
 Conclusion This meta-analysis reveals that IQ scores in early-treated CH subjects were within normal limits, but significantly lower than that of normal controls.

The impact of subclinical hypothyroidism on growth and development in infants and young children aged 0 to 5 years.

The objective was to investigate the growth and development of infants and young children with mild subclinical hypothyroidism aged 0 to 5 years, especially those aged 0 to 2 years. The study was a retrospective analysis of the birth status, physical growth, and neuromotor development of patients aged 0 to 5 years, who were diagnosed with subclinical hypothyroidism during newborn screening (NBS) in Zhongshan between 2016 and 2019. Based on preliminary results, we compared 3 groups: with thyroid-stimulating factor (TSH) value of 5-10 mIU/L (442 cases), TSH value of 10-20 mIU/L (208 cases), and TSH above 20 mIU/L (77 cases). Patients with TSH value above 5 mIU/L were called back for repeat testing and were divided into 4 groups as follows: mild subclinical hypothyroidism group 1 with a TSH value of 5-10 mIU/L in both initial screening and repeat testing; mild subclinical hypothyroidism group 2 with TSH value above 10 mIU/L in initial screening; and TSH value of 5-10 mIU/L in repeat testing; the severe subclinical hypothyroidism group with TSH value of 10-20 mIU/L in both the initial screening and repeat testing and the congenital hypothyroidism group. There were no significant differences in the maternal age, type of delivery, gender, length, and weight at birth between the preliminary groups; however, the gestational age at birth was significantly different (F = 5.268, p = 0.005). The z-score for length at birth was lower in the congenital hypothyroidism group compared to the other 3 groups but showed no difference at 6 months of age. The z-score for length in mild subclinical hypothyroidism group 2 was lower compared to the other 3 groups but showed no difference at 2-5 years of age. At 2 years of age there was no significant difference in the developmental quotient (DQ) of the Gesell Developmental Scale between the groups. The gestational age at birth affected the neonatal TSH level. Intrauterine growth in infants with congenital hypothyroidism was retarded compared to that of infants with subclinical hypothyroidism. Neonates with a TSH value of 10-20 mIU/L in the initial screening and a TSH value of 5-10 mIU/L in the repeat testing showed developmental delay at 18 months but caught up at age 2 years. There was no difference in neuromotor development between the groups. Levothyroxine in patients with mild subclinical hypothyroidism is not required, but we recommend that the growth and development of such infants and young children continues to be monitored.

The length of FOXE1 polyalanine tract in congenital hypothyroidism: Evidence for a pathogenic role from familial, molecular and cohort studies.

FOXE1 is required for thyroid function and its homozygous mutations cause a rare syndromic form of congenital hypothyroidism (CH). FOXE1 has a polymorphic polyalanine tract whose involvement in thyroid pathology is controversial. Starting from genetic studies in a CH family, we explored the functional role and involvement of FOXE1 variations in a large CH population. We applied NGS screening to a large CH family and a cohort of 1752 individuals and validated these results by in silico modeling and in vitro experiments. A new heterozygous FOXE1 variant segregated with 14-Alanine tract homozygosity in 5 CH siblings with athyreosis. The p.L107V variant demonstrated to significantly reduce the FOXE1 transcriptional activity. The 14-Alanine-FOXE1 displayed altered subcellular localization and significantly impaired synergy with other transcription factors, when compared with the more common 16-Alanine-FOXE1. The CH group with thyroid dysgenesis was largely and significantly enriched with the 14-Alanine-FOXE1 homozygosity. We provide new evidence that disentangle the pathophysiological role of FOXE1 polyalanine tract, thereby significantly broadening the perspective on the role of FOXE1 in the complex pathogenesis of CH. FOXE1 should be therefore added to the group of polyalanine disease-associated transcription factors.

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.

ODP391 Neurodevelopmental and Growth Outcome of Congenital Hypothyroidism: A National Investigation of Birth Cohort Study

Abstract Objectives The purpose was to investigate the neurodevelopmental and growth status of Congenital hypothyroidism (CH) patients compared to normal children using population-based cohort study. Methods The National Investigation of Birth Cohort in Korea study 2008 (NICKs-2008) consisted of the Korean National Health Insurance System (NHIS) and the National Health Screening Program for Infants and Children (NHSPIC) databases comprising children born in 2008 (n=469,248) and 2009 (n=448,459). The CH patients were enrolled with International Classifications of Diseases-10 codes and drug classification (levothyroxine over 5 years) codes. We investigated their developmental outcomes using the Korean-Ages and Stages Questionnaire (K-ASQ), and serial changes of BMI (BMI-z) and height (height -z) were compared in children with and without CH. Risk ratios were obtained using a modified Poisson regression and weighted risk differences using binomial regression. Results Of the 919,707 newborns, 433 children (boys, 47.7%) were diagnosed as CH (1: 2,124 of prevalence). The risk ratio (RR) for delayed development based on the results from the 5th–7th K-ASQ was higher for the total developmental area (adjusted RR = 2.77, 95% CI: 1.507-5.118) in CH patients. There was significant difference between patients with CH and controls in the assessment of gross motor, fine motor and problem-solving areas (P &amp;lt; . 0001). At 66-71 months of age, short stature (height-z &amp;lt; -1.63) were increased in the CH group compared with normal children (adjusted RR 2.27, 95% CI 1.328-3.865). Obese children (BMI-z &amp;gt; 1.63) were not increased. Conclusions The adequate large cohort data showed that prevalence of developmental delay and short stature were higher in CH patients than normal. Careful and early intervention is needed. Presentation: No date and time listed

Psychosocial Impact of the COVID-19 Pandemic on Children with Congenital Adrenal Hyperplasia and Their Families.

This study aimed to investigate the psychosocial impact of the pandemic in pediatric patients with congenital adrenal hyperplasia and their families and whether congenital adrenal hyperplasia imposes an additional burden compared to other endocrine disorders. Patients with congenital adrenal hyperplasia (n = 38) and congenital hypothyroidism (n = 41) and their families were enrolled in the prospective longitudinal survey study. Questionnaires that were completed remotely in June 2020 and in July 2021 included Depression Anxiety Stress Scale short form, The State-Trait Anxiety Inventory for Children, and purpose-built daily routine, parent, and child COVID information scores, factors affecting drug usage, and parents' thoughts about the pandemic. At the end of 1 year, Depression Anxiety Stress Scale short form and State-Trait Anxiety Inventory for Children were repeated in the congenital adrenal hyperplasia group and they were questioned about the incidence and severity of coronavirus infection. Median Depression Anxiety Stress Scale short form and State-Trait Anxiety Inventory for Children scores were similar between the congenital adrenal hyperplasia and congenital hypothyroidism groups. In the congenital adrenal hyperplasia group, median purpose-built daily routine was higher in those who had a State-Trait Anxiety Inventory for Children-State score above the threshold (P = .048), also Depression Anxiety Stress Scale short form-Depression, Depression Anxiety Stress Scale short form-Anxiety, Depression Anxiety Stress Scale short form-Stress, Parent COVID Information Score were higher among parents who followed news/data because of chronic diseases/medications of the child (P = .010, P = .034, P = .044, P = .045, respectively), and State-Trait Anxiety Inventory for Children-State was higher among parents who believed "having chronic diseases" and "using medications" increase the risk of COVID-19 infection (P = .011, P = .016, respectively). In the second survey, State-Trait Anxiety Inventory for Children-State, Depression Anxiety Stress Scale short form-Anxiety, and Depression Anxiety Stress Scale short form-Stress decreased significantly (P < .01, P = .009, P = .008, respectively). Three patients with congenital adrenal hyperplasia who reported positive nasopharyngeal swab tests revealed mild symptoms. The pandemic has negative consequences on the mental well-being of individuals with chronic diseases, albeit from different causes.

Free triiodothyronine/free thyroxine ratio in children with congenital hypothyroidism.

Thyroid-stimulating hormone is generally regarded as a standard parameter for the evaluation of thyroid function. However, relying on this hormone alone can be misleading. Therefore, thyroxine/free-thyroxine levels are used in patients with levothyroxine substitution for the adjustment of therapy. Even with normal values for free thyroxine, decreased values for the free-triiodothyronine/free-thyroxine ratio have already been described in adults. In this study, the free-triiodothyronine/free-thyroxine ratio of 25 children with congenital hypothyroidism was compared with 470 healthy children seen for other reasons and then for thyroid dysfunction. Mean free thyroxine in congenital hypothyroidism was just below the upper limit of normal and significantly higher than in control group. Mean values for free triiodothyronine showed no significant difference between the two groups. The mean value for the free triiodothyronine/free-thyroxine ratio in control group was 3.23. Significantly lower ratios were found in the congenital hypothyroidism group with a mean value of 2.5, due to higher values for free thyroxine compared to free triiodothyronine. Furthermore, an increased free triiodothyronine/free-thyroxine ratio was found at higher thyroid-stimulating hormone values due to lower values for free thyroxine. In this study, we demonstrate that the free triiodothyronine/free-thyroxine ratio was significantly lower in children with congenital hypothyroidism compared to the control group. This is most likely due to the higher values for free thyroxine in this group compared to similar values for free triiodothyronine in both groups. Further studies with differentiated thyroid hormone therapy are needed in order to understand the role of peripheral euthyroidism.

Evaluation of permanent and transient congenital hypothyroidism in cases referred from National Neonatal Screening Program.

The incidence of congenital hypothyroidism (CH) has increased world-wide. Lowering cut-off in screening programs has led to an increase in the rate of transient CH. We aimed to evaluate the rates of permanent and transient CH in cases referred from the screening program and to investigate the clinical and laboratory factors which predict transient CH. In 109 cases referred from the neonatal screening program to our hospital, from September 2015 to April 2018, 52 primarily diagnosed CH cases were prospectively evaluated. Regularly followed up, 44 CH cases were included in the study at the end of 3 years. 38.2 ± 1.31 weeks (w) and mean birthweight 3021.3 ± 389.6gram (g) in the transient CH group; both were significantly lower compared to permanent CH cases with 39.06 ± 1.33 w and 3375.3 ± 425.3g (P=0.025, P=0.007) respectively. Transient CH rate was found to be 50% (all hypoplastic) in the dysgenesis group and 73.3% in groups with normal and hyperplasic thyroid gland. While fT4 , thyroid-stimulating hormone, and thyroglobulin levels at diagnosis do not predict transient/permanent CH, levothyroxine (LT-4) dosage was significantly lower in the transient CH group in all years. The optimal cut-off value with highest sensitivity and specificity for LT-4 dosage as a predictive marker to differentiate transient CH from permanent CH was 2.27μg/kg/day (P=0.004; sensitivity: 71%, specificity: 83%) at 1st year, 1.85μg /kg/day (P=0.013; sensitivity: 66%, specificity: 72%) at 2nd year and 1.69μg /kg/day at 3rd year (P < 0.0001; sensitivity: 90%, specificity: 83%). Transient CH is more frequent than expected. Our results suggest that LT-4 requirement may be a good marker for predicting transient CH, while thyroid hormone levels at the time of diagnosis do not significantly predict permanent and transient CH. Therefore, infants with CH requiring LT-4 doses <2.27 μg/kg/day at 1st year, <1.85 μg /kg/day at 2nd year may be re-evaluated earlier to discriminate transient CH rather than at 3 years of age.

Perinatal risk factors for congenital hypothyroidism in very preterm infants: a multicenter prospective study

Objective: To investigate the incidence and perinatal risk factors of congenital hypothyroidism (CH) in very preterm infants. Methods: This prospective, multicenter observational cohort study was conducted at 33 neonatal intensive care units based on the data from Sina-northern Neonatal Network (SNN). Perinatal information and thyroid function of 3 179 very preterm infants with gestational age <32 weeks who were born from January 2019 to June 2021 was collected. According to the occurrence of CH during hospitalization, all the infants were assigned into CH group and non-CH group. Chi square test, Fisher exact probability method, rank sum test and multivariate Logistic regression model were tested to detect the perinatal risk factors for CH. Results: A total of 3 179 very preterm infants were enrolled with 56.4% (1 793/3 179) male. The incidence of CH was 6.9% (220/3 179), in which the incidence for extremely low birth weight infant (ELBWI) and extremely preterm infants (EPI) of gestational age <28 weeks were 13.5% (64/475) and 13.9% (66/475), respectively. On Logistic regression analysis, maternal hypertensive disorders of pregnancy (OR=1.59, 95%CI 1.14-2.23, P=0.007) and multiple birth (OR=1.60, 95%CI 1.18-2.17, P=0.003) were both significant perinatal risk factors of CH. In addition, gestational age (OR=0.81, 95%CI 0.71-0.93, P=0.002), birth weight (OR=0.99, 95%CI: 0.98-0.99, P<0.001) and 1 min Apgar score (OR=0.92, 95%CI 0.86-0.98, P=0.008) were protective factors. Conclusions: The incidence of CH is high in very preterm infants which increased with the decreased birth weight and gestational age. For very premature infants with perinatal high risk factors such as hypertensive disorders of pregnancy, attention should be paid to assess thyroid function status dynamically.

Basal Serum Thyroxine Level should Guide Initial Thyroxine Replacement Dose in Neonates with Congenital Hypothyroidism

Objective:Initial high-dose sodium levothyroxine (Na-LT4) (10-15 μg/kg/day) replacement for primary congenital hypothyroidism (CH) is recommended in guidelines. However, high-dose Na-LT4 risks iatrogenic hyperthyroidism. The aim of this study was to investigate the normalizing effect of varying initial doses of Na-LT4 on serum thyroid hormone levels.Methods:Fifty-two patients were analyzed retrospectively. The patients were classified into mild (27/51.9%), moderate (11/21.1%) and severe (14/26.9%) CH, based on initial free thyroxine (fT4) levels. Time taken to achieve target hormone levels was compared within groups.Results:Initial mean Na-LT4 doses for mild, moderate and severe disease were 6.9±3.3, 9.4±2.2 and 10.2±2 μg/kg/day. Serum fT4 levels reached the upper half of normal range (>1.32 ng/dL) in a median of 16, 13 and 16 days in patients with mild, moderate and severe CH with the mean time from initial treatment to first control visit of 14.8±6 days (range 1-36). There was no significant difference in terms of time to achieve target fT4 hormone levels according to disease severity (p=0.478). Seven (25.9%), eight (72.7%) and eight (57.1%) patients experienced hyperthyroxinemia (serum fT4 >1.94 ng/dL) in the mild, moderate, and severe CH groups at the first visit, respectively (p=0.016).Conclusion:Not all patients diagnosed with CH require high-dose Na-LT4. Initial dose of Na-LT4 may be selected on the basis of pretreatment thyroid hormone levels. Some patients with moderate and severe CH, experienced iatrogenic hyperthyroxinemia even though the dose was close to the lower limit of the recommended range in guidelines. We suggest that lower initial doses may be appropriate with closer follow-up within the first week.

Our Newborn Hearing Screening Results of Infants with Congenital Hypothyroidism

Objective: We aimed to reveal newborn hearing screening test results and risk factors of babies diagnosed with congenital hypothyroidism (CH) in our hospital. Material and Methods: The files of the newborns who were evaluated within the scope of the national newborn screening program between January and December 2019 were retrospectively reviewed. Risk factors were evaluated by comparing newborn hearing screening test results of babies with CH and euthyroid control groups. Results: There was no significant difference between the two groups in terms of demographic and pregnancy datas. There was no significant difference between the CH and control groups in terms of the rate of failed/passed patients from the hearing screening tests. Patients with thyroid hypoplasia at CH group failed at a higher rate from the first hearing screening test. Conclusion: In this study, there was no significant difference between CH and control groups in terms of hearing screening results.

Necroptosis mediated by receptor interacting protein kinase 3 as critical players in experimental congenital hypothyroidism related neuronal damage.

OBJECTIVE:Congenital hypothyroidism (CH) is literally described as congenital thyroid hormone imperfection. The primary objective of this research was to reveal the possible relation between receptor-acting protein kinase 3 (RIPK3) activity and neuronal damages in rat pups with CH. In addition, we evaluated the favorable impacts of 3.6-dibromo-α-([phenylamino] methyl)-9H-carbazole-9-ethanol (P7C3) reducing RIPK3 activity.METHODS:Adult rats were accordingly assigned into four groups: Group 1, which is called congenital hypothyroid; Group 2, which is called congenital hypothyroid administered P7C3; Group 3, called CH administered P7C3 and L-thyroxine; and Group 4, control group. RIPK3 level in plasma concentration and its expression in tissue was determined in all groups.RESULTS:Increased RIPK3 expressions were detected as high in the CH group when it is compared to the control group. Furthermore; the expressions in neuronal cytoplasm were found similar among Groups II and III. RIPK3 expressions in those two groups were relatively higher than in the control group. Most reacted parts of the brain were especially Purkinje cells in the cerebellum.CONCLUSION:It is concluded that there is excellent parallelism among damaged neurons and high RIPK3 activity in CH pathogenesis. P7C3 compounds may have a safeguarding impact on CH due to decreasing RIPK3 activity.

Spectrum of clinical presentation of thyroid disorders in children in a tertiary care teaching hospital: An observational study

Introduction: Thyroid disorders during childhood are quite common and presentations are nonspecific. Congenital hypothyroidism (CH), among all causes of childhood hypothyroidism, is the most important, as early detection and appropriate therapy can prevent the onset of brain damage. The delay in diagnosis is attributable to the lack of awareness, lack of available facilities, or newborn screening programs. Aims: This study aims to study the spectrum of clinical presentation of thyroid disorders in children in a tertiary care teaching hospital. Materials and Methods: A descriptive observational study was conducted for a 2-year period, from January 2018 to January 2020. All children who were referred to the pediatric endocrine out-patients clinic for suspected thyroid dysfunction were included in this study. Data on patients history, clinical examination including the presence of goiter and laboratory tests were collected and analyzed. Results: Of 86 children with suspected thyroid dysfunction, 32 had abnormal thyroid function tests. Six had CH, 19 had overt acquired hypothyroidism and six had subclinical acquired hypothyroidism. Thyroid peroxidase antibodies were elevated in 13 children with no gender predilection. There was a female preponderance across all the age groups but no gender predilection was noted in the CH group. Short stature was noted in 70.9% of cases, diminution in school performance in 58% and pallor in 29%. Goiter was observed in 9.6% of children. Conclusions: In our study, 80.6% had acquired hypothyroidism. The most common presenting feature was short stature which was observed in 70.9% of our children. Diminution of scholastic performance was the second common clinical feature which was observed in 58% of children.

Konjenital Hipotiroidi Olgularının Etiyolojik Değerlendirilmesi

INTRODUCTION: The aim of this study was to determine, (i) the cause of congenital hypothyroidism (permanent or transient), (ii) the etiological cause of persistent congenital hypothyroidism and (iii) to investigate the role of clinical and laboratory data in predicting persistent and transient congenital hypothyroidism. METHODS: Patients with congenital hypothyroidism who were started L-thyroxine treatment and discontinued at the age of 3 years were included in the study. The data of the cases were obtained retrospectively from the hospital records. Serum thyroid hormones were measured of the cases 4 weeks after discontinuation of treatment at the age of 3 years. Patients with TSH&gt; 10 mIU/mL were accepted as permanent hypothyroidism and those with normal TSH value for 6 months were accepted as transient hypothyroidism. RESULTS: A total of 63 patients were included in the study. Permanent congenital hypothyroidism was detected in 16 (25%: 9 females, and 7 males) and transient congenital hypothyroidism in 47 (75%: 22 females, and 25 males) cases. There was no difference between the permanent and transient groups in terms of gender, gestational week, birth weight, age at diagnosis, physical examination findings at the time of diagnosis, serum fT4, TSH levels, and initial L-thyroxine doses. While thyroid ultrasonography was normal in all patients in the transient hypothyroidism group, dysgenesis was detected in 9 (56%), and dyshormonogenesis in 1 (6%) patient. The mean thyroxin dose in permanent congenital hypothyroidism group was significantly higher than the transient group at the time of treatment cessation (2.8±0.9 and 1.2±0.5 mcg/kg/day, p&lt;0.001, respectively). L-thyroxin dose of &gt;2.1 mcg/kg/d was 81% sensitive and 90% specific for predicting permanent congenital hypothyroidism (p&lt;0.001). DISCUSSION AND CONCLUSION: It has been shown that the most common etiologic cause of congenital hypothyroidism is transient hypothyroidism. Thyroxine dose at the time of treatment cessation was found to be the most important determinant in the differentiation of permanent and transient congenital hypothyroidism.

The relationship between nonalcoholic fatty liver disease and pediatric congenital hypothyroidism patients.

Previous studies have shown hypothyroidism was independently associated with nonalcoholic fatty liver disease (NAFLD) in adults, but few studies examined their relationships in pediatric populations. This study aimed to investigate the prevalence of NAFLD in pediatric congenital hypothyroidism (CHT) patients and to identify the association between CHT and NAFLD. This study enrolled pediatric CHT patients receiving levothyroxine treatment at one medical center from 2013 to 2014. Euthyroid subjects (ET) and transient hypothyroidism (THT) patients weaned off medication successfully after age 3 were selected for further comparison. Laboratory data including thyroid functions, liver functions, and metabolic profiles were obtained. The major outcome was the occurrence of NAFLD, diagnosed based on the findings of abdominal ultrasonography. One-hundred and twenty-nine subjects (47 in CHT, 47 in THT, and 35 in ET groups) were enrolled. The analysis showed higher fasting serum glucose, insulin, thyroxine (T4), and mean thyroid-stimulating hormone (TSH) levels in the CHT group. NAFLD prevalence was higher in the CHT (23.4%) group than in the THT (8.5%) and the ET (5.7%) groups, demonstrating an increasing trend across three strata (X2 linear-by-linear = 5.9, P < .05). The multivariate regression analysis showed obesity (β-coefficient = 5.52, P < .05), CHT (β-coefficient = 2.92, P < .05) and mean TSH levels (β-coefficient = 0.24, P < .05) were independent risk factors for NAFLD. A positive correlation was found between TSH level and lipid profiles. CHT patients had higher risk of NAFLD despite treatment being initiated early in life. Close monitoring of metabolic profiles is warranted. Further research should examine ways to optimize the treatment for CHT patients in terms of prevention against NAFLD.

Adrenal Steroids in Female Hypothyroid Neonates: Unraveling an Association Between Thyroid Hormones and Adrenal Remodeling.

The adrenal gland undergoes substantial remodeling during the neonatal period, an essential developmental process that remains incompletely understood. With respect to control over the remodeling process and, specifically, the role of thyroid hormones (THs), no human studies have been published. The effects of both hypo- and hyperthyroidism have only been evaluated in adults, focusing on the mature adrenal. Recent studies have identified expression of the TH receptor β1 in the mouse adrenal X-zone and have demonstrated that TH administration could alter the postnatal adrenal remodeling process. To address whether THs influence adrenal steroid profiles and adrenal remodeling during the neonatal period. We compared the adrenal steroid profile of a naturally occurring prototype, female neonates with severe congenital hypothyroidism (CH) (n = 22, upon diagnosis of CH), with that of euthyroid neonates (n = 20). Significantly higher levels of adrenal steroids (17-OH-progesterone, dehydroepiandrosterone sulfate, Δ4-androstenedione, and testosterone) were measured in neonates with severe CH compared with euthyroid neonates and returned to within normal range after euthyroid state had been established on l-thyroxine replacement therapy, whereas cortisol levels did not differ. TSH values in the CH group were positively correlated with circulating adrenal steroids, whereas free T4 levels were negatively correlated with circulating adrenal steroids. The hormonal profile of female neonates with severe CH suggests a more active adrenal fetal zone compared with control subjects. These data indirectly associate THs with the adrenal remodeling and maturation process in humans. Based on our results, we suggest that severe hypothyroidism decelerates the involution of the adrenal fetal zone that normally occurs postnatally.

White matter microstructural abnormalities in children with severe congenital hypothyroidism.

This study assessed white matter microstructural integrity and behavioral correlates for children with severe congenital hypothyroidism (CH) who were identified and treated early following newborn screening. Eighteen children with severe CH and 21 healthy controls underwent a battery of behavioral measures of hearing, language and communication, along with diffusion MR imaging. Tract-based spatial statistics were performed on standard diffusion parameters of fractional anisotropy and diffusivity metrics. Microscopic diffusion anisotropy mapping based on the Spherical Mean Technique was also used to evaluate biologically specific metrics. Compared with age-matched controls, children with severe CH had poorer hearing and communication skills, albeit generally within normal limits. Children with severe CH had fractional anisotropy that was significantly lower in the cerebellum, bilateral thalami and right temporal lobe, and radial diffusivity that was significantly higher in the cerebellum and bilateral thalami. Microscopic fractional anisotropy and intra-neurite volume fraction were also significantly decreased, and transverse microscopic diffusivity was significantly increased, in the CH group in areas including the cerebellum, thalamus, occipital lobe, and corpus callosum, and in the white matter adjacent to sensorimotor cortex, particularly in the left hemisphere. Significant and widespread correlations were observed between behavioral measures and measures of white matter microstructural integrity in children with CH. The results indicate that children with severe CH who are identified through newborn screening may have significant brain white matter microstructural abnormalities despite early treatment.

Cyclic alternating pattern in infants with congenital hypothyroidism

Congenital hypothyroidism is defined as thyroid hormone deficiency present at birth which is crucial for brain development. Recently, the cyclic alternating pattern, a rhythm present in electroencephalography recordings in non-Rapid eye movement sleep, has been related to brain development and cognition in different pediatric conditions. Therefore, we evaluated the cyclic alternating pattern rate in infants with congenital hypothyroidism, thyroxine supplementation, and healthy controls. The parameters of the cyclic alternating pattern were evaluated in 19 healthy infants (10 female, mean age 25.5 ± 15.5 months) and 21 infants diagnosed with congenital hypothyroidism (19 female, mean age 24.3 ± 19.0 months). We considered the transient electro-cortical activations (phase A of the cycle) in non-Rapid eye movement sleep and the subdivisions of the A phase in: A1, A2 and A3, based on their frequency content. All subjects were subjected to polysomnography recording in a standard laboratory setting. Sleep data were stored computer following the International 10–20 System. Data showed that congenital hypothyroidism infants exhibited higher frequency of central apnea, hypopnea, and arousals in comparison to controls. Particularly, central apnea index decreased with age in the control group but not in congenital hypothyroidism group. Regarding to cyclic alternating pattern measurements, congenital hypothyroidism infants exhibit a higher frequency in the percentage of A3 subtype (electroencephalographic desynchrony) and conversely a lower percentage of A1 subtype (electroencephalographic synchrony), than healthy infants. An important finding of this study is the positive correlation between A1 mean duration and age, which is bigger in control group than in congenital hypothyroidism group (time duration in control group (0.52 s/month) versus congenital hypothyroidism group (0.1 s/month). Infants with congenital hypothyroidism showed an increase of A3 subtype, of central apnea, and of arousals. The reduction of percentage and mean duration of A1 subtype could be a valuable indicator of sleep development in patients with congenital hypothyroidism and healthy infants.