Screening for Delayed Thyroid Stimulation Hormone Rise and Atypical Congenital Hypothyroidism in Infants Born Very Preterm and Infants with Very Low Birth Weight.

OBJECTIVE: To determine among infants born very preterm (VPT) or with very low birth weight (VLBW) the incidence of alterations in thyroid function and associated comorbidities; the incidence of atypical congenital hypothyroidism (CH) requiring thyroxine therapy; and reference ranges for rescreening at 1 month of age. STUDY DESIGN: A retrospective review of infants born VPT or with VLBW and admitted to UC Irvine Medical Center between January 1, 2012, and December 31, 2020. Repeat thyroid screening was obtained at 1 month of life (+10 days). Infants with thyroid-stimulating hormone (TSH) >5 µIU/mL or free thyroxine <0.8 ng/dL underwent follow-up testing and endocrinology consultation. Initial newborn screening (NBS) and repeat thyroid screening data were collected via chart review. Demographic data and short-term outcomes were abstracted from the California Perinatal Quality Care Collaborative database. RESULTS: In total, 430 patients were included; 64 of 429 patients (14.9%) had TSH >5 µIU/mL and 20 of 421 patients (4.8%) had free thyroxine <0.8 ng/dL. Logistic regression analysis identified small for gestational age (P = .044), patent ductus arteriosus (P = .013), and late-onset sepsis (P = .026) as risk factors associated with delayed TSH rise. Atypical CH requiring treatment through neonatal intensive care unit discharge was diagnosed in 6 patients (incidence of 1.4%); none were identified by NBS. The 90th percentile TSH for infants with extremely low birth weight (<1000 g) was 7.2 µIU/mL, and the 95th percentile for those with birth weight of 1000-1500 g was 6.1 µIU/mL; using these cutoff values identified all infants diagnosed with atypical CH with 100% sensitivity and 90%-95% specificity. CONCLUSIONS: Abnormal thyroid function is common in infants born preterm. Those infants, including some with atypical CH, are missed by NBS. We recommend repeat thyroid screening with TSH at 1 month of age in infants born VPT or infants with VLBW to identify CH that may require therapy.

Clinical and molecular analyses of isolated central congenital hypothyroidism based on a survey conducted in Japan.

Central congenital hypothyroidism (CH) can occur as an isolated deficiency or as part of combined pituitary hormone deficiency. Unlike primary CH, central CH cannot be detected by newborn screening (NBS) using dry filter paper blood TSH levels, and early diagnosis remains challenging. In this study, the clinical and genetic backgrounds of patients with isolated central CH were determined through a questionnaire-based survey among members of the Japanese Society for Pediatric Endocrinology. The known causes of isolated central CH were studied in 14 patients, including six with previously reported patient data. The results revealed IGSF1 and TBL1X pathogenic variants in nine and one patient, respectively. All six patients with low free thyroxine (FT4) levels detected in NBS carried IGSF1 pathogenic variants. Five patients with isolated central CH diagnosed after 3 months of age were variant-negative, except for one female patient with a heterozygous IGSF1 variant. Two of the four variant-negative patients and a variant-positive patient were diagnosed with pituitary hypoplasia. One and two patients with IGSF1 variant had obesity and intellectual disability, respectively. Left amblyopia was identified in the patient with a TBL1X variant. The study revalidated that IGSF1 variants comprise the most frequent pathogenic variant in patients with isolated central CH in Japan. The neonatal period is the optimal time for the diagnosis of central CH, particularly IGSF1 abnormalities, and the introduction of T4 screening should be considered in the future, taking cost-effectiveness into consideration.

Frequency of Mutations in the TPO Gene in Patients with Congenital Hypothyroidism Due to Dyshormonogenesis in Chile.

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

Systematic review of thyroid function in NKX2-1-related disorders: Screening and diagnosis.

BACKGROUND: NKX2-1-related disorders (NKX2-1-RD) are rare conditions affecting lung, thyroid, and brain development, primarily caused by pathogenic variants or deletions in the NKX2-1 gene. Congenital hypothyroidism (CH) is a common endocrine manifestation, leading to irreversible intellectual disability if left untreated. OBJECTIVES: The aim was to evaluate the current evidence for the use of screening and diagnostic techniques for endocrine alterations in patients with NKX2-1-RD. METHODS: This systematic review was reported following the PRISMA guidelines. Two separate research questions in PICO format were addressed to cover initial screening and diagnosis procedures for endocrine diseases in patients with NKX2-1-RD. Eligibility criteria focused on patients with genetic confirmation of the disease and hypothyroidism. Various databases were searched, and data were extracted and assessed independently by two reviewers. RESULTS: Out of 1012 potentially relevant studies, 46 were included, for a total of 113 patients. CH was the most frequent endocrine alteration (45% of patients). Neonatal screening was reported in only 21% of patients based on blood TSH measurements. TSH thresholds varied widely across studies, making hypothyroidism detection ranges difficult to establish. Diagnostic tests using serum TSH were used to diagnose hypothyroidism or confirm its presence. 35% of patients were diagnosed at neonatal age, and 42% at adult age. Other hormonal dysfunctions identified due to clinical signs, such as anterior pituitary deficiencies, were detected later in life. Thyroid scintigraphy and ultrasonography allowed for the description of the thyroid gland in 30% of cases of hypothyroidism. Phenotypic variability was observed in individuals with the same variants, making genotype-phenotype correlations challenging. CONCLUSION: This review highlights the need for standardized protocols in endocrine screening for NKX2-1-RD, emphasizing the importance of consistent methodology and hormone threshold levels. Variability in NKX2-1 gene variants further complicates diagnostic efforts. Future research should concentrate on optimizing early screening protocols and diagnostic strategies.

A novel useful marker in the early discrimination of transient hyperthyrotropinemia/hypothyroxinemia and congenital hypothyroidism in preterm infants: thyroid-stimulating hormone/free thyroxine ratio.

OBJECTIVES: Transient hyperthyrotropinemia/transient hypothyroxinaemia and congenital hypothyroidism (CH) have completely different treatment and clinical outcomes. However, a powerful, highly sensitive and cost-effective marker for the differentiation of these clinical entities in the early postnatal period is not available. Therefore, we aimed to test the potential, early predictive, diagnostic power of the thyroid-stimulating hormone (TSH)/free thyroxine (fT4) ratio for differentiation of the two clinical entities in the early period of life. METHODS: TSH and fT4 levels were recorded on the postnatal day 7 of premature infants<32 weeks of gestational age. TSH/fT4 ratio was calculated. The significance degree of TSH/fT4 ratio was analyzed for the differentiation of transient hyperthyrotropinemia or transient hypothyroxinaemia and CH. RESULTS: The study included 1,204 preterm infants<32 weeks of gestational age. Of the 1,204 infants, 978 (81.2 %) had normal thyroid function. Eighty-eight infants (7.3 %) were diagnosed with CH and 138 (11.5 %) with transient hyperthyrotropinemia or transient hypothyroxinemia. Initial TSH/fT4 ratio>4.8 was found to be an early diagnostic warning sign with high power in favor of transient hyperthyrotropinemia or transient hypothyroxinemia (AUC value: 0.947) and TSH/fT4 ratio>12.5 (AUC value: 0.999) was found to be an early diagnostic warning sign with high power in favor of CH (p=0.0001). CONCLUSIONS: We found for the first time that the TSH/fT4 ratio can be used for the early differentiation of transient hyperthyrotropinemia/transient hypothyroxinaemia and CH in preterm infants without additional cost and with high power.

Clinical efficacy of multigene panels in the management of congenital hypothyroidism with gland in situ.

Congenital hypothyroidism (CHT) is a diverse condition with various genetic etiologies. This study aimed to investigate the utility of next-generation sequencing (NGS) analysis in guiding treatment decisions and predicting prognosis for CHT patients with gland in situ (GIS). A retrospective analysis was conducted on 33 CHT patients with GIS who underwent NGS analysis at a single institution between 2018 and 2023. Patients were classified as having permanent (PCH), transient congenital hypothyroidism, or ambiguous congenital hypothyroidism (ACH) CHT based on their response to levothyroxine discontinuation at 3 years of age. Among the 33 patients, genetic variants were identified in 26, with the most prevalent variants found in DUOX2 (26.92%), TSHR (30.77%), TG (19.35%), and DUOXA2 (19.23%). Patients with high initial thyroid-stimulating hormone levels (>50 mIU/L) and low free thyroxine levels (<0.89 ng/dL) at diagnosis tended to have compound heterozygous or homozygous variants in DUOX2, DUOXA2, and TG, and were more likely to develop PCH. In contrast, patients with heterozygous variants in these genes often exhibited ACH. TSHR variants were associated with diverse clinical manifestations, ranging from PCH to ACH, and were more common in patients with initial thyroid-stimulating hormone levels <50 mIU/L. The study highlights the potential utility of NGS analysis in predicting the clinical course and guiding treatment decisions for CHT patients with GIS. Genetic analysis may aid in determining the appropriate duration of levothyroxine therapy and monitoring strategies, particularly in cases where traditional clinical indicators are inconclusive.

Permanent vs Transient Congenital Hypothyroidism in Chinese Children: Physical Growth and Predictive Nomogram.

CONTEXT: Few reliable markers are available to distinguish transient congenital hypothyroidism (TCH) and permanent congenital hypothyroidism (PCH). Additionally, the differences in growth between TCH and PCH remain unclear. OBJECTIVE: To investigate the growth of children with TCH and PCH and develop a nomogram for early differentiation of these forms. METHODS: This retrospective study included children with TCH or PCH. The predictive efficacy of the prognostic predictors was analyzed using receiver operating characteristic analysis. Multivariate prediction models were developed. Measurements of growth were compared between groups. RESULTS: Patients with TCH had lower initial thyroid-stimulating hormone (TSH) than those with PCH at newborn screening (NBS). The supplementary dose of levothyroxine (L-T4) gradually decreased with age in TCH but not in PCH. The area under the curve (AUC) values of the initial TSH, L-T4 dose at 1 year of age, and L-T4 dose at 2 years of age for distinguishing TCH from PCH were 0.698, 0.71, and 0.879, respectively. The predictive efficacy of the multivariate models at 1 and 2 years of age improved, with AUC values of 0.752 and 0.922, respectively. A nomogram was built based on the multivariate model at 1 year of age. The growth did not differ between children with TCH and those with PCH. However, at 1 year of age, girls with CH exhibited higher z-scores in terms of height and weight than boys with CH. CONCLUSION: TSH at NBS and L-T4 doses during treatment can be used to distinguish between PCH and TCH early in life, and the predictive efficacy can be improved using multivariable models with a visualized nomogram. At 3 years of age, patients with TCH and PCH showed similar growth.

Hipotireoidismo congênito como fator de risco para os transtornos do processamento auditivo central / Congenital hypothyroidism as a risk factor for central hearing process disorders

RESUMO Objetivo: Investigar a manifestação de sintomas do transtorno do processamento auditivo central em crianças com hipotireoidismo congênito. Métodos: Estudo de caráter exploratório, descritivo e transversal com 112 pacientes com hipotireoidismo congênito com idade ≥5 anos. Realizou-se entrevista com os pais/cuidadores no momento da espera da consulta médica. Portadores de outras afecções médicas foram excluídos. Como instrumento de pesquisa utilizou-se o protocolo estruturado de anamnese para avaliação do processamento auditivo rotineiramente empregado por audiologistas. A análise estatística utilizou o teste Qui-quadrado. Resultados: A distribuição por sexo foi semelhante (meninas: 53,3%). Os casos não-disgenesia constituíram a forma fenotípica mais prevalente para o hipotireoidismo congênito (88,4%), e verificou-se que 65,3% das crianças apresentavam algum episódio de níveis séricos irregulares de hormônio tireoestimulante. Dentre as manifestações mais frequentes dos sintomas do transtorno do processamento auditivo central, as queixas relaciondas às funções cognitivas auditivas, como: figura-fundo (83,0%), atenção auditiva (75,9%) e memória auditiva (33,0%) foram as mais evidentes. Reclamações relacionadas ao rendimento escolar foram reportadas em 62,3%. Conclusões: Os dados obtidos evidenciaram altas frequências de sintomas de defasagem nas funções cognitivas relacionadas ao processamento auditivo central, em especial na atenção auditiva, figura-fundo e memória auditiva nos portadores do hipotireoidismo congênito.

ABSTRACT Objective: To investigate the presence of central auditory processing disorder symptoms in children with congenital hypothyroidism. Methods: An exploratory, descriptive, cross-sectional study of 112 patients with congenital hypothyroidism aged ≥5 years old. An interview was held with the parents/caregivers at the time of the medical consultation. Patients with other medical conditions were excluded. As a research instrument, the structured protocol of anamnesis was used to evaluate the auditory processing routinely used by audiologists. For statistical analysis, the chi-square test was used. Results: Sex distribution was similar in both boys and girls (girls: 53.3%). The most prevalent phenotypic form of congenital hypothyroidism was no dysgenesis (88.4%), and 65.3% of the children had an episode of irregular serum thyroid-stimulating hormone (TSH) levels. Among the manifestations of the most frequent central auditory processing disorder symptoms, problems were reported with regard to cognitive functions, as they related to hearing, such as figure-background ability (83.0%), auditory attention (75.9%) and auditory memory (33.0%). Complaints related to school performance were reported in 62.3% of the cases. Conclusions: The data obtained show a high frequency of lag symptoms in cognitive functions related to central auditory processing, particularly with regard to auditory attention, figure-background ability and auditory memory in patients with congenital hypothyroidism.

Evolution to permanent or transient conditions in children with positive neonatal TSH screening tests in Sergipe, Brazil

ABSTRACT Objectives To assess the evolution to permanent or transient conditions in children with positive neonatal TSH tests in Sergipe, Brazil, from 2004 to 2010. Subjects and methods Out of 193,794 screened newborns, 713 presented a neonatal TSH level higher than the local cutoff (5.2 µU/mL). From the confirmatory serum TSH values, the children were diagnosed with initial congenital hypothyroidism (CH) or suspect CH. From the evolution, they were classified as permanent CH, hyperthyrotropinemia, or transient TSH elevation. The mean incidence of each final condition was calculated for the total period of time. Results The initial diagnosis included 37 CH (18.1%) and 167 suspect CH (81.9%) cases. The final diagnosis included 46 cases of permanent CH (22.5%), 56 of hyperthyrotropinemia (27.5%), and 102 of transient TSH elevation (50.0%). Out of the 37 cases of initial CH, 23 (62.2%) had permanent CH, nine (24.3%) had hyperthyrotropinemia, and five (13.5%) had transient TSH elevation. Out of the 167 suspect CH cases, 23 (13.8%) had permanent CH, 47 (28.1%) had hyperthyrotropinemia and 97 (58.1%) had transient TSH elevation. The mean incidence after the follow up was 1:4,166 for permanent CH, 1:3,448 for hyperthyrotropinemia, and 1:1,887 for transient TSH elevation. Eighty-six percent of the children with an initial diagnosis of CH and 41.9% with suspect CH had a permanent condition (CH or hyperthyrotropinemia). Conclusions The follow-up of children with an initial diagnosis of CH or suspect CH is necessary to determine whether the disorder is permanent because predicting the evolution of the condition is difficult.

Effect of Fetal Hypothyroidism on Cardiac Myosin Heavy Chain Expression in Male Rats / O Efeito de Hipotireoidismo Fetal na Expressão da Miosina Cardíaca de Cadeia Pesada em Ratos Macho

Abstract Background: Thyroid hormone deficiency during fetal life could affect the cardiac function in later life. The mechanism underlying this action in fetal hypothyroidism (FH) in rats has not been elucidated thus far. Objective: The aim of this study is to evaluation the effect of FH on cardiac function in male rats and to determine the contribution of α-myosin heavy chain (MHC) and β-MHC isoforms. Methods: Six pregnant female rats were randomly divided into two groups: The hypothyroid group received water containing 6-propyl-2-thiouracil during gestation and the controls consumed tap water. The offspring of the rats were tested in adulthood. Hearts from the FH and control rats were isolated and perfused with langendroff setup for measuring hemodynamic parameters; also, the heart mRNA expressions of α- MHC and β-MHC were measured by qPCR. Results: Baseline LVDP (74.0 ± 3.1 vs. 92.5 ± 3.2 mmHg, p < 0.05) and heart rate (217 ± 11 vs. 273 ± 6 beat/min, p < 0.05) were lower in the FH rats than controls. Also, these results showed the same significance in ±dp/dt. In the FH rats, β-MHC expression was higher (201%) and α- MHC expression was lower (47%) than control. Conclusion: Thyroid hormone deficiency during fetal life could attenuate normal cardiac functions in adult rats, an effect at least in part due to the increased expression of β-MHC to α- MHC ratio in the heart.

Resumo Fundamento: Deficiência de hormônio da tireoide durante vida fetal pode afetar a função cardíaca no futuro. O mecanismo subjacente dessa ação em hipotireoidismo fetal (HF) em ratos ainda não tem explicação. Objetivo: O objetivo desse estudo é avaliar o efeito de HF na função cardíaca em ratos macho e determinar a contribuição da α-miosina de cadeia pesada (α-MCP) e de isoformas β-MCP. Métodos: Seis ratos fêmea gestantes foram aleatoriamente divididas em dois grupos. O grupo do hipotireoidismo recebeu água contendo 6-propil-2-tiouracil durante a gestação, e os ratos no grupo de controle receberam água de torneira. Os filhotes dos ratos foram testados quando atingiram idade adulta. O coração dos ratos HF e controle foram isolados e submetidos a perfusão pelo método de Langendorff para medição de parâmetros hemodinâmicos. Também foram medidas as expressões de mRNA do coração de α-MCP e β-MCP por qPCR. Resultados: PVED de base (74,0 ± 3,1 vs. 92,5 ± 3,2 mmHg, p < 0,05) e pressão arterial (217 ± 11 vs. 273 ± 6 batidas/min, p < 0,05) mostraram-se mais baixas em ratos HF do que em ratos controle. Além disso, esses resultados mostraram a mesma significância em ±dp/dt. Em ratos HF, a expressão de β-MCP foi mais alta (201%) e a de α-MCP foi mais baixa (47%) do que em ratos controle. Conclusão: Deficiência de hormônio da tireoide durante a vida fetal pode enfraquecer funções cardíacas normais em ratos adultos, efeito devido em parte à expressão aumentada de β-MCP em relação a α-MCP no coração.

Large thyroid cyst in a patient with congenital hypothyroidism / Grande cisto tiroidiano em paciente com hipotireoidismo congênito

Thyroid hormone biosynthetic defects are rare causes of congenital hypothyroidism. Although, initial presentations are usually diffuse goiter and hypothyroidism, subsequently they may develop thyroid nodules and or thyroid cancer. We describe a case of hypothyroidism due to dyshormonogenesis whose one of the previously solid nodules degenerates into a large cyst. A 22-year-old male was referred to our clinic for evaluation of enlarging thyroid nodule. Hypothyroidism was diagnosed in infancy, however due to poor compliance to treatment TSH values were elevated most of the times. When he was fifteen the first nodule was detected which was a solid cold nodule. Fine needle aspiration was in favor of benign follicular nodule. Seven years later we found a large multi nodular thyroid with a predominant large cyst corresponding to the previously detected solid nodule. 21cc straw colored fluid was aspirated. Cytology was reported as benign cystic nodule. The patient underwent thyroidectomy and pathology confirmed a benign thyroid cyst. Although underreported thyroid dyshormonogenesis may progress to cystic degeneration. Taking into account the risk of malignancy and eventually cyst formation, we recommend more frequent evaluation in the face of nodule formation in these patients. Arq Bras Endocrinol Metab. 2014;58(9):958-61.

Os defeitos de biossíntese do hormônio tiroidiano são causas raras de hipotireoidismo congênito. Embora as apresentações iniciais sejam geralmente bócio difuso e hipotireoidismo, nódulos tiroidianos ou câncer de tiroide podem se desenvolver subsequentemente. Descrevemos aqui um caso de hipotireoidismo causado por disormonogênese e no qual um dos nódulos sólidos degenerou em um grande cisto. Um homem de 22 anos de idade foi encaminhado para nossa clínica para avaliação do aumento de um nódulo tiroidiano. O hipotireoidismo foi diagnosticado na infância. Entretanto, em razão da baixa conformidade ao tratamento, os valores de TSH estavam elevados na maior parte do tempo. Quando o paciente tinha 15 anos de idade, um primeiro nódulo sólido e frio foi detectado. A aspiração por agulha fina mostrou um nódulo folicular benigno. Sete anos depois encontramos múltiplos nódulos na tiroide e um grande cisto predominante que correspondia ao nódulo sólido anteriormente detectado. Foram aspirados 21cc de fluido cor de palha. A citologia mostrou um nódulo cístico benigno. O paciente foi submetido à tiroidectomia e o exame histopatológico confirmou um cisto tiroidiano benigno. Embora não seja comumente relatada, a disormonogênese da tiroide pode progredir para a degeneração cística. Ao serem considerados o risco de malignidade e a eventual formação de cistos, recomendamos uma avaliação mais frequente da formação de nódulos nesses pacientes. Arq Bras Endocrinol Metab. 2014;58(9):958-61.

Hipotireoidismo congênito: perfil clínico dos recém-nascidos identificados pelo Programa de Triagem Neonatal de Minas Gerais / Congenital hypothyroidism: the clinical profile of affected newborns identified by the Newborn Screening Program of the State of Minas Gerais, Brazil

OBJETIVO: Avaliar o perfil clínico de recém-nascidos com hipotireoidismo congênito identificados pelo Programa Estadual de Triagem Neonatal de Minas Gerais entre 2000 e 2006. MÉTODOS: A frequência das manifestações clínicas de hipotireoidismo congênito foi analisada em relação aos níveis de hormônio estimulante da tireoide T4L (determinados por quimioluminescência, valores de referência de 0,3 a 5,0 µUI/mL e 0,8 a 1,8 ng/dL, respectivamente) e idades ao diagnóstico e tratamento. Estudou-se 443 crianças, sendo 55,8 por cento do sexo feminino e 95 por cento delas com menos 60 dias de vida. RESULTADOS: Os sinais clínicos mais prevalentes foram: hérnia umbilical (51 por cento), fontanela anterior ampla (50,3 por cento) e fontanela posterior aberta (47,2 por cento). Hipotonia, macroglossia e sucção débil foram os sinais mais associados com a gravidade bioquímica da doença. Em 32,1 por cento das crianças houve atraso na idade óssea ao diagnóstico. As medianas de TSH e T4L séricos foram 120 µUI/mL e 0,62 ng/dL, respectivamente. A mediana da idade de início de tratamento foi de 28 dias. CONCLUSÃO: Existem sinais clínicos precoces que sugerem o diagnóstico de hipotireoidismo congênito. Portanto, diante de uma criança com esses sinais, devem ser avaliados TSH e T4L séricos para confirmar ou excluir a doença, independentemente do resultado do teste de triagem. A idade de início de tratamento ainda foi elevada, mas o programa vem adotando estratégias para redução da mesma.

OBJECTIVE: To evaluate the clinical profile of newborns with congenital hypothyroidism identified by the Newborn Screening Program of the State of Minas Gerais, Brazil, between 2000 and 2006. METHODS: Analysis of factors involved in this profile, including: TSH and FT4 levels (determined by chemiluminescence, with limits of normality set at 0.3-5.0 µUI/mL and 0.8-1.8 ng/dL, respectively), age at diagnosis and age at treatment. The study sample consisted of 443 children, 55.8 percent were female and 95 percent were seen before completing 60 days of life. RESULTS: The most prevalent clinical signals were: umbilical hernia (51 percent), enlarged anterior fontanel (50.3 percent), and open posterior fontanel (47.2 percent). Hypotonia, macroglossia and feeding difficulties were the clinical signs most frequently associated with the biochemical severity of the disease. A delay in bone age was present in 32.1 percent of the children at diagnosis. The median of serum TSH and FT4 was 120 µUI/mL and 0.62 ng/dL, respectively. The median age at start of treatment was 28 days. CONCLUSION: There are some early clinical signs that suggest a diagnosis of congenital hypothyroidism. Therefore, when presented with a child exhibiting these signs, serum TSH and FT4 should be assayed in order to confirm or rule out the disease, irrespective of the result of screening. Age at start of treatment remains high, but strategies are being implemented to reduce it.

Densidade mineral óssea de crianças e adolescentes com hipotireoidismo congênito / Bone mineral density of children and adolescents with congenital hypothyroidism

Realizou-se estudo transversal com 60 pacientes (9,9 ± 1,8 anos) com hipotireoidismo congênito (HC) (grupo A): 40 meninas (23 pré-púberes) e 20 meninos (18 pré-púberes), com grupo controle (grupo B) constituído por 28 indivíduos (10,4 ± 2,1 anos): 18 meninas (8 pré-púberes) e 10 meninos (9 pré-púberes). OBJETIVOS: Avaliar a densidade (DMO) e o conteúdo mineral ósseo (CMO) e correlacioná-los com idade cronológica e óssea (IO), sexo, maturação sexual, dose de l-T4, TSH, TT4, FT4, e etiologia do HC. IO, DMO e CMO de corpo total (DXA) foram obtidos dos 2 grupos; TSH, TT4 e FT4, apenas dos pacientes. DMO foi menor no grupo A (0,795 ± 0,075 g/cm² vs. 0,832 ± 0,092; p = 0,04) e maior nas meninas púberes do que nas pré-púberes (p = 0,004). Não houve diferença significativa de DMO e CMO quanto ao sexo e etiologia do HC. Nosso estudo mostra que a DMO foi significativamente menor no grupo com HC, diferente dos dados da literatura.

A cross sectional study was made on 60 patients (9.9 ± 1.8 yr-old) with congenital hypothyroidism (CH) (group A): 40 girls (23 prepubertal) and 20 boys (18 prepubertal). Control group (group B) was constituted of 28 healthy children (10.4 ± 2.1 yr-old): 18 girls (8 prepubertal) and 10 boys (9 prepubertal). AIMS: To evaluate bone mineral density (BMD) and content (BMC) and to correlate them with chronological and bone age (BA), sex, sexual maturation, l-T4 dose, TSH, TT4, FT4, and CH etiology. BA, total body BMD, and BMC (DXA) were obtained of both groups. TSH, TT4, and FT4 were measured in patients only. BMD was lower in group A (0.795 ± 0.075 g/cm² vs. 0.832 ± 0.092; p = 0.04) and higher in pubertal than in prepubertal girls (p = 0.004). There was no significant difference between BMD and BMC related to sex and CH etiology. Our data demonstrated that BMD was significantly lower in children with CH, different from what has been published in the literature.

Hipotiroidismo congênito transitório: perfil das crianças identificadas no programa estadual de triagem neonatal de Minas Gerais, Brasil / Congenital transient hypothyroidism: characteristics of children identified at newborn screening program of the state of Minas Gerais, Brazil

O diagnóstico e o tratamento precoces do hipotiroidismo congênito (HC) constituem os principais objetivos dos programas de triagem neonatal. Neste estudo avaliou-se o perfil hormonal e os possíveis fatores responsáveis pelo HC transitório (HCT). Os dados foram colhidos dos prontuários das crianças acompanhadas no Hospital das Clínicas da UFMG, triadas pelo Programa Estadual de Triagem Neonatal de Minas Gerais. Para o diagnóstico de HCT considerou-se: exames de triagem e sérico confirmatório alterados; TSH e T4 livre normais em 4 e 8 semanas após suspensão do tratamento hormonal para avaliação etiológica. As 21 crianças com HCT representavam 4,23 por cento das crianças acompanhadas pelo Programa e receberam tratamento com L-tiroxina por um mês a três anos. Os valores de TSH no primeiro exame sérico variaram de 10,4 a 583,4æUI/ml, não se correlacionando, portanto, à gravidade da doença. Possivelmente a presença de anticorpos maternos em duas crianças, anti-TPO (anticorpo anti-tireoperoxidase) em uma e o anticorpo anti-receptor de TSH associado à exposição ao iodo em outra foram responsáveis pelo hipotiroidismo. Concluímos que o HCT é uma entidade importante na triagem neonatal, sendo essencial o tratamento hormonal nos primeiros meses de vida e que os níveis iniciais de TSH não são úteis para definir se a disfunção tiroidiana será transitória ou permanente.