[Cognitive performance of preschoolers with Congenital Hypothyroidism enrolled in a follow-up program]. / Desempeño cognitivo en preescolares con Hipotiroidismo Congénito incorporados en un programa de seguimiento.

The age at treatment initiation is decisive for limiting the neurological sequelae of Congenital Hypothyroidism (CH). Incorporating children into follow-up programs could be very helpful. OBJECTIVE: To evaluate the cognitive performance of preschool children with CH incorporated into a follow- up program. PATIENTS AND METHOD: Prospective study of 93 patients with a confirmed diagnosis of CH. Intelligence quotient (IQ) was assessed using the Wechsler Preschool and Primary Intelligence Scale (WPPSI) at 4 and 5 years, and the WISC-R at 6 years of age. Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Performance IQ (PIQ) scores were analyzed. RESULTS: The study sample was 80 children. The average age at starting hormonal treatment was 42 ± 18 days; treatment started early in 25 patients (24 ± 6 days) and late in 55 patients (50 ± 16 days). The mean initial dose of Levothyroxine was 13.5 ± 1.5µg/kg/day. Children with athyrosis and late initiation of treatment had lower scores on the VIQ (85 ± 14), the PIQ (89 ± 12), and the FSIQ (86 ± 13) scales at 4 years of age, in comparison with patients with early initiation of treatment. These patients scored within the cut-off point for the normal IQ classification (90-109 points). IQ comparison at 6 years of age revealed differences up to 14 points in the PIQ and 11 points in the FSIQ between children with athyrosis and early initiation of treatment, with and without regular attendance to the follow-up program. DISCUSSION: These results support the importance of early initiation of treatment and the incorporation of children in follow-up programs and early stimulation. The etiology of hypothyroidism and the age at initiation of treatment were the most significant factors that affected cognitive performance.

Atipicidad en el hipotiroidismo congénito: síndrome de Kocher-Debré-Semelaigne. Reporte de caso / Atypicality in congenital hypothyroidism: Kocher-Debré-Semelaigne. Case report

El síndrome de Kocher Debré Semelaigne (SKDS) se describe dentro de las formas clínicas atípicas asociadas al hipotiroidismo congénito (HC) severo, no tratado y de larga evolución, con manifestaciones de pseudohipertrofia muscular difusa y debilidad muscular predominantemente proximal, reversible al reemplazo con tiroxina. Es raro en países con programas de pesquisa neonatal. Objetivo: reportar el caso de un niño con diagnóstico de HC por disembriogenesis (atireosis), que se mantuvo con mal control de la enfermedad durante el primer año de vida y manifestaciones miopáticas desde la etapa neonatal. Resultados: se confirma el diagnóstico a través de estudios específicos, con evidencias de patrones miopáticos característicos. Se logra regresión clínica parcial a los nueve meses de mantener estabilidad de la TSH y las hormonas tiroideas (HT), coincidiendo con la normalización de la enzima de músculo creatinfosfoquinasa (CPK). A los 12 años de seguimiento, mantenía ligera hipertrofia de la musculatura de las extremidades superiores, dorsales y glúteos, a pesar de mantenerse eutiroideo. Conclusiones: la presencia de hipertrofia muscular debe considerarse un dato clínico de sospecha de hipotiroidismo, aun con la implementación de los programas de pesquisa neonatal. Es posible la regresión parcial de la pseudohipertrofia muscular con el restablecimiento de la función tiroidea. Se debe tomar en cuenta en el diagnóstico diferencial de otras miopatías primarias

Kocher-Debré-Semelaigne Syndrome (SKDS) is described within the atypical clinical forms associated with severe, untreated and long-standing congenital hypothyroidism with manifestations of diffuse muscle pseudohypertrophy and predominantly proximal muscle weakness, reversible to replacement with levothyroxine. objective: To report the case of a child with congenital hypothyroidism due to disembriogenesis (atyreosis), who remained with poor control of the disease during the 1st year of life and myopathic manifestations from de neonatal stage. Results: The diagnosis is confirmed through specific studies, with evidence of characteristic myopathic patterns. Partial clinical regression is achieved 9 months after maintaining stability of TSH and thyroid hormones, coinciding with the normalization of the muscle enzyme creatine phosphokinase (CPK). At 12 years of follow-up, he maintained slight hypertrophy of the muscle of the upper extremities, dorsal and buttocks, despite remaining euthyroid. Conclusions: The presence of muscular hypertrophy should be considered a clinical finding of suspected hypothyroidism, even with the implementation of neonatal screening programs. Partial regression of muscle pseudohypertrophy is possible with restoration of thyroid function, and should be taken into account in the differential diagnosis of other primary myopathies

An Intramolecular Ionic Interaction Linking Defective Sodium/Iodide Symporter Transport to the Plasma Membrane and Dyshormonogenic Congenital Hypothyroidism.

Background: The sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Autosomal recessive iodide transport defect (ITD)-causing loss-of-function NIS variants lead to dyshormonogenic congenital hypothyroidism due to deficient iodide accumulation for thyroid hormonogenesis. Here, we aimed to identify, and if so to functionally characterize, novel ITD-causing NIS pathogenic variants in a patient diagnosed with severe dyshormonogenic congenital hypothyroidism due to a defect in iodide accumulation in the thyroid follicular cell, as suggested by nondetectable radioiodide accumulation in a normally located thyroid gland, as well as in salivary glands. Methods: The proposita NIS-coding SLC5A5 gene was sequenced using Sanger sequencing. In silico analysis and functional in vitro characterization of the novel NIS variants were performed. Results: Sanger sequencing revealed novel compound heterozygous SLC5A5 gene variants (c.970-3C>A and c.1106A>T, p.D369V). In silico analysis suggested that c.970-3C>A disrupts the canonical splice acceptor site located in intron 7. Splicing minigene reporter assay revealed that c.970-3C>A causes exon 8 skipping during NIS pre-mRNA splicing leading to the NIS pathogenic variant p.Y324Hfs*148. Moreover, in silico analysis indicated p.D369V as pathogenic. Functional in vitro studies demonstrated that p.D369V NIS does not mediate iodide accumulation, as p.D369V causes NIS to be retained in the endoplasmic reticulum. Mechanistically, we propose an intramolecular ionic interaction involving the ß carboxyl group of D369 and the guanidinium group of R130, located in transmembrane segment 4. Of note, an Asp residue at position 369-which is highly conserved in SLC5A family members-is required for functional NIS expression at the plasma membrane. Conclusions: We uncovered a critical intramolecular interaction between R130 and D369 required for NIS maturation and plasma membrane expression. Moreover, we identified the first intronic variant causing aberrant NIS pre-mRNA splicing, thus expanding the mutational landscape in the SLC5A5 gene leading to dyshormonogenic congenital hypothyroidism.

ADHESION TO TREATMENT BY CHILDREN WITH CONGENITAL HYPOTHYROIDISM: KNOWLEDGE OF CAREGIVERS IN BAHIA STATE, BRAZIL.

OBJECTIVE: To investigate knowledge of caregivers of children with congenital hypothyroidism (CH), followed in a public reference service, as well as their associations with treatment adherence. METHODS: Exploratory, descriptive, cross-sectional study with convenience sample. Medical records of 158 patients diagnosed with congenital hypothyroidism were analyzed, and data were evaluated by applying a previously prepared questionnaire to caregivers from 2014 to 2016. Statistical analysis used the chi-square and the Spearman's correlation tests, being significant p-value ≤0.05. RESULTS: Females were predominant among caregivers (94.3%), with a mean age of 31 years, from inland cities (77.8%). There was a predominance of socioeconomic class C (59.5%) and incomplete primary education (35.7%). More than half of patients (53.2%) with CH had an adequate hormonal control. Approximately one third of caregivers had poor knowledge (37.3%) or was unaware (24.1%) about the meaning of congenital hypothyroidism. The low knowledge level of the disease was observed to be related to caregivers' educational level (p=0.004). CONCLUSIONS: Lack of education of caregivers was a barrier to be faced when monitoring children with CH. This reality requires greater attention from health professionals to ensure that they use clear language when giving instructions to caregivers, and that caregivers have adequately understood the proposed recommendations.

[Formula: see text]Socioeconomic aspects are crucial to better intellectual outcome in early-treated adolescents with congenital hypothyroidism.

Congenital hypothyroidism (CH) is an important cause of preventable intellectual disability. Implementation of CH neonatal screening programs leading to early treatment has improved cognitive outcome. However, more subtle cognitive impairments are still reported, and there is lack of clarity regarding factors that impact long-term cognitive outcome. Research to better understand these factors can lead to further improvements in the cognitive prognosis for these patients. The current study aimed to evaluate the cognitive performance of adolescents who were early-treated for primary permanent CH and possible associated variables. Neurocognitive evaluation was carried out in 66 adolescents, 11 to 16 years old: 34 with CH and 29 paired controls. Intellectual quotient (IQ), verbal fluency, processing speed, executive functions, and memory were investigated. CH patients and control subjects were comparable regarding sex, age, schooling, family's socioeconomic status and caregiver's educational level. Both groups presented not only similar IQ scores but also equivalent performances regarding Perceptual Reasoning, Working Memory and Processing Speed index scores. Patients presenting different CH etiologies (dysgenesis and dyshormonogenesis) showed similar cognitive performance. Socioeconomic aspects along with the initial levothyroxine dose were the main variables to positively influence the cognitive performance, the family's socioeconomic status having the strongest association with patients' cognitive skills.

Adhesion to treatment by children with congenital hypothyroidism: knowledge of caregivers in bahia state, brazil / Adesão ao tratamento de crianças com hipotireoidismo congênito: o conhecimento dos cuidadores no estado da bahia, brasil

ABSTRACT Objective: To investigate knowledge of caregivers of children with congenital hypothyroidism (CH), followed in a public reference service, as well as their associations with treatment adherence. Methods: Exploratory, descriptive, cross-sectional study with convenience sample. Medical records of 158 patients diagnosed with congenital hypothyroidism were analyzed, and data were evaluated by applying a previously prepared questionnaire to caregivers from 2014 to 2016. Statistical analysis used the chi-square and the Spearman's correlation tests, being significant p-value ≤0.05. Results: Females were predominant among caregivers (94.3%), with a mean age of 31 years, from inland cities (77.8%). There was a predominance of socioeconomic class C (59.5%) and incomplete primary education (35.7%). More than half of patients (53.2%) with CH had an adequate hormonal control. Approximately one third of caregivers had poor knowledge (37.3%) or was unaware (24.1%) about the meaning of congenital hypothyroidism. The low knowledge level of the disease was observed to be related to caregivers' educational level (p=0.004). Conclusions: Lack of education of caregivers was a barrier to be faced when monitoring children with CH. This reality requires greater attention from health professionals to ensure that they use clear language when giving instructions to caregivers, and that caregivers have adequately understood the proposed recommendations.

RESUMO Objetivo: Investigar o conhecimento dos cuidadores das crianças com hipotireoidismo congênito (HC) acompanhadas em um serviço público de referência, bem como as suas associações com a adesão ao tratamento. Métodos: Trata-se de um estudo exploratório, descritivo, de corte transversal, com amostra de conveniência. Foram analisados os prontuários de 158 pacientes com diagnóstico de HC e avaliados os dados obtidos pela aplicação de um questionário previamente elaborado, destinado aos cuidadores, durante o período de 2014 a 2016. A análise estatística foi feita com o teste do qui-quadrado e a Correlação de Spearman, para correlacionar a pontuação do questionário, sendo significante o valor de p≤0,05. Resultados: Os cuidadores eram predominantemente do sexo feminino (94,3%), com média de idade de 31 anos, proveniente de cidades do interior (77,8%). Verificou-se predomínio da classe socioeconômica C (59,5%) e ensino fundamental incompleto (35,7%) na amostra dos cuidadores. Metade dos pacientes (53,2%) apresentava controle hormonal adequado. Aproximadamente 1/3 dos cuidadores demonstraram conhecimento ruim (37,3%) ou até mesmo desconheciam (24,1%) o HC. Observou-se que o baixo nível de conhecimento da doença estava diretamente relacionado com o nível educacional dos cuidadores (p=0,004). Conclusões: Os achados sugerem que a falta de instrução dos cuidadores é uma barreira a ser enfrentada durante o acompanhamento de crianças com HC, o que requer uma maior atenção do profissional de saúde, para garantir uma linguagem clara e um entendimento adequado das recomendações propostas.

Pubertal development and adult height in patients with congenital hypothyroidism detected by neonatal screening in southern Brazil.

Objectives Adequate treatment of congenital hypothyroidism (CH) is required for normal growth and sexual development. To evaluate pubertal development in patients with permanent CH detected by a statewide Neonatal Screening Program of Paraná and, secondly, to evaluate adult height (AH) in a subgroup of patients. Methods Clinical, laboratory, and auxological data obtained from medical records of 174 patients (123 girls). Results Median chronological age (CA) at treatment initiation was 24 days, and mean initial levothyroxine dose was 11.7 ± 1.9 µg/kg/day; mean CA at puberty onset was 11.5 ± 1.3 years (boys) and 9.7 ± 1.2 years (girls); mean CA in girls who underwent menarche (n=81) was 12.1 ± 1.1 years. Thyroid-stimulating hormone (TSH) values above the normal range were observed in 36.4% of the boys and 32.7% of the girls on puberty onset, and in 44.6% around menarche. Among 15 boys and 66 girls who had reached the AH, the median height z-score value was significantly greater than the target height (TH) z-score value in boys (p=0.01) and in girls (p<0.001). Boys with normal TSH values at puberty onset had greater mean AH z-score compared with boys with TSH values above the normal range (p=0.04). Conclusions In this group, pubertal development in girls with CH was not different from that reported in healthy girls in the general Brazilian population. Boys with higher TSH at puberty onset may have an increased risk of not reaching their potential height compared with those with normal TSH during this period. In a subgroup who attained AH, the median AH z-score was greater than the median TH z-score.

Cluster of cases of congenital feline goitrous hypothyroidism in a single hospital.

OBJECTIVES: To describe the clinicopathological findings and outcomes of cases of feline congenital hypothyroidism diagnosed in a single veterinary hospital in Santiago, Chile. MATERIALS AND METHODS: Medical records were searched for cases of congenital hypothyroidism over an 18-month period. Inclusion criteria were a diagnosis of congenital hypothyroidism based on consistent historical and clinical findings, a low or low-normal serum total T4 and elevated serum canine TSH (cTSH). RESULTS: Six unrelated cats ranging in age from 4 to 19 months met the inclusion criteria. The most common historical signs were small stature and lethargy. All cats had disproportionate dwarfism, delayed tooth eruption, retained deciduous teeth, bilateral palpable goitres and low rectal temperatures. Other findings were bradycardia, obesity, poor hair coat and focal alopecia on the ventral aspects of the elbows and hocks. In all cases, cTSH was markedly elevated. Sequential changes noted after the initiation of therapy included normal T4 after 6 weeks, improved hair coat and increased physical activity by 8 weeks, normal cTSH by 10 weeks and normal physical appearance and dentition after 4 months. Goitres shrank markedly but remained palpable. Hypothyroidism was well managed clinically in all cases 2 years after diagnosis except for one cat that died of unrelated causes. CLINICAL SIGNIFICANCE: This is the first report to describe a cluster of congenital hypothyroidism cases in non-related cats that were presented over a short period of time. Growth defects resolve with treatment, even in cats diagnosed after puberty. Larger, prospective multi-centre studies are warranted to determine the incidence of congenital hypothyroidism in cats.

Inclusão das apresentações de Levotiroxina sódica de 12, 5 e 37, 5 mcg para tratamento do hipotireoidismo congênito / Inclusion of Levothyroxine sodium presentations of 12. 5 and 37. 5 mcg for treatment of congenital hypothyroidism

CONTEXTO: O hipotireoidismo congênito (HC) é a doença congênita mais comum do sistema endócrino e a principal causa de deficiência mental passível de prevenção no mundo. No Brasil, a incidência do HC é de aproximadamente um caso para cada 2.595 a 4.795 nascidos vivos. O prognóstico depende, fundamentalmente, do tempo decorrido para instituição do tratamento, da severidade do hipotireoidismo e da manutenção dos níveis hormonais dentro da normalidade. O tratamento é realizado com o medicamento levotiroxina e deve ser instituído o mais breve possível para evitar prejuízos no desenvolvimento mental e no crescimento da criança. JUSTIFICATIVA DA DEMANDA: As apresentações de levotiroxina sódica disponíveis na Rename e indicados no PCDT para o tratamento do HC são os comprimidos de 25, 50 e 100 mcg. A necessidade de ajustes posológicos de acordo com o crescimento da criança e dos níveis de TSH e T4 livre ou total tornam necessários ajustes posológicos frequentes. A utilização de apresentações intermediárias como de 12,5 mcg e 37,5 mcg reduzem a necessidade de utilização de comprimidos partidos para complementação das doses, minimizando erros de administração, ajustes de doses mais fidedignos a necessidade e o desperdício dos comprimidos. Em reunião de escopo para revisão do PCDT da HC realizada em 11/09/2019, na qual estavam presentes metodologistas, especialistas em endocrinologia e membros do DGITIS, foi sugerida a avaliação da incorporação das apresentações de 12,5 e 37,5 mcg de levotiroxina sódica para os pacientes com HC. DELIBERAÇÃO FINAL: Diante do exposto, a Conitec, em sua 88ª reunião ordinária, realizada no dia 8 de julho de 2020, deliberou por unanimidade recomendar a incorporação das apresentações de 12,5 e 37,5 mcg de levotiroxina sódica para o tratamento do Hipotireoidismo congênito no Sistema Único de Saúde. Assim, foi assinado o registro de deliberação nº 536/2020. DECISÃO: Incorporar as apresentações de 12,5 e 37,5 mcg de levotiroxina sódica para o tratamento de pacientes com hipotireoidismo congênito, conforme protocolo do Ministério da Saúde, no âmbito do Sistema Único de Saúde ­ SUS, conforme Portaria n° 38, publicada no Diário Oficial da União n° 181, seção 1, página 235, em 21 de setembro de 2020.

Treatment Discontinuation within 3 Years of Levothyroxine Initiation among Children Diagnosed with Congenital Hypothyroidism.

OBJECTIVES: To measure the rates of thyroid gland imaging and levothyroxine (L-T4) discontinuation and to assess whether discontinuation was monitored with thyroid-stimulating hormone testing in subjects with congenital hypothyroidism. STUDY DESIGN: This is a retrospective analysis of claims data from the IBM MarketScan Databases for children born between 2010 and 2016 and continuously enrolled in a noncapitated employer-sponsored private health insurance plan or in Medicaid for ≥36 months from the date of the first filled L-T4 prescription. RESULTS: There were 263 privately insured and 241 Medicaid-enrolled children who met the inclusion criteria. More privately insured than Medicaid-enrolled children had imaging between the first filled prescription and 180 days after the last filled prescription (24.3% vs 12.9%; P = .001). By 36 months, 35.7% discontinued L-T4, with no difference by insurance status (P = .48). Among those who discontinued, 29.1% of privately insured children and 47.7% of Medicaid-enrolled children had no claims for thyroid-stimulating hormone testing within the next 180 days (P = .01). CONCLUSIONS: Nearly one-third of children with suspected congenital hypothyroidism discontinued L-T4 by 3 years and fewer Medicaid-enrolled than privately insured children received timely follow-up thyroid-stimulating hormone testing. Future studies are indicated to understand the quality of care and developmental outcomes for children with congenital hypothyroidism and barriers to guideline adherence in evaluating for transient congenital hypothyroidism.

Novel Sodium/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism.

Iodide transport defect (ITD) is an autosomal recessive disorder caused by deficient iodide accumulation into the thyroid follicular cell. ITD is an uncommon cause of dyshormonogenetic congenital hypothyroidism that results from inactivating mutations in the sodium/iodide symporter (NIS)-coding SLC5A5 gene. NIS is a key basolateral plasma membrane glycoprotein that efficiently mediates active iodide uptake in the thyroid-constituting the first step in the biosynthesis of the iodine-containing thyroid hormones-and other tissues, including salivary glands, lactating breast, and small intestine. The proposita, a 20-day-old female born in 1992, was diagnosed with congenital hypothyroidism through newborn screening. ITD was suspected on the basis of nondetectable radioiodide accumulation in a normally located nongoitrous thyroid gland, as well as in salivary glands. Sanger sequencing revealed nonpreviously reported compound heterozygous missense SLC5A5 gene variants (c.991G>A, p.D331N and c.1.641C>A, p.S547R). Notably, these variants have not been reported in public databases (i.e., Exome Aggregation Consortium, 1000 Genomes, and Single Nucleotide Polymorphism). In silico analysis using prediction softwares (i.e., SIFT, Polyphen-2, and MutationTaster2) support the pathologic significance of p.D331N and p.S547R NIS. Moreover, functional in vitro studies demonstrate that D331N and S547R NIS severely reduce iodide uptake when the proteins are heterologously expressed in HEK-293T cells because of a pronounced impairment of D331N and S547R NIS targeting to the plasma membrane. Of note, a charged residue at position 331 and a serine residue at position 547-which are highly conserved in SLC5A family members-are required for NIS plasma membrane targeting. We report two novel missense pathogenic variants in a compound heterozygous state in the SLC5A5 gene, detected through Sanger sequencing, in a pediatric female patient with dyshormonogenic congenital hypothyroidism.

Neonatal screening: 9% of children with filter paper thyroid-stimulating hormone levels between 5 and 10 µIU/mL have congenital hypothyroidism / Triagem neonatal: 9% das crianças com TSH em papel filtro entre 5 e 10 µUI/mL têm hipotireoidismo congênito

Abstract Objectives: To determine the prevalence of congenital hypothyroidism in children with filter-paper blood-spot TSH (b-TSH) between 5 and 10 µIU/mL in the neonatal screening. Methods: This was a retrospective study including children screened from 2003 to 2010, with b-TSH levels between 5 and 10 µIU/mL, who were followed-up during the first two years of life when there was no serum TSH normalization. The diagnosis of congenital hypothyroidism was defined as serum TSH ≥10 µIU/mL and start of levothyroxine treatment up to 2 years of age. Results: Of the 380,741 live births, 3713 (1.04%) had filter paper TSH levels between 5 and 10 µIU/mL and, of these, 339 (9.13%) had congenital hypothyroidism. Of these, 76.11% of the cases were diagnosed in the first three months of life and 7.96% between 1 and 2 years of age. Conclusion: The study showed that 9.13% of the children with b-TSH levels between 5 and 10 µIU/mL developed hypothyroidism and that in approximately one-quarter of them, the diagnosis was confirmed only after the third month of life. Based on these findings, the authors suggest the use of a 5 µIU/mL cutoff for b-TSH levels and long-term follow-up of infants whose serum TSH has not normalized to rule out congenital hypothyroidism.

Resumo Objetivos: Determinar a prevalência de hipotireoidismo congênito em crianças com TSH em papel filtro (TSH-f) entre 5 e 10 µUI/mL na triagem neonatal. Métodos: Estudo retrospectivo que incluiu crianças triadas de 2003 a 2010, com TSH-f entre 5 e 10 µUI/mL, acompanhadas nos dois primeiros anos de vida quando não houve normalização do TSH sérico. O diagnóstico de hipotireoidismo congênito foi definido como TSH sérico igual ou superior a 10 µUI/mL e início de tratamento com levotiroxina até os dois anos. Resultados: Dos 380.741 nascidos vivos triados, 3.713 (1,04%) apresentaram TSH-f entre 5 e 10 µUI/mL e, desses, 339 (9,13%) tinham hipotireoidismo congênito. Desses, 76,11% dos casos foram diagnosticados nos primeiros três meses de vida e 7,96% entre um e dois anos. Conclusão: O estudo mostra que 9,13% das crianças com TSH-f entre 5 e 10 µUI/mL desenvolveram hipotireoidismo e que em cerca de um quarto delas o diagnóstico só se confirmou após o terceiro mês de vida. Com base nesses achados, sugere-se, para descartar o hipotireoidismo congênito, o uso do ponto de corte de TSH-f de 5 µUI/mL e o acompanhamento em longo prazo dos lactentes cujo TSH sérico não tenha se normalizado.

Timing of thyroid ultrasonography in the etiological investigation of congenital hypothyroidism

ABSTRACT Objectives To describe the findings of thyroid ultrasonography (T-US), its contribution to diagnose congenital hypothyroidism (CH) and the best time to perform it. Subjects and methods Forty-four patients with CH were invited to undergo T-US and 41 accepted. Age ranged from 2 months to 45 years; 23 patients were females. All were treated with L-thyroxine; 16 had previously undergone scintigraphy and 30 had previous T-US, which were compared to current ones. Results At the current T-US, the thyroid gland was not visualized in its normal topography in 10 patients (24.5%); 31 T-US showed topic thyroid, 17 with normal or increased volume due to probable dyshormonogenesis, 13 cases of hypoplasia and one case of left-lobe hemiagenesis. One patient had decreased volume due to central hypothyroidism. Scintigraphy scans performed 3-4 years earlier showed 100% agreement with current results. Comparisons with previous T-US showed concordant results regarding thyroid location, but a decrease in current volume was observed in eight due to the use of L-thyroxine, calling the diagnosis of hypoplasia into question. Conclusions The role of T-US goes beyond complementing scintigraphy results. It allows inferring the etiology of CH, but it must be performed in the first months of life. An accurate diagnosis of CH will be attained with molecular study and the T-US can guide this early assessment, without therapy withdrawal.

Neonatal screening: 9% of children with filter paper thyroid-stimulating hormone levels between 5 and 10µIU/mL have congenital hypothyroidism.

OBJECTIVES: To determine the prevalence of congenital hypothyroidism in children with filter-paper blood-spot TSH (b-TSH) between 5 and 10µIU/mL in the neonatal screening. METHODS: This was a retrospective study including children screened from 2003 to 2010, with b-TSH levels between 5 and 10µIU/mL, who were followed-up during the first two years of life when there was no serum TSH normalization. The diagnosis of congenital hypothyroidism was defined as serum TSH ≥10µIU/mL and start of levothyroxine treatment up to 2 years of age. RESULTS: Of the 380,741 live births, 3713 (1.04%) had filter paper TSH levels between 5 and 10µIU/mL and, of these, 339 (9.13%) had congenital hypothyroidism. Of these, 76.11% of the cases were diagnosed in the first three months of life and 7.96% between 1 and 2 years of age. CONCLUSION: The study showed that 9.13% of the children with b-TSH levels between 5 and 10µIU/mL developed hypothyroidism and that in approximately one-quarter of them, the diagnosis was confirmed only after the third month of life. Based on these findings, the authors suggest the use of a 5µIU/mL cutoff for b-TSH levels and long-term follow-up of infants whose serum TSH has not normalized to rule out congenital hypothyroidism.

Timing of thyroid ultrasonography in the etiological investigation of congenital hypothyroidism.

OBJECTIVES: To describe the findings of thyroid ultrasonography (T-US), its contribution to diagnose congenital hypothyroidism (CH) and the best time to perform it. SUBJECTS AND METHODS: Forty-four patients with CH were invited to undergo T-US and 41 accepted. Age ranged from 2 months to 45 years; 23 patients were females. All were treated with L-thyroxine; 16 had previously undergone scintigraphy and 30 had previous T-US, which were compared to current ones. RESULTS: At the current T-US, the thyroid gland was not visualized in its normal topography in 10 patients (24.5%); 31 T-US showed topic thyroid, 17 with normal or increased volume due to probable dyshormonogenesis, 13 cases of hypoplasia and one case of left-lobe hemiagenesis. One patient had decreased volume due to central hypothyroidism. Scintigraphy scans performed 3-4 years earlier showed 100% agreement with current results. Comparisons with previous T-US showed concordant results regarding thyroid location, but a decrease in current volume was observed in eight due to the use of L-thyroxine, calling the diagnosis of hypoplasia into question. CONCLUSIONS: The role of T-US goes beyond complementing scintigraphy results. It allows inferring the etiology of CH, but it must be performed in the first months of life. An accurate diagnosis of CH will be attained with molecular study and the T-US can guide this early assessment, without therapy withdrawal.

Liothyronine Improves Biochemical Control of Congenital Hypothyroidism in Patients with Central Resistance to Thyroid Hormone.

OBJECTIVE: To assess whether adding liothyronine (LT3) to levothyroxine (LT4) monotherapy normalizes serum thyrotropin (TSH) and thyroxine (T4) concentrations in children with congenital hypothyroidism and central resistance to thyroid hormone. STUDY DESIGN: We retrospectively studied 12 patients with congenital hypothyroidism and central resistance to thyroid hormone (6 treated with LT3+LT4 combined therapy and 6 treated with LT4 monotherapy). In patients receiving combined therapy, we compared serum concentrations of TSH, T4, and triiodothyronine before and after addition of LT3. We used repeated measures analysis to compare thyroid function in participants receiving combined therapy vs monotherapy, while accounting for age and intrasubject correlation. RESULTS: In patients receiving combined therapy, the addition of LT3 was associated with normalization of mean TSH (9.2 vs 4.5 mIU/L, P = .002), a lower proportion of TSH values greater than 10 mIU/L (35% vs 8%, P = .03), and a decrease in mean serum T4 by 23 ± 9% (P < .001). Compared with patients receiving LT4 monotherapy, patients receiving combined therapy had lower mean TSH (8.5 ± 0.9 vs 4.3 ± 0.4, P < .001), lower odds of TSH elevation greater than 10 mIU/L (OR 0.20, 95% CI 0.10-0.41, P < .001), and lower odds of T4 elevation (OR 0.21, 95% CI 0.04-1.09, P = .06). LT3 treatment did not increase serum T3 levels significantly. CONCLUSION: The addition of LT3 to LT4 monotherapy facilitates normalization of both serum TSH and T4 in patients with congenital hypothyroidism and central resistance to thyroid hormone. Larger prospective studies are needed to confirm these findings and to determine the effect of combined therapy on neurodevelopmental outcomes.

Thyroxine-Based Screening for Congenital Hypothyroidism in Neonates with Down Syndrome.

OBJECTIVE: To ascertain whether thyroxine (T4)-based screening programs for congenital hypothyroidism (initial measurement of total T4 [tT4] followed by thyroid stimulating hormone [TSH] measurement in patients with tT4 <10th percentile) identifies congenital hypothyroidism in all neonates with Down syndrome. STUDY DESIGN: Retrospective cohort study of 159 neonates with Down syndrome, born during the period 1998-2007 were included. Screening test results were compared with those of the general population. All primary care physicians of these infants were contacted and infants' thyroid status verified. RESULTS: tT4 concentrations in children with Down syndrome were significantly lower, and TSH higher than those in the general population; tT4 concentrations did not correlate with screening TSH concentrations. Twenty children with Down syndrome were treated with L-thyroxin within the first month of life although only 10 babies had been identified by the routine screening test. CONCLUSIONS: T4-based screening does not identify many cases of congenital hypothyroidism in neonates with Down syndrome. We recommend that neonates with Down syndrome be screened by simultaneous measurements of both tT4 and TSH.

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.