Background: Neonatal screening for congenital hypothyroidism (CH) in premature infants is not as well established as in term newborns regarding age and number of samples. Aims: 1. To evaluate the effectiveness of the protocol recommended by the Neonatal Screening Program of the State of Minas Gerais (PETN-MG) for CH neonatal screening in very low birth weight premature infants. 2. To estimate the prevalence of delayed TSH elevation and thyroid function alterations in the target population. Methods: TSH was assessed by ELISA on the 5 th , 10 th and 30 th days of life in all newborns with gestational age <32 weeks and/or very low birth weight (VLB) (<1,500 g) in the period from October 2004 to September 2006. Results: Out of the 14,462 newborns screened, 2,647 were premature with gestational age <32 weeks and/or VLB. Forty-four cases of altered TSH were found and 11 infants underwent treatment. Delayed TSH elevation was detected in 66% of altered cases. Five out of the 11 cases were detected in the second sample and five cases were only detected in the third sample. Conclusion:The high prevalence of thyroid function alterations that demanded treatment (1:242) and delayed TSH elevation in VLB premature infants reinforce the need for a specific protocol, based on retesting procedures, for CH neonatal screening. KEY WORDScongenital hypothyroidism, premature newborn, neonatal screening, very low birth weight VOLUME 23, NO. 1-2,2010 45 Brought to you by |

The etiology of Congenital Hypothyroidism (CH) is important in determining its severity, prognosis, genetic counseling and clinical management. Aims: investigate the causes of CH and their severity using serum levels of FreeT4 and TSH. Patients and Methods: 243 neonates with CH (61% were girls) diagnosed by the Neonatal Screening Program of Minas Gerais between 1996 and 2003. The thyroid function was assessed through serum FreeT4 and TSH by chemilumiscence. CH etiology was evaluated by ultrasonography, scintigraphy, potassium perchlorate discharge test and serum thyroglobulin levels. Results: Out of 243 patients, dysgenesis was found in 114 (47%): 3.3% had athyreosis; 0.4% eutopic dysgenetic gland due to maternal use of 131 I; 22% ectopic glands (8.6% an isolated ectopic gland and 13% also an eutopic dysgenetic thyroid); 9% eutopic dysgenesis, 8.6% hypoplasia and 3.7% hemiagenesis. Thyroid in situ was found in 129 (52%): 23.5% had iodide organification defect; 3.7% thyroglobulin synthesis defect; 6.2% other dyshomonogenesis; 0.4% iodide transport defect; 1.2% transient CH and 18% a normal gland. Patients with dysgenesis had a more severe CH than those with thyroid in situ (TSH 248.08 vs. 18.17 µIU/mL and FT4 0.32 vs. 0.95 ng/dL, p<0.001). Conclusions: Some cases had more complex dysgenesis, presenting ectopia associated to a dysgenetic eutopic gland. The ultrasound was the best tool to detect the dysgenetic tissue, but

RESUMOO 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% 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 583,4µUI/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. Early diagnosis and treatment of congenital hypothyroidism are the main goals of the neonatal screening programs. A retrospective analysis was carried out to assess the characteristics and etiologies of congenital transient hypothyroidism (CTH) in the Newborn Screening Program of the State of Minas Gerais, Brazil. To reach a diagnosis of CTH, altered screening and serum confirmatory T4 and TSH tests and normal serum free T4 and TSH at 4 and 8 weeks after the withdrawal of levothyroxine were used. We studied 21 children with CTH who represented 4.23% of the whole group with detected hypothyroidism and followed them up in the Screening Program. These patients received LT4 therapy for a variable period of one month to three years. Serum confirmatory TSH levels varied from 10.4 to 583.4µUI/mL. Maternal antibodies, TRAB and anti-TPO, were associated to CTH in two children and iodine overload in one of them. We concluded that CTH is an important component in neonatal screening and hormonal treatment during the first months of the life is essential. The TSH initial levels are not relevant to determine whether the thyroid dysfunction is transient or permanent.

Objective: The purpose of this study was to identify factors that might interfere with reaching the final height in patients with 21-hydroxylase deficiency (21-OHD). Subjects and methods: Thirty-one patients with classical 21-OHD who reached their FH in our Institution were evaluated in order to compare the Z score for final height (FHZ) with: (1) the target height, (2) the standard height for the population, and (3) the hydrocortisone treatment schedule. Results: The FHZ of -2.13 ± 1.11 had a significant negative correlation with the hydrocortisone doses used throughout the period of study. Patients who reached FH within the normal population range were those who received lower doses of hydrocortisone, as compared to those whose FH remained below -2 SDS. Conclusion: We conclude that careful treatment adjustments have a major influence on growth of children with CAH, and that the dose range for hydrocortisone replacement that does not lead to side effects is relatively narrow. The better height outcome was achieved in 21-OHD patients who received lower doses of hydrocortisone. Arq Bras Endocrinol Metab. 2013;57(2):126-31 Keywords Congenital adrenal hyperplasia; steroid 21-hydroxylase; corticosteroids; hydrocortisone; body height RESUMO Objetivo: O objetivo do estudo foi a identificação de fatores que podem interferir na aquisição de altura final de pacientes com a deficiência de 21-hidroxilase (21OHD). Sujeitos e métodos: A altura final (escore Z: FHZ) de 31 pacientes com a forma clássica da 21OHD, acompanhados em nossa instituição, foi comparada com: (1) a altura alvo, (2) o padrão de referência para a população, e (3) a dose de hidrocortisona durante o acompanhamento. Resultados: Observou-se correlação negativa significativa entre o FHZ de -2,13 ± 1,11 e as doses de hidrocortisona utilizadas durante o período de estudo. Os pacientes que atingiram altura final dentro do padrão de referência para a população usaram doses mais baixas de hidrocortisona quando comparados àqueles que permaneceram abaixo de -2 DP. Conclusão: O cuidado nos ajustes das doses durante o tratamento da 21OHD tem grande influência sobre o crescimento das crianças. A faixa de variação da dose de reposição da hidrocortisona que não causa efeitos colaterais é relativamente estreita. O melhor resultado estatural foi observado nos pacientes com 21OHD tratados com doses mais baixas de hidrocortisona. Arq Bras Endocrinol Metab. 2013;57(2):126-31 Descritores

SUMMARYThe aim of this study was to identify the genetic defect of a patient with dyshormonogenetic congenital hypothyroidisms (CH) with total iodide organification defect (TIOD). A male child diagnosed with CH during neonatal screening. Laboratory tests confirmed the permanent and severe CH with TIOD (99% perchlorate release). The coding sequence of TPO, DUOX2, and DUOXA2 genes and 2957 base pairs (bp) of the TPO promoter were sequenced. Molecular analysis of patient's DNA identified the heterozygous duplication GGCC (c.1186_1187insGGCC) in exon 8 of the TPO gene. No additional mutation was detected either in the TPO gene, TPO promoter, DUOX2 or DUOXA2 genes. We have described a patient with a clear TIOD causing severe goitrous CH due to a monoallelic TPO mutation. A plausible explanation for the association between an autosomal recessive disorder with a single TPO-mutated allele is the presence of monoallelic TPO expression. Arq Bras Endocrinol Metab. 2010;54(8):732-7 SUMÁRIO O objetivo deste estudo foi identificar defeitos genéticos em paciente com hipotireoidismo congênito (HC) por disormonogênese e defeito total de incorporação de iodeto (DIIT). Neonato do sexo masculino com HC diagnosticado pelo rastreamento neonatal. Exames clínicos e radiológicos confirmaram que o paciente apresentava HC severo e permanente com DIIT (teste de perclorato: 99%). A região codificadora dos genes TPO, DUOX2, DUOXA2 e 2957 pares de bases (pb) do promotor de TPO foram sequenciados. No paciente foi identificada a duplicação em heterozigose GGCC no éxon 8 do gene TPO (c.1186_1187insGGCC). Nenhuma outra mutação foi localizada nos genes TPO, incluindo o promotor, DUOX2 ou DUOXA2. Descrevemos paciente com grave defeito de organificação de iodeto, provocando HC severo com bócio, em consequência de uma única mutação monoalélica no gene TPO. A expressão monoalélica no tecido tireoideano explicaria a associação de uma doen ça autossômica recessiva com uma única mutação monoalélica. Arq Bras Endocrinol Metab. 2010;54(8):732-7