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

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.

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.

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.

Hipotiroidismo congénito secundario a hipoplasia tiroidea detectado en edad adulta / Congenital hypothyroidism secondary to thyroid hypoplasia detected in adulthood

La ubicación anatómica de la glándula tiroidea y su biosíntesis hormonal están reguladas por la expresión de ciertos genes, cuya alteración puede conducir a las denominadas disgenesias tiroideas: agenesia, ectopía e hipoplasia, así como a las variantes dishormonogenéticas. Se presenta el caso de una paciente con retraso mental y diagnóstico de hipotiroidismo realizado en la edad adulta. Las determinaciones bioquímicas confirmaron el diagnóstico de hipotiroidismo no autoinmune. Este caso representa la evolución prolongada de una hipofunción tiroidea, que cursó en forma solapada y no diagnosticada durante 53 años de vida, con secuelas relevantes de esta deficiencia al momento del diagnóstico. La terapia exógena logró mejorías evidentes en la signo sintomatología, pero no revirtió el presunto daño neurológico atribuible a la falta de hormona tiroidea necesaria durante el desarrollo fetal. En la necropsia realizada se encontró escaso tejido tiroideo cervical correspondiente a hipoplasia tiroidea eutópica. El hallazgo de un remanente tiroideo menor a 1 cm permite explicar la supervivencia de la paciente hasta una edad avanzada.

The anatomical location of the thyroid gland and its hormone byosinthesis are regulated by the expression of certain genes, whose disruption leads to the so-called thyroid dysgenesis: agenesis, ectopia and hypoplasia, and to dyshormonogenesis. We present the case of a patient with mental retardation and hypothyroidism whose diagnosis was made in adulthood. Biochemical determinations confirmed the diagnosis without evidence of thyroid autoimmunity. This patient represents the extended evolution of a thyroid hypofunction, which lasted in an unsuspected way for 53 years, with important consequences of this deficiency at diagnosis. Exogenous therapy achieved great improvement in clinical symptoms, but did not reverse the neurological damage attributable to the lack of thyroid hormone necessary for fetal development. The necropsy revealed little thyroid tissue in the neck corresponding to eutopic thyroid hypoplasia. The discovery of a remaining thyroid of less than 1 cm justified the patient survival up to old age.

Hipotireoidismo congênito: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia / Congenital hypothyroidism: recommendations of the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism

O hipotireoidismo congênito (HC) é o distúrbio endócrino congênito mais frequente, com incidência variando de 1:2.000 a 1:4.000 crianças nascidas vivas e uma das principais causas de retardo mental que pode ser prevenida. Os Programas de Triagem Neonatal para a doença permitem a identificação precoce dos afetados e seu tratamento de modo a evitar as complicações da falta do hormônio. A maioria dos casos de hipotireoidismo congênito é decorrente de disgenesias tireoidianas (85%), entre elas a ectopia, hipoplasia ou agenesia tireoidianas, e os demais resultam de defeitos de síntese hormonal. As crianças afetadas (> 95%) geralmente não apresentam sintomas sugestivos da doença ao nascimento. Os sintomas e sinais mais comuns são: icterícia neonatal prolongada, choro rouco, letargia, movimentos lentos, constipação, macroglossia, hérnia umbilical, fontanelas amplas, hipotonia e pele seca. Várias estratégias são utilizadas para a triagem do HC. No Brasil, esta é obrigatória por lei e geralmente é feita com a dosagem de TSH em sangue seco coletado do calcanhar. A idade recomendada para sua realização é após as 48 horas de vida até o quarto dia. A confirmação diagnóstica é obrigatória com as dosagens de TSH e T4 livre ou T4 total.

Congenital hypothyroidism (CH) is the most common congenital endocrine disorder, with an incidence of 1:2,000 to 1:4,000 live births and it is a leading preventable mental retardation. Neonatal Screening Programs allow early identification of the disease and the adequate treatment of affected children can avoid the complications related to deprivation of the hormone. Most cases of primary congenital hypothyroidism (85%) are due to thyroid dysgenesis (ectopia, hypoplasia or agenesis) while the remaining result from defects in hormone synthesis. Affected children (> 95%) usually have no symptoms suggesting the disease at birth. The most frequent symptoms and signs are prolonged neonatal jaundice, hoarse cry, lethargy, slow movements, constipation, macroglossia, umbilical hernia, large fontanelle, hypotonia and dry skin. Around the world, various strategies are used for the screening of the CH. In Brazil, screening for CH is mandatory by law and usually done by serum TSH in dried blood collected from the heel. The recommended age for performing this test is after 48 hours of life until the 4th day. Diagnostic confirmation is required dosing TSH and free T4 or total T4 in serum.

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.

[Congenital hypothyroidism: about 5 observations]

Congenital hypothyroidism is one of the most frequent endocrine disease in childhood and its consequences are potentially harmful on the neurological and intellectual development of the child. We report the following 5 cases to underline the rarity of certain aetiologies and importance of an early management. Our first case involves a brother and a sister coming from Ouezzane [endemic zone], who presented at the age of 20 with an enormous goitre and cretinism. The second case is about two brothers and one sister coming from Sale [a non endemic area], with consanguineous parents. The first case was discovered at birth because of a neonatal goiter. The diagnosis in the second and third siblings was made when they were around 2 years of age because of a goitre and signs of hypothyroidism. Hormonal substitution was prescribed with a good physical and psychomotor evolution. If iodine deficiency remains the most frequent aetiology, other causes such as hormonogenesis disorders must be considered in non endemic area. In our countiy, systematic screening for congenital hypothyroidism during the neonate period, as well as an early treatment will make it possible to improve the physical and psychomotor prognosis of congenital hypothyroidism

Hipotiroidismo neonatal: fisiopatogenia, aspectos moleculares, metabólicos y clínicos / Neonatal hypothyroidism: Pathophysiogenic, molecular and clinical aspects

This review provides an updated summary on both the clinical and diagnostic aspects of neonatal hypothyroidism (NeH); as well as on the molecular and pathophysiologic processes known to be involved in the installment of this important hormonal deficiency. Current information regarding its etiology and pathogenesis has allowed classigying NeH in three major groups: endemic, transient, and sporadic hypothyroidism. The later corresponds to congenital hypothyroidism and encompasses a broad spectrum of hereditary disorders causing hypothyroidism in newborns and young children. These congenital disorders include hypothalamic-pituitary or thyroid dysgenesis and/or dyshormonogenesis, as well as hyporesponsiveness or resistance to either TRH, TSH or to thyroid hormones. The introduction of national screening programs for NeH have overcome the difficulties in the early diagnosis thus helping to prevent its serious and irreversible consequences on intellectual and physical development. Concomitantly, an increase in the need for complementary etiologic and molecular diagnosis has risen. The current capability to perform a fine and precise diagnose is crucial both for treatment of the affected infant and for genetic counseling of the family. Although incomplete, available epidemiological information in Mexico indicates that NeH prevalence can be as high as twice that in other developed world countries. On these bases, national public health policies and epidemiological surveyance must be strengthen not only to identify, diagnose and timely treat, but to prevent and eradicate endemic NeH.

Este trabajo revisa algunos aspectos del conocimiento actual sobre la fisiopatogenia, los hallazgos clínicos y el diagnóstico bioquímico y molecular del hipotiroidismo neonatal (HNe). El término HNe denota un conjunto de entidades clínicamente pleomórficas, que invariablemente cursan con una disminución en el aporte; o bien, en la disponibilidad celular y/o en la respuesta a las hormonas tiroideas (HT) durante la etapa perinatal. Las HT o yodotironinas son indispensables para la morfogénesis y maduración funcional normal de prácticamente todos los tejidos en el organismo, y su participación es crucial en el caso del sistema nervioso. La información actual permite realizar una clasificación del HNe tanto en términos etio y fisiopatogénicos, como en el contexto del substrato genético que los determina. Así, se reconocen tres grandes tipos de HNe: el endémico, el transitorio y el esporádico. Este último grupo de HNe incluye los defectos hipotálamo-hipofisiarios, los trastornos ontogenéticos o disgenesias tiroideas, la resistencia periférica a las HT y las dishormonogénesis. Por otra parte, en la comunidad internacional existe una creciente preocupación por la contaminación ambiental debida a órgano-halógenos antropogénicos. Estos compuestos han mostrado su potencial como agentes distiroideos en animales de experimentación y en algunos estudios clínicos. En México, tanto la distribución geográfica y prevalencia del HNe, como la deficiencia de yodo y otros micronutrimentos en la dieta, se han analizado de manera esporádica y no sistemática. Aunque incompleta, la información disponible sugiere que en nuestro país la prevalencia de HNe es sensiblemente mayor que la reportada mundialmente. Contar con información completa y confiable acerca de estos aspectos no es trivial, puesto que su conocimiento permitirá establecer políticas razonadas de salud pública para identificar, diagnosticar y tratar oportunamente el padecimiento; así como para prevenir y erradicar el HNe endémico.

high prevalence of severe congenital hypothyroidism: a necessity for an effective strategy of detection and treatment in the national screening program for neonatal hypothyroidism

The high prevalence of congenital hypothyroidism [CH] has been reported previously, however the severity of CH has not been evaluated yet. This report illustrates the severity of CH in Tehran and Damavand.From February 1998 to May 2003, 31 hypothyroid neonates [>37 weeks gestation] were detected during the CH screening program in Tehran and Damavand. Neonates were grouped in permanent [n=25] and transient CH [n=6]. Those in the permanent CH were assigned in Dysgenetic [n=18] and dyshormonogenetic [n=5] groups. Dysgenetic cases were further classified in ectopic-hypoplastic [n=13] and athyroitic [n=5] cases. Serum thyroxine values and frequency distribution of sever hypothyroidism [T4<42.8nmol/L] were compared among the groups.Mean [ +/- SD] of T4 of permanent CH [38.0 +/- 42.2 nmol/l] was significantly lower than transient CH [101.9 +/- 46.5 nmol/l] [p < 0.01]. It was similar in dysgenetic [41.9 +/- 47.5 nmol/l] and dyshormonogenetic [27.8 +/- 23.7 nmol/l]. Both latter groups shoed significantly lower T4 values than transient CH [p < 0.05]. Athyreotic cases [11.1 +/- 5.9 nmol/l] had lower T4 levels than transient CH [p < 0.05]. Severe CH was present in 18[72%] permanent, 1[16.7%] transient, 8[61.5%] ectopic-hypoplastic, 5[100%] athyroitic, and 5[71.4%] dyshormonogenetic CH cases. Odds ratio of severe CH occurrence in permanent CH as compared to transient CH was 12.9[95% CI: 1.27-130.54].The high prevalence of severe CH warrants an effective national CH screening program for early detection of CH cases and sufficient replacement therapy