Determinación de valores de corte de 17 hidroxiprogesterona ajustados por edad gestacional para la pesquisa neonatal de la hiperplasia suprarrenal congénita / Assessment of gestational age-adjusted 17-hydroxyprogesterone cut-off values for neonatal screening of congenital adrenal hyperplasia

La pesquisa neonatal de hiperplasia suprarrenal congénita se realiza mediante la determinación de 17 hidroxiprogesterona (17OHP) en gotas de sangre seca en papel de filtro. Los bebés prematuros presentan valores más elevados que los bebés de término, siendo de utilidad contar con límites de corte apropiados. Nuestro objetivo fue actualizar los valores de corte de 17OHP ajustados por edad gestacional para la metodología en uso a nivel nacional por las jurisdicciones asistidas por el "Programa Nacional de Fortalecimiento de la Detección Precoz de Enfermedades Congénitas". La 17OHP se determinó utilizando el kit comercial de enzimo-inmunoanálisis (ELISA competitivo), Elizen Neonatal 17OHP Screening (Zentech, Bélgica). Se obtuvieron límites de corte utilizando percentiles de la distribución de los valores de 17OHP para cada edad gestacional. La sensibilidad obtenida fue 100%, especificidad 98,76 %, tasa de falsos positivos 1,24 % y el valor predictivo positivo 1,12 %. Destacamos la importancia de disponer de límites de corte adecuados a la población. La armonización de los mismos permitirá resultados comparables entre los programas regionales de pesquisa neonatal (AU)

Newborn screening for congenital adrenal hyperplasia is performed by the measurement of 17-hydroxyprogesterone (17OHP) in dried blood spots on filter paper. Premature infants have higher values than full-term infants, and appropriate cutoff values are useful. Our aim was to update the cut-off values of 17OHP adjusted for gestational age for the methodology used at a national level in regions assisted by the "National Program for Strengthening the Early Detection of Congenital Diseases". 17OHP was determined using the commercial enzyme-linked immunosorbent assay (competitive ELISA) kit, Elizen Newborn 17OHP Screening (Zentech, Belgium). Cut-off values were obtained using percentiles of the distribution of 17OHP values for each gestational age. Sensitivity was 100%, specificity 98.76%, false positive rate 1.24%, and positive predictive value 1.12%. It is important to have cut-off values that are adjusted to the population. Harmonization will allow for the comparison of results among regional newborn screening programs (AU)

Carcinoma diferenciado de tiroides (CDT) en niños y adolescentes: Evolución clínica y factores pronósticos / Differentiated thyroid carcinoma in children and adolescents: Clinial outcome and prognostic factors

Si bien la forma de presentación del CDT es más agresiva en la edad pediátrica que en los adultos, la tasa de sobrevida es superior al 90%.Objetivo: analizar retrospectivamente las características clínico-patológicas,la evolución y los factores pronósticos en pacientes prepuberales (PP) y puberales (P) con diagnostico de CDT controlados en nuestro servicio. Resultados se incluyeron 43 pacientes seguidos por un tiempo X (±DS) de 5.99 años(a) (3.57) a, rango 1 -14 a. El tratamiento consistió en tiroidectomía con vaciamiento ganglionar, Iodo131 y levotiroxina en dosis inhibitoria de TSH. Al diagnóstico: edad cronológica (EC) X (±DS)10.9 (3.84) a, rango: 4.7 -17a, relación femenino /masculino 2.9. Diecinueve PP y 24 P. El 53.5% (n:23) presentó nódulos confinados a la glándula con o sin extensión ganglionar y el 46.5% (n:20) tenia un estadío tumoral más avanzado con invasión local y metástasis (MTS) pulmonar. Treinta y ocho pacientes (88.4%) tenían MTS ganglionar cervical y 16(37.2%) MTS pulmonar. El grupo PP comparado con el P tenía EC significativamente menor X (±DS) 7.25 (2.03) a vs 13.83a (p <0.001), estadío tumoral más avanzado 84.2 vs16.8% (p<0.001) y mayor ocurrencia de MTS pulmonar 68.4 vs 12.5% (p<0.003). La sobrevida global fue de 92% y libre de enfermedad 78%.Las variables predictoras de persistencia de enfermedad más significativas fueron presencia de MTS pulmonar al diagnóstico y niveles séricos de tiroglobulina superiores a 8.5 ng/ml posterior al tratamiento inicial. Conclusión: el CDT pediátrico tiene una presentación agresiva especialmente en los pacientes prepuberales. El pediatra debería incorporar el examen clínico del cuello para realizar un diagnóstico y tratamiento precoz (AU)

Children-DTC has been found to behave differently than in adults. At diagnosis, children present in a more aggressive way. However the overall survival rates is greater than 90%. The aim of this study was to perform a retrospective analysis of clinicopathologycal features at diagnosis, evolution and prognostic factors for DTC in pre-pubertal (PP)and pubertal (P)children treated at our centre. Results: 43 CDT patients were included. Mean follow up was X (±DS) 5.99 (3.57) years (y) range: 1 -14 y. Treatment consisted on total thyroidectomy with lymph node dissection, radioiodine therapy, and TSH suppressive therapy with L-thyroxine. At diagnosis: chronological age (CA) was (±DS) :10.9 (3.84) y, range: 4.7 - 17y,sex: female/male ratio: 32/11,nineteen were PP and 24 P. Twentythree ( 53.5%) presented intrathyroidal nodes with or without lymph node MTS, Twenty patients (46.5%) had advanced disease, with adjacent tissue invasion and lung MTS. Thirty-eight patients (88.4%) had cervical lymph node MTS, 16 (37.2%) lung MTS.PP group had significant less CA X (±DS) 7.25 (2.03) y vs 13.83 (1.95)y (p <0.001),advanced tumor stage 84.2 vs16.8% (p<0.001) and more lung MTS occurrence 68.4 vs 12.5% (p<0.003). Global survival rate was 92% and disease free survival rate was 78%.Lung metastases (MTS) and serum thyroglobuline levels greater than 8.5 ng\ml post initial treatment were the most significant prognostic factor related to persistent disease. Conclusion: CDT had a more aggressive presentation in children; especially in PP children. Pediatricians should be aware of this in order to realize a precocious diagnosis and treatment (AU)

Unexpected peripheral markers of thyroid function in a patient with a novel mutation of the MCT8 thyroid hormone transporter gene.

The specific thyroid hormone transporter, MCT8, located on the X chromosome, has led to the identification a novel syndrome. The objective is to relate phenotype with several tissue-specific thyroid functions. A 1-year-old boy, who had severe psychological damage and low serum T4, had received l-T4 for 3 months. At admission, body length was normal but weight was low. Off therapy, serum TSH was mildly elevated, serum T4 and free T4 were low, and serum T3 and free T3 were high. Direct sequencing of the MCT8 gene revealed a single nucleotide change that resulted in a novel nonsense mutation at codon 261 (Q261X) in exon 3. Since serum T3 was high, peripheral markers of hyperthyroidism were looked for. Bone age was advanced, despite the presence of malnutrition and low T4. Serum SHBG, a marker of thyroid hormone action in liver, was markedly elevated. Markers of skeletal muscle catabolism, ammonemia and lactic acid, were found to be elevated. The phenotype of MCT 8 mutation might be explained by differences in the entry of thyroid hormones into different cells. In the presence of an inactive MCT8 transporter, the high blood T3 levels might not be enough to prevent brain damage early in life, while they seem to be able to induce a postnatal state of peripheral hyperthyroidism in other tissues, such as liver, bone and skeletal muscle.