Laboratorio de función tiroidea en pediatría. Ventajas y limitaciones de los métodos indirectos para la obtención de intervalos de referencia / Thyroid function laboratory in pediatrics. Advantages and limitations of indirect methods to obtain reference intervals

Obtener intervalos de referencia (IRs) confiables para pruebas de laboratorio en pediatría es particularmente complejo y costoso. Una alternativa a este problema es el uso de métodos indirectos, donde se usan grandes bases de datos preexistentes de pacientes. Nuestros objetivos fueron: calcular IR para TSH y hormonas tiroideas (Perfil tiroideo, PT) en población pediátrica que asiste al Hospital de Pediatría Juan P. Garrahan, por método indirecto y verificar la confiabilidad de los mismos para su aplicación. Se recolectaron datos de 19.842 pacientes entre enero de 2020 y diciembre de 2021. Se aplicaron filtros para eliminar los pacientes que pudieran tener afectado el PT. Los 4.861 pacientes incorporados al análisis fueron divididos en 3 grupos: G1: 0-12 meses (n: 551), G2:13 meses- 7 años (n: 1347) y G3: 8 -18 años (n: 2963). Los IR fueron calculados por 2 métodos: el de Hoffman adaptado y el de CLSI EP28A3, para cada grupo de edad. TSH, TT3 y T4L se analizaron con Architect i4000-Abbott y TT4 con Immulite 2000XPi-Siemens. Para la primera etapa de verificación se utilizaron 20 sueros de pacientes provenientes de análisis prequirúrgicos. Los outliers se detectaron aplicando el método de Tukey. Los datos fueron procesados según CLSI EP28A3c. Los IR obtenidos fueron similares a los previamente publicados obtenidos por método directo. Los resultados de la verificación fueron en su mayoría aceptados. Por lo tanto, los métodos indirectos son una buena alternativa de cálculo de IR en pediatría (AU)

Obtaining reliable reference ranges (RRs) for laboratory tests in pediatrics is particularly complex and costly. An alternative to this problem is to use of indirect methods, where large pre-existing patient databases are used. Our aims were to calculate RRs for TSH and thyroid hormones (thyroid profile, PT) in children seen at Hospital de Pediatría Juan P. Garrahan by indirect methods and to verify their reliability for their application. Data were collected from 19,842 patients seen between January 2020 and December 2021. Filters were applied to eliminate patients in whom the PT was potentially affected. The remaining 4,861 patients included in the analysis were divided into 3 groups: G1: 0-12 months (n: 551), G2: 13 months-7 years (n: 1347) and G3: 8-18 years (n: 2963). RRs were calculated by 2 methods: the adapted Hoffman method and the CLSI EP28A3 method, for each age group. TSH, TT3, and FT4 were analyzed with Architect i4000-Abbott and TT4 with Immulite 2000XPi-Siemens. For the first stage of verification, 20 patient sera from pre-surgical analysis were used. Outliers were detected by applying the Tukey method. The data were processed according to CLSI EP28A3c. The RRs obtained were similar to those previously published using the direct method. The verification results were mostly acceptable. Therefore, indirect methods are a good option for calculating RRs in children (AU)

Diagnosis and management of Intratyroid Ectopic Thymus. / Diagnóstico y manejo del Timo Ectópico Intratiroideo.

INTRODUCTION: Intrathyroidal ectopic thymus (IET) is a rare benign condition caused by the aberrant thymic migra tion during embryogenesis. It is usually incidentally diagnosed as a thyroid nodule. OBJECTIVE: To report the intrathyroidal location of ectopic thymic tissue and to describe the ultrasound findings in children. PATIENTS AND METHOD: Retrospective descriptive review of the medical charts and thyroid ultrasound studies of children with nodular images in the thyroid gland, in a third level national pediatric hospital, from January 2010 to August 2017. Solid hypoecogenic intrathyroid lesions with multiple linear tracts or hyperechogenic points that did not change their characteristics during fo llow-up were considered intrathyroidal thymos. The ultrasound follow-up was performed every 4-6 months. The ultrasound characteristics of the lesions (location, laterality, size and shape), the indi cation of the ultrasound scan and the follow-up time were analyzed. RESULTS: Of 147 patients with thyroid nodules, we identified 12 children with lesions suggestive of an IET (8.1%). The mean age at diagnosis was 3.9 years (range 0-8). It was an incidental finding in all cases. Imaging findings were unilateral in eight patients and bilateral in four patients. All lesions were located in the mid and/or posterior portion of the gland. We adopted a watch-and-wait approach with ultrasound follow-up (mean 2.2 years; range 0.83-4) in all patients except in a 7-year-old boy who presented uncertain findings and underwent surgery, confirming IET in the pathological study. CONCLUSIONS: Thymic inclu sions in the thyroid gland are a rare but increasingly frequent finding, possibly related to the increased use of ultrasound studies. Pediatricians and radiologists should be aware of this entity to differentiate it from other thyroid lesions, avoiding unnecessary studies and/or treatments in these patients.

Evaluación de sensibilidad-especificidad de valores de 170H progesterona sérica, basales y post estímulo con ACTH, en función del análisis molecular del gen CYP21A2 en la deficiencia de 21-hidroxilasa no clásica / Evaluation of sensitivity and specificity of serum 170H progesterone values at baseline and post ACTH stimulation in the function of molecular analysis of the CYP21A2 gene in non-classic 21-hydroxilase deficiency

La forma no clásica, post natal, de la hiperplasia suprarrenal congénita tiene una incidencia de 1 en 1000 en la población general y afecta al 6% de las mujeres hirsutas. En este estudio se estableció la sensibilidad y la especificidad de la respuesta de los niveles séricos de 17-hidroxiprogesterona (17OHP4) al estímulo agudo con ACTH en 203 pacientes de ambos sexos, pre y post puberales, con hiperandrogenismo, en los cuales se analizó si tenían una alteración molecular del gen CYP21A2. Posteriormente al estudio molecular, los pacientes fueron clasificados en tres grupos de acuerdo al genotipo: Gr0, n=61: ningún alelo mutado (no portadores de mutación); Gr1, n=55: un alelo mutado (portadores) y Gr2, n=87: dos alelos mutados (afectados). Por análisis de regresión logística (curvas ROC) se compararon los valores basales del Gr2 vs Gr0 y se obtuvo un valor de 17OHP4 de 7,2 ng/ml con una sensibilidad del 83% y una especificidad del 85%. Se sugiere entonces que en los pacientes con este nivel basal no se debería realizar el test de ACTH, y habría que confirmar el diagnóstico con el estudio molecular. Los niveles 17OHP4 a los 60 minutos post estímulo con ACTH mayores a 20 ng/ml son confirmatorios del diagnóstico con 84% de sensibilidad y 88% de especificidad. No sería necesario entonces realizar estudios moleculares. Un valor de 15,6 ng/ml diferencia Gr2 de Gr0 con una sensibilidad del 89% y una especificidad del 95%. Este es un buen valor predictivo, pero el análisis molecular no debería obviarse en aquellos casos en los que exista una fuerte sospecha clínica. (AU)

The incidence of non classic congenital adrenal hyperplasia is 1:1000 in the general population and it is present in 6% of hirsute women. In this study, the sensitivity and specificity of serum 17-hydroxyprogesterone (17OHP4) response to acute ACTH stimulation was evaluated in 203 prepubertal and pubertal patients of the two sexes with hyperandrogenism, in whom the CYP21A2 gene was analyzed. After molecular analysis patients were divided in 3 groups according to genotype: Gr0, n=61, no mutated allele (no mutation carrier); Gr1, n=55, one mutated allele (carrier); and Gr2, n=81, two mutated alleles (affected patient). Using logistic regression analysis (ROC curves), basal values in Gr2 vs. Gr0 were compared and a cutoff value of 7.2 ng/ml was defined to separate groups, with 83% sensitivity and 85% specificity. It is suggested then that in patients with levels higher than 7,2 no ACTH test is necessary and molecular analysis is required to confirm diagnosis. Serum 17OHP4 values above 20 ng/ml 60 minutes after ACTH are confirmatory of diagnosis, with 84% sensitivity and 88% specificity. No molecular studies should be necessary. A 15.6 ng/ml cutoff value is able to differentiate Gr2 from Gr0, with 89% sensitivity and 95% specificity. It is a good predictive value, but carrying out molecular analysis is only advisable if clinical evidence is strong (AU)