Abordagem da hiperplasia adrenal congênita pela deficiência da enzima 21-hidroxilase em crianças e adolescentes: revisão / Management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children and adolescents: review

Objetivo: Descrever o diagnóstico e manejo clínico da deficiência da 21-hidroxilase (D-21OH), no contexto atual de inclusão da doença nos programas de triagem neonatal, bem como características genéticas, fisiopatológicas e manifestações na infância e adolescência. Fonte de Dados: Revisão integrativa realizada nas bases de dados MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science nos últimos vinte anos, em língua inglesa e portuguesa; população-alvo: crianças da primeira infância à adolescência; com o uso dos termos "triagem neonatal", "hiperplasia adrenal congênita", "deficiência da 21-hidroxilase", "glucocorticoide" e "polimorfismos do gene NR3C1". Síntese de Dados: A hiperplasia adrenal congênita (HAC) constitui um grupo de doenças caracterizadas por deficiências enzimáticas na esteroidogênese do córtex adrenal. A D-21OH é responsável por 95% dos casos e, se não tratada precocemente, pode levar ao óbito no período neonatal em sua forma clássica. A triagem neonatal para a HAC consiste na dosagem do precursor 17-hidroxiprogesterona (17OHP) no sangue de recém-nascidos, permitindo rápida confirmação diagnóstica e instituição da terapêutica. A implantação da triagem neonatal constitui um avanço, mas o controle dos pacientes pediátricos com D-21OH é complexo e deve ser sempre individualizado. Conclusão: A instituição dos programas de triagem neonatal para HAC tem trazido benefícios para o prognóstico das crianças com D-21OH. Seu manejo é multiprofissional, individualizado e ainda um desafio mesmo para o especialista. Ampla divulgação do conhecimento sobre a doença é desejável para permitir melhor condução dessas crianças, especialmente de meninas com a doença que apresentam genitália atípica.

Objective: To describe the diagnosis and clinical management of 21-hydroxylase deficiency (21OH-D), in the current context of including the disease in neonatal screening programs, as well as genetic, pathophysiological characteristics, and manifestations in childhood and adolescence. Data Source: Integrative review performed in MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science databases in the last twenty years, in English and Portuguese; target population: children from early childhood to adolescence; with the use of the terms "neonatal screening"; "congenital adrenal hyperplasia"; "21-hydroxylase deficiency"; "glucocorticoid"; "polymorphisms of the NR3C1 gene". Data Synthesis: Congenital adrenal hyperplasia (CAH) is a group of diseases characterized by enzyme deficiencies in adrenal cortex steroidogenesis. 21OH-D is responsible for 95% of cases and, if not treated early, can lead to death in the neonatal period in its classic form. Neonatal screening for CAH consists of measuring the precursor 17-hydroxyprogesterone (17OHP) in the blood of newborns, allowing rapid diagnostic confirmation and institution of therapy. The implementation of neonatal screening is an advance, but the control of pediatric patients with 21OH-D is complex and must always be individualized. Conclusion: The institution of newborn screening programs for CAH has benefits for the prognosis of children with 21OH-D. Its management is multi-professional, individualized and still a challenge even for the specialist. Wide dissemination of knowledge about the disease is desirable to allow better management of these children, especially girls with the disease who have atypical genitalia.

Effect of treatment on growth in congenital adrenal hyperplasia.

In 22 patients with congenital adrenal hyperplasia (CAH), the effect of treatment on growth was evaluated retrospectively. The degree of control with treatment had generally been assessed by measurements of serum 17-hydroxyprogesterone (17-OHP) and/or urinary pregnanetriol levels. In 20 patients, there were no significant differences in both height SDS for bone age (-2.05 +/- 1.89 vs -1.85 +/- 1.30) and height SDS for chronological age (CA) (0.23 +/- 1.94 vs -0.36 +/- 1.81) in a mean uninterrupted treatment period of 5.80 +/- 3.58 years. Further analysis in salt-losers and nonsalt-losers separately showed that height SDS for bone age had decreased in the salt-losers and had increased in the nonsalt-losers. Six patients had signs of early puberty. In 22 patients, there was a negative correlation between the prednisolone dose on one hand and height velocity SDS for CA and bone age velocity on the other. It was also found that the mean serum levels of 17-OHP did not always reflect the degree of long term control measured by auxological parameters. These findings indicate that our treatment in the patients did not result in a significant improvement in height prognosis. We can conclude that growth prognosis in CAH patients can be improved by relying on auxological parameters rather than serum 17-OHP and urinary pregnanetriol levels for monitoring control. Special attention should be paid to salt-losers in this respect.

Medición de 17-OH progesterona sanguínea en recién nacidos chilenos: antecedentes para implementar un programa de detección neonatal de hiperplasia suprarrenal congénita / 17 OH progesterone measurement in blood of chilean newborns: as a background to start a congenital adrenal hyperplasia screening program

Background: The early diagnosis and therapy of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can prevent adrenal crises and erroneous gender assignment in affected newborns. To achieve this goal neonatal mass-screening programs have been developed, measuring blood 17 alpha-hydroxyprogesterone (17OHP). In Chile there is no experience with this type of screening. Aim: To develop a method for measuring 17OHP in filter paper blood specimens. To obtain reference ranges and determine neonatal 17OHP threshold levels according to gestational age and birth weight. To analyze factors affecting the cost-efficiency ratio and suggest recommendations for the organization of a neonatal screening program for CAH in Chile. Material and methods: Nine hundred twenty two newborns were studied. 17OHP was measured using double antibody radioimmunoassay in filter paper blood samples obtained 48 h after birth. Reference ranges were determined according to gestational age and birth weight and a cutoff point of 25 ng/ml was established. Results: Seventeen newborns had 17OHP over the cutoff value. They were assessed by a pediatric endocrinologist and in none of them, CAH was confirmed. Therefore the false positive rate of the determination was 1.8 percent. Among these newborns with elevated 17OHP, 66 percent had a birth weight below 1.5 kg and 5.8 percent, a birth weight between 1.5 and 2.5 kg. The cost per reported result was US $ l. Timing of the recall was between the 3 and 10 days of life. No newborn missed the follow-up. Discussion: To increase the cost-efficiency ratio of an eventual neonatal screening program, newborns with birth weights below 1.5 kg should be excluded and cutoff points should be defined according to birth weight