Hiperplasia adrenal congênita: dosagem da 17-hidroxiprogesterona basal para seleção e casos para realização do teste de estímulo com ACTH sintético Translated title: Congenital adrenal hyperplasia: measurement of basal 17-hydroxyprogesterone as a screening test to select patients for the synthetic ACTH provocative test

Abstract

OBJETIVOS: avaliar se os níveis de 17-hidroxiprogesterona podem predizer o resultado do teste de estímulo como diagnóstico de hiperplasia adrenal congênita, forma tardia. MÉTODOS: foram incluídas no estudo e avaliadas retrospectivamente 122 pacientes com suspeita clínica de hiperplasia adrenal congênita forma tardia. Essa suspeita clínica incluía sinais e/ou sintomas de hiperandrogenismo (hirsutismo, acne, pele oleosa, irregularidade menstrual, etc.). Todas as pacientes foram submetidas ao teste de estímulo da adrenal com ACTH sintético 0,25 mg (Synacthen®). Após repouso de 60 minutos as amostras foram colhidas nos tempos basal e 60 minutos após a administração de 0,25 mg de ACTH sintético para dosagem de 17-hidroxiprogesterona, sendo mantido o acesso venoso com catéter heparinizado. Foi utilizado o método de radioimunoensaio para realizar as dosagens séricas da 17-hidroxiprogesterona. A sensibilidade e a especificidade da 17-hidroxiprogesterona basal como teste de rastreamento para hiperplasia adrenal congênita foram medidas, avaliando vários pontos de corte. Curvas ROC foram feitas para analisar a performance do teste, utilizando o software Medcalc®. RESULTADOS: a análise por curva ROC mostrou um ponto de corte de 181 ng/dl acima do qual dever-se-ia realizar o teste de estímulo, bem próximo a 200 ng/dl, mais comumente aceito pela literatura. Níveis séricos da 17-hidroxiprogesterona mais altos que 200 ng/dl têm valores preditivo positivo e negativo de 75% e 100% e acurácia de 98,4% como diagnóstico de hiperplasia adrenal não-clássica. CONCLUSÕES: considerando os dados, sugerimos que pacientes com hiperandrogenismo clínico devam iniciar a investigação com 17-hidroxiprogesterona basal e, caso esta se mostre acima de 181 ng/dl, sigam a investigação com o teste de estímulo com ACTH sintético.

Translated abstract

INTRODUCTION: adrenal hyperplasia is a common genetic disorder and 95% of the cases are due to a 21-hydroxylase deficiency. Clinical presentation varies from life-threatening salt-losing adrenal hyperplasia to simple androgenic states, which can be of late-onset and very similar to polycystic ovary syndrome. Diagnosis is usually made by synthetic ACTH provocative tests but efforts are being made to simplify this investigation. OBJECTIVE: to evaluate basal 17-hydroxyprogesterone as a predictor of the provocative test for the diagnosis of late-onset congenial adrenal hyperplasia. METHODS: A total of 122 patients under clinical suspicion of diagnosis of late-onset congenial adrenal hyperplasia were included and retrospectively evaluated in the study. Such suspicion included signs and/or symptoms of hyperandrogenism (hirsutism, acne, oily skin, menstrual irregularity etc.). All the patients were submitted to the 0.25mg synthetic ACTH provocative test (Synacthen®). After resting for 60 minutes, the samples were taken in the basal time and 60 minutes after the administration of 0.25mg synthetic ACTH, in order to assay 17-hydroxiprogesteron, the venous access being kept through a heparinized catheter. Radioimmuoessay was the method used to accomplish the assay of seric 17-hydroxiprogesteron. The sensitivity and specificity of the basal 17-hydroxiprogesteron were measured, assessing several cutoff points. ROC curves were made to analyze the test performance, using the software Medcalc®. RESULTS: ROC curve analysis showed that the best cutoff point was 181 ng/dl, which was very similar to the most common recommendation of 200 ng/dl of the literature. The cutoff point of 200 ng/dl shows positive and negative predictive values of 75 and 100%, and accuracy of 98,4% as a diagnostic test for late-onset adrenal hyperplasia. CONCLUSIONS: considering our data, we suggest that all hyperandrogenic patients should start the investigation with basal 17-hydroxyprogesteron and in case it is above 181 ng/dl, then they should do the synthetic 17-hydroxyprogesteron provocative test.