Studies of the c-21 and c-19 steroids and hla genotyping in siblings and parents of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

In 24 families of patients with congenital adrenal hyperplasia (21-hydroxylase deficiency), HLA genotyping and a 360-min ACTH stimulation test were performed in 34 siblings, 37 parents, and 11 other family members. 17-desoxy-, 17-hydroxy-, and C-19 steroids were determined before and after stimulation with ACTH in order to test the adrenocortical function in family members with 21-hydroxylase deficiency. The response of the family members predicted to be heterozygous and those predicted to be genetically unaffected by HLA genotyping were compared to the general population. The study demonstrates that only the ACTH-stimulated 17- hydroxyprogesterone level may be useful in detecting heterozygosity. All other stimulated hormones (A5-17-hydroxypregnenolone, 11-desoxycortisol and cortisol in the glucocorticoid pathway and progesterone, desoxycorticosterone, corticosteront, and aldosterone in the mineralocorticoid pathway, and A4-androstenedione, dehydroepiandrosterone, and testosterone in the androgen pathway), whether analyzed alone or in combination, did not discriminate between the general and the heterozygous populations. In summary, in siblings predicted to be heterozygous, by HLA genotyping and obligate heterozygous parents, a mild 2].-hydroxylase deficiency was expressed in the 17-hydroxy pathway but was not evident in the 17-desoxy pathway or C-19 androgens after ACTH stimulation.