HORMONAL PHENOTYPE AND HLA-GENOTYPE IN FAMILIES OF PATIENTS WITH CONGENITAL ADRENAL-HYPERPLASIA (21-HYDROXYLASE DEFICIENCY)

The response of 17-hydroxyprogesterone (17-OHP) and cortisol (F) to a 6-hr ACTH stimulation in families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency was studied. These studies demonstrated that siblings who should be heterozygous carriers of the 21-hydroxylase deficiency gene based on HLA genotyping are hormonally different from the general population. In pre- and early pubertal children predicted to be heterozygous carriers of the gene based on HLA genotyping, the 17-OHP level (13.1 ± 4.5 ng/ml), the rate of increase of 17-OHP (0.03 ± 0.01), and the ratio of 17-OHP/F at 6 hr (0.27 ± 0.07) were significantly higher (P < 0.001) than in the control population, (3.9 ± 1.9, 0.009 ± 0.005, and 0.08 ± 0.04 ng/ml, respectively). In late and postpu- bertal males, these hormonal parameters in the heterozygotes (17 ± 9.7, 0.04 ± 0.026, 0.42 ± 0.33 ng/ml, respectively) were significantly higher (P < 0.001) than in the general population (5.3 ± 1.6, 0.009 ± 0.004, and 0.1 ± 0.03 ng/ml, respectively). In postmenarchal females, the mean hormone responses in the heterozygotes (12.1 ± 9.7, 0.03 ± 0.02, and 0.27 ± 0.24 ng/ml, respectively) were significantly higher (P< 0.005, < 0.01, < 0.005, respectively) than in the general population (5.2 ± 2.5, 0.01 ± 0.007, and 0.1 ± 0.04 ng/ml, respectively). However, the overlapping values did not permit a clear differentiation of the hormonal responses in these two groups. Another (ACTH) stimulation in one family demonstrated that a father of a patient probably is a previously unrecognized homozygous affected patient and, thus, revision of the congenital adrenal hyperplasia (CAH) genotype for this family was required. Speculation: In families of patients with CAH due to 21-hydroxylase deficiency, siblings predicted to be heterozygous carriers of the gene for 21 hydroxylase deficiency based on HLA genotyping, will express a mild enzyme deficiency by hormonal testing. © 1979 International Pediatric Research Foundation, Inc.