Adrenal response to adrenocorticotropin hormone and HLA typing of subjects with different degrees of 21-hydroxylase deficiency

RESUMO

1. To evaluate different degrees of 21-hydroxylase (21-OH) deficiency we studied the 17-hydroxyprogesterone (17-OHP) and cortisol response to the adrenocorticotropin hormone (ACTH) stimulation test. In a study of 13 families we characterized the relatives of patients with classical 21-OH deficiency using HLA antigen typing and the ACTH test. The subjects were divided into five groups 12 patients with the classical form, 11 patients with the nonclassical form, 38 heterozygotes, 6 normal homozygotes and 33 controls. 2. The 17-hydroxyprogesterone response to ACTH (mean +/- SD) varied as follows according to the degree of 21-OH deficiency 25442 +/- 15718 ng/dl for the classical group, 4198 +/- 1637 ng/dl for the nonclassical group, 348 +/- 267 ng/dl for the heterozygotes, 127 +/- 81 ng/dl for normal homozygotes, and 164 +/- 120 ng/dl for the controls. Basal plasma cortisol did not differ among the five groups. The cortisol response to ACTH was not different among controls (30 +/- 8 micrograms/dl), normal homozygotes (28 +/- 7 micrograms/dl) and heterozygotes (26.5 +/- 7 micrograms/dl). The cortisol response was decreased in the patient groups and was lower in the classical (14 +/- 10 micrograms/dl) than in the nonclassical group (20 +/- 4 micrograms/dl). 3. In most families (11/13), HLA typing was informative in identifying the 21-OH deficiency containing haplotype, which correlated with the hormonal profile. In two families there was no correlation between the HLA genotype and the clinical expression of 21-OH activity for two HLA identical pairs of siblings