HLA and hormonal studies in 5 patients with late-onset 21-hydroxylase deficiency syndrome (21OHDS).
Late-onset 21-hydroxylase deficiency (21OHD) presents biochemical evidence of 21OHD and virilization in peri-or postpubertal age; it has been demonstrated that late-onset 21OHD is linked to HLA system. We present the HLA typing, the baseline and the ACTH-stimulated hormonal levels in 5 patients with late-onset 21OHD and in their family members. We identified 3 HLA identical male sibs within their respective families, 2 sibs sharing one haplotype with the affected member and 2 homozygous normal sibs. We observed elevated baseline (greater than 4 ng/ml) and ACTH-stimulated 17-hydroxyprogesterone levels, increased baseline Androstenedione levels, slightly elevated or normal DHEA-S and Testosterone values and subnormal response of Cortisol levels to ACTH in patients and in the HLA-identical sibs, reduced SHBG levels in patients but not in their identical sibs. The heterozygous family members presented hyperresponsiveness of 17-hydroxyprogesterone but not of androgens after ACTH. We confirm that late-onset of 21OHD is an autosomal recessive disease linked to HLA-B; there is in fact biochemical evidence of mild 21OHD in patients and in their HLA identical sibs and 17-hydroxyprogesterone levels in the range of heterozygotes for classical 21OHD in parents and sibs predicted by HLA to be carriers. Thus HLA typing and hormonal data, particularly 17-hydroxyprogesterone, are useful, also in this form of congenital hyperplasia, in detecting heterozygotes.
D019326:17-alpha-Hydroxyprogesterone; D000293:Adolescent; D000311:Adrenal Glands / Q000473:pathology*; D000312:Adrenal Hyperplasia, Congenital; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000728:Androgens / Q000097:blood; D005260:Female; D006680:HLA Antigens / Q000032:analysis*; D006579:Heterozygote; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006908:Hydroxyprogesterones / Q000097:blood; D006965:Hyperplasia / Q000097:blood / Q000235:genetics; D008297:Male; D013250:Steroid Hydroxylases / Q000172:deficiency*
D000728:Androgens; D006680:HLA Antigens; D006728:Hormones; D006908:Hydroxyprogesterones; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D006854:Hydrocortisone