Adult manifestation of congenital adrenal hyperplasia due to incomplete 21-hydroxylase deficiency mimicking polycystic ovarian disease

Abstract

This study was carried out to document the postpubertal presentation of congenital adrenal hyperplasia (CAH), to elaborate the diagnostic criteria for it, and to investigate family members of CAH patients. Serum 17-hydroxyprogesterone (17OHP) was measured in normal women and 25 hirsute oligomenorrheic patients, five of whom were shown to have CAH. These five CAH patients, as a group, had significantly elevated levels of 17OHP when compared to normal and hirsute women, although the other 20 hirsute oligomenorrheic women also had higher levels of 17OHP than the follicular phase control subjects. A single intravenous bolus of 0.25 mg of adrenocorticotropic homone (ACTH) caused much larger increases in 17OHP in all five CAH patients than in the control and hirsute women. The five CAH patients had decreased cortisol but normal 11-deoxycortisol responses to ACTH, thus indicating 21-hydroxylase deficiency (21HD). Clinically, they were indistinguishable from women with polycystic ovarian disease (PCO) and had basal serum levels of androgens and urinary 17-ketosteroids which were similar to those found in 47 other women presenting with the complaint of hirsutism. However, the androstenedione levels and androstenedione/cortisol ratios in response to ACTH were significantly higher in the five CAH patients than in both the normal and hirsute women. Of seven family members tested, two fathers and one mother had an intermediate 17OHP response to ACTH, thus suggesting heterozygosity. Human lymphocyte antigen (HLA) typing on family members indicated that the inheritance of the disorder may be linked to B antigens. Two siblings of one of the CAH patients had normal 17OHP responses to ACTH and also had a different HLA-B complement. These data document the existence of adult manifestation of CAH, due to 21 HD. This disorder presents with androgen excess and oligomenorrhea or amenorrhea and mimicks PCO. The diagnosis of it highes upon the post-ACTH rise in 17OHP, whereas the levels of serum androgens and urinary 17-ketosteroids may be inconclusive.