Adrenarche does not occur in treated patients with congenital adrenal hyperplasia resulting from 21-hydroxylase deficiency

There have been few studies of adrenarche in patients with congenital adrenal hyperplasia (CAH). We have therefore sought to detect the onset of adrenarche in CAH patients and to investigate whether its evolution was influenced by the severity of the disease, the age at the onset of substitution therapy, or both.

Sixteen female CAH patients were studied longitudinally for 4-11 years. They were all given substitution therapy and treatments were well controlled as judged by repeated hormonal evaluations. The patients were divided into two groups: group A consisted of 10 girls with a severe classic (congenital) form, while group B included 6 girls presenting with a non-classic form.

Circulating levels of dehydroepiandrosterone sulphate (DHEAS), were determined as an indicator of adrenarche. Hormonal assessments included measurements of 17-hydroxyprogesterone (17-OHP), testosterone, ACTH and plasma renin activity. All were estimated by conventional specific assays.

Mean levels were analysed in consecutive two-year age periods. In group A, DHEAS levels were significantly lower at any age than in control subjects, and lower than in patients with non-classic CAH. DHEAS levels showed no increment with age. In group B, plasma DHEAS levels were surprisingly high for the age at the time of diagnosis, declining gradually on substitution therapy, although they remained somewhat higher than in group A.

The high DHEAS levels observed in untreated girls of group B are probably the result of chronic hypersecretion of ACTH. Under well controlled, non-suppressive substitution therapy, patients with congenital adrenal hyperplasia showed no rise in DHEAS levels at the physiological age of adrenarche whatever the degree of the enzyme defect and whatever the age at onset of therapy.