Zona glomerulosa function after life-long suppression in two siblings with the hypertensive virilizing form of congenital adrenal hyperplasia.

The function of the adrenal zona glomerulosa was studied in two pubertal siblings with the hypertensive virilizing form of congenital adrenal hyperplasia who had never been treated. Initially, their plasma 11-deoxycortisol and 11-deoxycorticosterone (DOC) levels were very high, PRA was suppressed, and plasma aldosterone and 18-hydroxycorticosterone (18-OHB) were undetectable. To selectively study zona glomerulosa function, the patients and five normal subjects were given dexamethasone (2 mg/day; thus suppressing zona fasciculata function), and their sodium intake was restricted to 10 mmol/day. After 3-5 days, the zona glomerulosa was stimulated with either angiotensin II or potassium chloride. The same protocol was repeated in the patients at various intervals up to 39 months after beginning maintenance therapy with dexamethasone (0.25 mg twice daily). PRA, plasma aldosterone, and 18-OHB remained low during the first 6 months of treatment. After the first year, PRA recovered, and the zona glomerulosa began to respond. Plasma aldosterone and 18-OHB levels reached normal basal and stimulated values in one of the patients after 2 yr of treatment, but remained subnormal after 39 months of treatment in the other patient. Both patients, however, had persistently elevated plasma DOC concentrations, suggesting slight but definite impairment of 11 beta-hydroxylation in the zona glomerulosa. We conclude that in spite of a severe and persistent 11 beta-/18-hydroxylation deficiency in the zona fasciculata, the zona glomerulosa can recover almost completely after prolonged treatment. Appropriate stimulation, however, discloses a minor 11 beta-hydroxylation impairment also in the zona glomerulosa. In addition, the lack of parallelism in zona glomerulosa 11 beta- and 18-hydroxylation of DOC provides evidence for the concept of different 18-hydroxylating systems in the adrenal cortex.