The Hypothalamic-Pituitary-Adrenal Axis in Partial (Late-Onset) 21-Hydroxylase Deficiency*

Patients with late-onset congenital adrenal hyperplasia (LOCAH) due to partial 21-hydroxylase deficiency have no clinical or biochemical evidence of hypocortisolism. In contrast, patients with the classical forms of CAH frequently develop adrenal insufficiency, characterized by elevated plasma ACTH and low serum cortisol levels. To examine the various components of the hypothalamic-pituitary-adrenal axis in patients with LOCAH, we studied 12 patients with this disorder (10 females and 2 males; age range, 51/2–36 yr). Plasma ACTH and serum cortisol, 17-hydroxyprogesterone (17-OHP), and androstenedione (Adione) concentrations were measured after administration of ovine CRH (oCRH); 1 μg/kg at 2000 h) and in the unstimulated state (every 30–60 min for 24 h). The patients’ oCRH-stimulated ACTH, cortisol, and Adione responses did not differ from those of normal subjects, whereas their serum 17-OHP concentrations were elevated both basally and after oCRH (P < 0.05). The patients’ unstimulated 24-h ACTH and cortisol levels were normal and exhibited normal diurnal variability. Cortisol pulse frequency was normal. The patients’ unstimulated serum 17-OHP levels exceeded those in the normal subjects at all times (P < 0.01) and exhibited diurnal variability paralleling that of ACTH and cortisol. Unstimulated serum Adione levels in 4 adult women were in the normal or low normal range, except between 0200-0730 h when they were moderately elevated (P < 0.05). We conclude that the ACTH-cortisol component of the hypothalamic-pituitary-adrenal axis is in normal equilibrium in this group of patients with LOCAH. Because serum Adione levels were elevated only briefly, we suggest that peripheral tissue conversion of 17-OHP to androgens may be the primary cause of the hirsutism and acne in these patients.