Decreased cortisol secretion in nonclassical 21-hydroxylase deficiency before and during glucocorticoid therapy.

Abstract

The cortisol response in patients with nonclassical 21-hydroxylase deficiency (NC21OHD) was assessed before and during hydrocortisone therapy and the findings were related to genotype. Comparative study. The study sample comprised 41 patients (10 males) with NC21OHD, divided into two groups according to the genetic analysis of the CYP21 gene: Group A carried two mild mutations (n = 29), and Group B were compound heterozygotes for one mild and one severe mutation (n = 12). The 250 microg short ACTH test was performed at diagnosis. To evaluate the degree of treatment-induced suppression of adrenal function, 31 patients also underwent the 1 microg/1.73 m2 ACTH test during hydrocortisone therapy. Basal and stimulated cortisol levels and the increment in cortisol response were compared between Groups A and B and between the whole patient sample and healthy controls (32 subjects for the 250 microg test and 29 for the 1 microg/1.73 m2 test). The basal, stimulated, and incremental cortisol levels were similar in Groups A and B; therefore, all the patients were considered together. At diagnosis, the basal cortisol levels were similar in the patients and controls, but the stimulated and incremental cortisol levels were significantly lower in the patients (p <0.001 for both). During hydrocortisone therapy, the patients had slightly higher basal cortisol levels than the controls (p = 0.04), but significantly lower stimulated and incremental cortisol levels (p <0.001 for both). Cortisol levels in NC21OHD are similar in patients carrying two mild mutations and in compound heterozygotes for one mild and one severe mutation. Stimulated and incremental cortisol levels in response to the short ACTH test might be decreased not only during but also before hydrocortisone therapy. Therefore, coverage with a stress dose of hydrocortisone during serious intercurrent illness or surgery is recommended in patients with NC21OHD, especially those previously treated with corticosteroids.