Effects of continued adrenocorticotropin stimulation on the mineralocorticoid hormones in classical and nonclassical simple virilizing types of 21-hydroxylase deficiency

• Published in: The journal of clinical endocrinology and metabolism Vol. 60; no. 6; p. 1057
• Main Authors: Kater, C E, Biglieri, E G, Wajchenberg, B
• Format: Journal Article
• Language: English
• Published: United States 01.06.1985
• Subjects: 18-Hydroxycorticosterone - blood; Adrenal Hyperplasia, Congenital - blood; Adrenal Hyperplasia, Congenital - drug therapy; Adrenal Hyperplasia, Congenital - enzymology; Adrenocorticotropic Hormone - pharmacology; Adult; Aldosterone - blood; Child, Preschool; Desoxycorticosterone - blood; Female; Glucocorticoids - blood; Humans; Hydrocortisone - blood; Male; Mineralocorticoids - blood; Steroid Hydroxylases - deficiency
• ISSN: 0021-972X
• DOI: 10.1210/jcem-60-6-1057

Superphysiological doses of ACTH were administered for 3 consecutive days to nine patients with CAH, five with the classical simple virilizing (CSV) type and four with nonclassical simple virilizing type (NCSV; late onset), receiving a sodium-restricted diet. In the CSV patients, cortisol levels were lower [4.9 +/- 2.2 (+/- SEM) micrograms/dl] than in the NCSV patients (10.9 +/- 3.8; P less than 0.005) and normal subjects (10.7 +/- 4.0; P less than 0.05). ACTH produced a subnormal increase to only 14.5 micrograms/dl by day 3. In the NCSV patients, cortisol rose slowly during the first 24 h, but reached normal response levels by 48 h (42.5 +/- 11.5 micrograms/dl). In all patients, basal plasma corticosterone and 18-hydroxydeoxycorticosterone (18-OHDOC) levels were normal, but deoxycorticosterone (DOC) was elevated at 25.3 +/- 5.0 ng/dl (P less than 0.05). ACTH failed to increase plasma levels of DOC, corticosterone, and 18-OHDOC. Aldosterone and 18-hydroxycortisol were elevated in both groups [29.1 +/- 5.8 (P less than 0.02) and 83.8 +/- 15.3 (P less than 0.01) ng/dl, respectively] and increased briskly after the first 24 h of ACTH. However, neither steroid returned to normal levels in the CSV group, but both did in the NCSV group. Paired values of stimulated cortisol and aldosterone in normal subjects and CSV and NCSV patients (n = 76) were significantly negatively correlated (r = -0.63; P less than 0.001), suggesting that cortisol inhibits aldosterone biosynthesis. Prolonged ACTH administration after initial increases returned aldosterone and 18-hydroxycortisol levels from the zona glomerulosa to baseline values in the NCSV type, but not in the CSV type. The capacity to increase cortisol levels, which occurred only in NCSV patients, is linked to the reduction of aldosterone in the zona glomerulosa. In contrast, in both types of 21-hydroxylase deficiency, sustained impairment of both the 17-hydroxy pathway (cortisol) and the 17-deoxy pathway of the zona fasciculata (DOC, corticosterone, and 18-OHDOC) was demonstrated.