The Unique Patterns of Plasma Aldosterone and 18-Hydroxycorticosterone Concentrations in the 17α-Hydroxylase Deficiency Syndrome*

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Abstract
Deficient 17α-hydroxylation precludes formation of cortisol in the adrenal glands and of sex steroids in the gonads in man, which results in elevated plasma concentrations of deoxycorticosterone (DOC) and corticosterone (B), hypertension, hypokalemia, and suppression of renin and aldosterone production. Subnormal aldosterone levels before and after treatment have suggested an additional enzymatic defect in its formation. To examine this possibility, we studied six patients untreated, on glucocorticoid treatment, and off treatment for short periods of time. To determine the zonal origins of the mineralocorticoid hormones, we measured plasma aldosterone, DOC, B, 18-hydroxycorticosterone (18-OHB), 18-hydroxydeoxycorticosterone, and cortisol along with renin and potassium concentrations at 0800 h and during posture, angiotensin III, and cosyntropin stimulation; after overnight dexamethasone suppressions; and every 4 h during a 24-h period. Elevated DOC (mean ± SEM, 266.7 ± 63.4 ng/dl), B (12,640 ± 3,610 ng/dl), 18-OHB (227.8 ± 76.5 ng/dl), and 18-hydroxydeoxycorticosterone (198.5 ± 41.1 ng/dl) and subnormal aldosterone (4.2 ± 0.7 ng/dl), renin (0.72 ± 0.29 ng/ml·h) and potassium (3.3 ± 0.1 meq/liter) normalized during glucocorticoid treatment. Aldosterone and 18-OHB (46.6 ± 12.6 and 823.2 ± 469 ng/dl, respectively) increased substantially early after treatment ended. Upright posture resulted in a decrease in 18-OHB (n = 2) similar to that in other ACTH-dependent zona fasciculata steroids. Angiotensin III failed to stimulate any steroid. Dexamethasone suppressed and cosyntropin further increased all zona fasciculata steroids, including 18-OHB, without changing aldosterone or renin levels. During the circadian study, 18-OHB correlated significantly with all zona fasciculata steroids, but not with renin. We conclude that 1) discontinuation of treatment permits a prompt surge in ACTH that, in the presence of still normal renin and potassium, substantially stimulates aldosterone and 18-OHB, indicating no additional biosynthetic defects in the zona glomerulosa; 2) the initially excessive ACTH-mediated production of aldosterone and DOC and then only DOC cause renin and aldosterone suppression; and 3) elevated ACTH in the presence of impaired cortisol synthesis contributes to the exaggerated production of the zona fasciculata mineralocorticoids, including 18-OHB.