Zona Fasciculata Origin of 18-Hydroxycorticosterone in the Chronically Suppressed Zona Glomerulosa*

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Abstract
18-Hydroxycorticosterone (18-OHB) is produced n i the zona glomerulosa (ZG). Its secretory patterns are closely related to those of aldosterone and usually unrelated to those of cortisol or other zona fasciculata (ZF) steroids. Dissociative production of 18-OHB and aldosterone is only found in patients with the corticosterone-methyl-oxidase type II deficiency or the 17α-hydroxylase deficiency form of congenital adrenal hyperpla-sia. In the latter, however, excessive 18-OHB production most likely originates in the ZF. We studied an additional condition in which the ZG is chronically suppressed to determine if the ZF also produces 18-OHB. Eight patients, previously treated with 100–300 mg spironolactone (Aldactone) daily for an average of 86 days, were studied under metabolically balanced conditions 7–14 days after the removal of one adrenal gland containing an aldosterone-producing adenoma. Four of these subjects had no aldosterone or 18-OHB response to angiotensin III (des-Asp1-angiotensin II) infusion [10 ng/kg-min for 20 min; from 3.7 ± 1.3 t o 4.6 ± 1.0 and from 6.2 ± 1.4 to 8.1 ± 1.3 ng/dl, respectively (mean ± SE)], indicating suppression of the ZG. The administration of cosyntropin (Cortrosyn; 250-/μg iv bolus) to these same patients, however, effected a significant increase (P < 0.001) in 18-OHB (from 6.6 ± 1.7 to 26.7 ± 2.5 ng/dl) without changing the aldosterone level (5.4 ± 0.6 to 7.0 ± 1.4 ng/dl). The other four patients had ZG responsive to stimulation with angiotensin III, increasing aldosterone and 18-OHB production significantly (P < 0.025). Renin and potassium levels were normal and comparable in both groups. Other ZF steroids (cortisol, corticoster-one, deoxycorticosterone, and 18-hydroxydeoxycorticosterone) also were within normal limits and responded normally to stimulation with cosyntropin in both groups. We conclude that in the remaining adrenal gland, after the removal of an aldosterone-producing tumor, 18-OHB can be produced in the ZF. The requisite conditions are a chronically suppressed ZG and the added stimulus of ACTH, exogenously administered, to provide enough substrate (corticosterone) for 18-hydroxylation in the ZF. (J Clin Endocrinol Metab55: 628, 1982)