18-Hydrocorticosterone Biosynthesis in an Aldosterone Secreting Tumor and in the Surrounding Nontumorous Adrenal Gland ∗

A greater than normal concentration of aldosterone has been found in adrenal tumors from patients with primary aldosteronism (1). 18-Hydroxycorticosterone is probably an intermediary product in the conversion of corticosterone to aldosterone (2). This conversion takes place in the zona glomerulosa. The parallel changes in secretion rates of aldosterone and 18-hydroxycorticosterone which have been observed in man under a variety of conditions support the intermediary role of 18-hydroxycorticosterone (3). However, 18-hydroxycorticosterone is also synthesized in the fasciculata-reticularis zones of the cow adrenal gland (4), and to a lesser degree, in the inner zones of the rat adrenal gland (5).

The present report describes the conversion of corticosterone-4-¹⁴C to 18-hydroxycorticosterone and aldosterone by an aldosterone producing tumor and the surrounding nontumorous adrenal tissue. Only the mitochondrial fraction of both tissues contained converting activity. The tumor converted 4 times more corticosterone-4-¹⁴C to aldosterone than did the surrounding adrenal tissue but the conversion rate to 18-hydroxycorticosterone was the same for both tissues. Since it is likely that the zona glomerulosa of the nontumorous adrenal tissue of a patient with primary aldosteronism is inactive, these data suggest that the zona fasciculata-reticularis of the human adrenal gland can synthesize 18-hydroxycorticosterone.

Case report. The patient was a 60-year-old white male with a history of benign hypertension and hypokalemia. Aldosterone excretion and secretion rates remained elevated, 27 and 306 μg/24 hr respectively, after the patient was eating a 350 meq sodium diet for 4 days, and the plasma renin concentrations were depressed after 6 days of a 10 meq sodium diet. Plasma cortisol, 17-hydroxycorticoid and 17-ketosteroid excretion were normal. Laboratory tests ruled out the diagnosis of pheochromocytoma and renal artery stenosis.

At surgery, the left adrenal gland appeared grossly normal.