Evidence for a New Mineralocorticoid in Patients with Low-Renin Essential Hypertension

Patients with low-renin essential hypertension have certain features consistent with excessive mineralocorticoid activity. Because known mineralocorticoids are normal in the majority of low-renin essential hypertension patients, an unknown mineralocorticoid was sought in the urine of such patients. Urine extracts from patients with low-renin essential hypertension were assayed for mineralocorticoid activity in adrenalectomized rats and found to contain more such activity than could be accounted for by the known mineralocorticoids in the extracts. The factor responsible for the unexplained mineralocorticoid activity was purified and then identified by mass spectral analysis as 16/3-hydroxydehy-droepiandrosterone (16β-OH-DHEA). Synthetic 16β-OH-DHEA was found to have a mineralocorticoid potency one-fortieth that of aldosterone in the rat bioassay. The mineralocorticoid effects of both the urine extracts and the synthetic steroid were blocked in the rat by spironolactone, a mineralocorticoid antagonist. A specific assay for 16β-OH-DHEA was developed, and its level in the urine was found to be elevated in patients with low-renin essential hypertension.