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Altered Fractional Tetrahydroaldosterone Excretion during Pharmacological Blockade and Activation of the Renin-Aldosterone System^*

Section of Endocrinology and Metabolism, Evans Memorial Department of Clinical Research, The Department of Medicine, University Hospital, Boston University School of Medicine Boston, Massachusetts 02118

Address requests for reprints to: James C. Melby, M.D., University Hospital, 75 East Newton Street, Boston, Massachusetts, 02118.

Tetrahydroaldosterone (THA) is the principal metabolite and generally a good index of aldosterone secretion. This study undertakes the evaluation of the aldosterone secretion rate (ASR) and excretion of THA during pharmacological blockade and activation of the renin-aldosterone system. THA was measured by a simplified RIA and compared to ASR over a period of 28 days in 18 normotensive volunteers receiving either 1) a diuretic [hydrochlorthiazide (HCTZ), 50 mg/day], 2) an angiotensin-converting enzyme inhibitor (MK-421, 10 mg/ day), or 3) combined therapy [HCTZ (50 mg/day) plus MK-421 (10 mg/day)] in a metabolic unit on a controlled diet. Results of this study at 28 days indicate that 1) HCTZ, while producing secondary hyperaldosteronism, lowered the fractional THA ex- cretion (defined as THA/ASR) (from 0.51 to 0.33; P < 0.05); 2) MK-421 produced hypoaldosteronism and a slight increase in the THA/ASR (from 0.43 to 0.53; 0.05 < P < 0.01); 3) combined HCTZ and MK-421 resulted in a normalization of both aldoste-rone secretion and THA/ASR (from 0.51 to 0.50). In conclusion, HCTZ decreases the THA/ASR whereas MK-421 tends to increase it. Combined administration of HCTZ and MK-421 restores the THA/ASR to normal. Therefore, the determination of THA excretion can be an inaccurate index of aldosterone secretion when measured during either pharmacological blockade or activation of the renin-aldosterone system. (J Clin En-docrinol Metab 55: 1217, 1982)

^* This work was supported in part by USPHS Grants 1-T30-AM-21683, 5-T32-AM-07201, 5-PO-HL-18318, and 5-R01-HL-18318 from the NIH.

Received May 20, 1982.