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. 1978 Jul;62(1):162–168. doi: 10.1172/JCI109101

Effect of Aminoglutethimide on Blood Pressure and Steroid Secretion in Patients with Low Renin Essential Hypertension

Addison A Taylor 1,2, Jerry R Mitchell 1,2, Frederic C Bartter 1,2, Wayne R Snodgrass 1,2, Randolph J McMurtry 1,2, John R Gill Jr 1,2, Ronald B Franklin 1,2
PMCID: PMC371749  PMID: 149141

Abstract

An inhibitor of adrenal steroid biosynthesis, aminoglutethimide, was administered to seven patients with low renin essential hypertension, and the antihypertensive action of the drug was compared with its effects on adrenal steroid production. In all patients aldosterone concentrations in plasma and urine were within normal limits before the study. Mean arterial pressure was reduced from a pretreatment value of 117±2 (mean±SE) mm Hg to 108±3 mm Hg after 4 days of aminoglutethimide therapy and further to 99±3 mm Hg when drug administration was stopped (usually 21 days). Body weight was also reduced from 81.6±7.2 kg in the control period to 80.6±7.0 kg after 4 days of drug treatment and to 80.1±6.7 kg at the termination of therapy. Plasma renin activity was not significantly increased after 4 days of treatment but had risen to the normal range by the termination of aminoglutethimide therapy. Mean plasma concentrations of deoxycorticosterone and cortisol were unchanged during aminoglutethimide treatment whereas those of 18-hydroxydeoxycorticosterone, progesterone, 17α-hydroxyprogesterone, and 11-deoxycortisol were increased as compared to pretreatment values. In contrast, aminoglutethimide treatment reduced mean plasma aldosterone concentrations to about 30% of control values. Excretion rates of 16β-hydroxydehydroepiandrosterone, 16-oxo-androstenediol, 17-hydroxycorticosteroids and 17-ketosteroids, and the secretion rate of 16β-hydroxydehydroepiandrosterone were not significantly altered by aminoglutethimide treatment whereas the excretion rate of aldosterone was reduced from 3.62±0.5 (mean±SE) in the control period to 0.9±0.2 μg/24 h after 4 days and to 1.1±0.3 μg/24 h at the termination of aminoglutethimide treatment.

The gradual lowering of blood pressure and body weight during aminoglutethimide therapy is consistent with the view that the antihypertensive effect of the drug is mediated through a reduction in the patients' extracellular fluid volume, probably secondary to the persistent decrease in aldosterone production. The observation that chronic administration of aminoglutethimide lowered blood pressure in these patients and elevated their plasma renin activity to the normal range without decreasing production of the adrenal steroids, deoxycorticosterone, 18-hydroxydeoxycorticosterone, and 16β-hydroxydehydroepiandrosterone, makes it unlikely that these steroids are responsible either for the decreased renin or the elevated blood pressure in patients with low renin essential hypertension.

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Selected References

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  1. Abraham G. E., Swerdloff R., Tulchinsky D., Odell W. D. Radioimmunoassay of plasma progesterone. J Clin Endocrinol Metab. 1971 May;32(5):619–624. doi: 10.1210/jcem-32-5-619. [DOI] [PubMed] [Google Scholar]
  2. Beevers D. G., Morton J. J., Nelson C. S., Padfield P. L., Titterington M., Tree M. Angiotensin II in essential hypertension. Br Med J. 1977 Feb 12;1(6058):415–415. doi: 10.1136/bmj.1.6058.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown J. J., Fraser R., Love D. R., Ferriss J. B., Lever A. F., Robertson J. I., Wilson A. Apparently isolated excess deoxycorticosterone in hypertension. A variant of the mineralocorticoid-excess syndrome. Lancet. 1972 Aug 5;2(7771):243–247. doi: 10.1016/s0140-6736(72)91685-6. [DOI] [PubMed] [Google Scholar]
  4. Bühler F. R., Burkart F., Lütold B. E., Küng M., Marbet G., Pfisterer M. Antihypertensive beta blocking action as related to renin and age: a pharmacologic tool to identify pathogenetic mechanisms in essential hypertension. Am J Cardiol. 1975 Oct 31;36(5):653–669. doi: 10.1016/0002-9149(75)90168-x. [DOI] [PubMed] [Google Scholar]
  5. CONN J. W., COHEN E. L., ROVNER D. R. SUPPRESSION OF PLASMA RENIN ACTIVITY IN PRIMARY ALDOSTERONISM. JAMA. 1964 Oct 19;190:213–221. doi: 10.1001/jama.1964.03070160037008. [DOI] [PubMed] [Google Scholar]
  6. Carey R. M., Douglas J. G., Schweikert J. R., Liddle G. W. The syndrome of essential hypertension and suppressed plasma renin activity. Normalization of blood pressure with spironolactone. Arch Intern Med. 1972 Dec;130(6):849–854. [PubMed] [Google Scholar]
  7. Catt K. J., Cran E., Zimmet P. Z., Best J. B., Cain M. D., Coghlan J. P. Angiotensin II blood-levels in human hypertension. Lancet. 1971 Mar 6;1(7697):459–464. doi: 10.1016/s0140-6736(71)91085-3. [DOI] [PubMed] [Google Scholar]
  8. Dunn M. J., Tannen R. L. Low-renin hypertension. Kidney Int. 1974 May;5(5):317–325. doi: 10.1038/ki.1974.47. [DOI] [PubMed] [Google Scholar]
  9. Farmer R. W., Roup W. G., Jr, Pellizzari E. D., Fabre L. F., Jr A rapid aldosterone radioimmunoassay. J Clin Endocrinol Metab. 1972 Jan;34(1):18–22. doi: 10.1210/jcem-34-1-18. [DOI] [PubMed] [Google Scholar]
  10. Fishman L. M., Küchel O., Liddle G. W., Michelakis A. M., Gordon R. D., Chick W. T. Incidence of primary aldosteronism uncomplicated "essential" hypertension. A prospective study with elevated aldosterone secretion and suppressed plasma renin activity used as diagnostic criteria. JAMA. 1968 Aug 12;205(7):497–502. doi: 10.1001/jama.205.7.497. [DOI] [PubMed] [Google Scholar]
  11. Fishman L. M., Liddle G. W., Island D. P., Fleischer N., Küchel O. Effects of amino-glutethimide on adrenal function in man. J Clin Endocrinol Metab. 1967 Apr;27(4):481–490. doi: 10.1210/jcem-27-4-481. [DOI] [PubMed] [Google Scholar]
  12. Gower D. B. Modifiers of steroid-hormone metabolism: a review of their chemistry, biochemistry and clinical applications. J Steroid Biochem. 1974 Aug;5(5):501–523. doi: 10.1016/0022-4731(74)90051-x. [DOI] [PubMed] [Google Scholar]
  13. HELMER O. M. RENIN ACTIVITY IN BLOOD FROM PATIENTS WITH HYPERTENSION. Can Med Assoc J. 1964 Jan 25;90:221–225. [PMC free article] [PubMed] [Google Scholar]
  14. Ito T., Woo J., Haning R., Horton R. A radioimmunoassay for aldosterone in human peripheral plasma including a comparison of alternate techniques. J Clin Endocrinol Metab. 1972 Jan;34(1):106–112. doi: 10.1210/jcem-34-1-106. [DOI] [PubMed] [Google Scholar]
  15. Kurtz A. B., Bartter F. C. Radioimmunoassays for aldosterone and deoxycorticosterone in plasma and urine. Steroids. 1976 Jul;28(1):133–142. doi: 10.1016/0039-128x(76)90132-x. [DOI] [PubMed] [Google Scholar]
  16. Laragh J. H., Sealey J., Brunner H. R. The control of aldosterone secretion in normal and hypertensive man: abnormal renin-aldosterone patterns in low renin hypertension. Am J Med. 1972 Nov;53(5):649–663. doi: 10.1016/0002-9343(72)90160-x. [DOI] [PubMed] [Google Scholar]
  17. Mancheno-Rico E., Kuchel O., Nowaczynski W., Seth K. K., Sasaki C., Dawson K., Genest J. A dissociated effect of amino-glutethimide on the mineralocorticoid secretion in man. Metabolism. 1973 Feb;22(2):123–132. doi: 10.1016/0026-0495(73)90262-x. [DOI] [PubMed] [Google Scholar]
  18. Melby J. C., Dale S. L., Grekin R. J., Gaunt R., Wilson T. E. 18-Hydroxy-11-deoxycorticosterone (18-OH-DOC) secretion in experimental and human hypertension. Recent Prog Horm Res. 1972;28:287–351. [PubMed] [Google Scholar]
  19. Menard J., Catt K. J. Measurement of renin activity, concentration and substrate in rat plasma by radioimmunoassay of angiotensin I. Endocrinology. 1972 Feb;90(2):422–430. doi: 10.1210/endo-90-2-422. [DOI] [PubMed] [Google Scholar]
  20. Messerli F. H., Kuchel O., Nowaczynski W., Seth K., Honda M., Kubo S., Boucher R., Tolis G., Genest J. Mineralocorticoid secretion in essential hypertension with normal and low plasma renin activity. Circulation. 1976 Mar;53(3):406–410. doi: 10.1161/01.cir.53.3.406. [DOI] [PubMed] [Google Scholar]
  21. Mitchell J. R., Taylor A. A., Pool J. L., Lake C. R., Rollins D. E., Bartter F. C. Renin-aldosterone profiling in hypertension. Ann Intern Med. 1977 Nov;87(5):596–312. doi: 10.7326/0003-4819-87-5-596. [DOI] [PubMed] [Google Scholar]
  22. New M. I., Seaman M. P. Secretion rates of cortisol and aldosterone precursors in various forms of congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1970 Mar;30(3):361–371. doi: 10.1210/jcem-30-3-361. [DOI] [PubMed] [Google Scholar]
  23. SOBEL C., GOLUB O. J., HENRY R. J., JACOBS S. L., BASU G. K. Study of the Norymberski methods for determination of 17-ketogenic steroids (17-hydroxycorticosteroids) in urine. J Clin Endocrinol Metab. 1958 Feb;18(2):208–221. doi: 10.1210/jcem-18-2-208. [DOI] [PubMed] [Google Scholar]
  24. Shade R. E., Grim C. E. Suppression of renin and aldosterone by small amounts of DOCA in normal man. J Clin Endocrinol Metab. 1975 Apr;40(4):652–658. doi: 10.1210/jcem-40-4-652. [DOI] [PubMed] [Google Scholar]
  25. Trendelenburg U. Mechanisms of supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol Rev. 1966 Mar;18(1):629–640. [PubMed] [Google Scholar]
  26. Vaughan E. D., Jr, Laragh J. H., Gavras I., Bühler F. R., Gavras H., Brunner H. R., Baer L. Volume factor in low and normal renin essential hypertension. Treatment with either spironolactone or chlorthalidone. Am J Cardiol. 1973 Sep 20;32(4):523–532. doi: 10.1016/s0002-9149(73)80044-x. [DOI] [PubMed] [Google Scholar]
  27. Vigersky R. A., Easley R. B., Loriaux D. L. Effect of fluoxymesterone on the pituitary-gonadal axis: the role of testosterone-estradiol-binding globulin. J Clin Endocrinol Metab. 1976 Jul;43(1):1–9. doi: 10.1210/jcem-43-1-1. [DOI] [PubMed] [Google Scholar]
  28. Williams G. H., Braley L. M., Underwood R. H. The regulation of plasma 18-hydroxy 11-deoxycorticosterone in man. J Clin Invest. 1976 Jul;58(1):221–229. doi: 10.1172/JCI108453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Woods J. W., Liddle G. W., Michelakis A. M., Brill A. B. Effect of an adrenal inhibitor in hypertensive patients with suppressed renin. Arch Intern Med. 1969 Apr;123(4):366–370. [PubMed] [Google Scholar]

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