Long-term treatment of mineralocorticoid excess syndromes

Abstract

Recognition of the pathogenesis of secondary forms of hypertension is often considered the key to appropriate choice of treatment. We here present the results of a prolonged clinical follow-up (from 1 to 20 years) of a large number of patients with mineralocorticoid excess syndromes (MES), including over 100 patients with primary aldosteronism (PA), 3 cases with dexamethasone-suppressible aldosteronism (DSA), 3 cases of apparent mineralocorticoid excess (AME) Type II, and 4 patients with 17-hydroxylase deficiency (17OHDS). The patients with PA have been divided in two subgroups, one of 69 cases followed between 1973 and 1982, and the second of 37 patients studied between 1983 and 1992; 33 further cases were not evaluated due to poor compliance. In group I, 26 patients underwent surgery (23 unilateral adenoma, 1 primary hyperplasia, 2 bilateral nodular hyperplasia); at 5 years 50% had normal blood pressure, 25% had mild hypertension and 25% had moderate to severe hypertension. Forty-three patients with either adenoma (APA) or idiopathic aldosteronism (IHA) received long-term spironolactone treatment. Among them, 13 required the addition of thiazide and/or β-blockers, while 13 were switched to an amiloride/thiazide combination (± beta blockers) due to side-effects to spironolactone (gynecomastia 6/20 males, menstrual upser or breast pain in 7/23 females). In group II, 12 patients underwent surgery (11 adenoma, 1 primary hyperplasia) with a similar outcome at 3 years as in group I; 25 patients were put on either K canrenoate (11) or Ca + + channel blockers (14) with or without KCl supplementation; in 8 cases these two drugs were combined according to blood pressure levels achieved during the follow-up. ACE inhibitors, thiazide, ketanserin, and ketoconazole were given in selected cases. Gynecomastia occurred only in 2 out of 16 males while on K canrenoate and no side effects were reported in females on the same regimen. The other patients with ACTH-dependent MES were all treated initially with dexamethasone (DEX) at low doses (0.25–1 mg q.d). In all cases potassium remained within the normal limits; blood pressure was not adequately controlled in all 3 cases of DSH and in the oldest patient with 17OHDS and AME Type II, respectively, in spite of the normalization of the hormonal patterns. Ca + + antagonists have been added in these cases, and K canrenoate substituted for DEX in the AME Type II patient. In conclusion, surgical removal or long term treatment of ME with specific antagonists or inhibitors may be inadequate to normalize high blood pressure in almost a half of the patients with MES. This could be due, inter alia, to the persistence of vascular abnormalities, to the coexistence of essential hypertension, or to our only partial understanding of the pathophysiology of some of these syndromes (e.g., IHA and AME).