LONG-TERM TREATMENT OF MINERALOCORTICOID EXCESS SYNDROMES

Recognition of the pathogenesis of secondary forms of hypertension is often considered the key to appropriate choice of treatment. We here p resent the results of a prolonged clinical follow-up (from I to 20 yea rs) of a large number of patients with mineralocorticoid excess syndro mes (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 wi th 17-hydroxylase deficiency (17OHDS). The patients with PA have been divided in two subgroups, one of 69 cases followed between 1973 and 19 82, and the second of 37 patients studied between 1983 and 1992; 33 fu rther cases were not evaluated due to poor compliance. In group I, 26 patients underwent surgery (23 unilateral adenoma, I primary hyperplas ia, 2 bilateral nodular hyperplasia); at 5 years 50% had normal blood pressure, 25% had mild hypertension and 25% had moderate to severe hyp ertension. Forty-three patients with either adenoma (APA) or idiopathi c aldosteronism (IHA) received long-term spironolactone treatment. Amo ng them, 13 required the addition of thiazide and/or beta-blockers, wh ile 13 were switched to an amiloride/thiazide combination (+/- beta bl ockers) due to side-effects to spironolactone (gynecomastia 6/20 males , menstrual upset or breast pain in 7/23 females). In group II, 12 pat ients underwent surgery (II adenoma, I primary hyperplasia) with a sim ilar outcome at 3 years as in group I; 25 patients were put on either K canrenoate (II) or Ca++ channel blockers (14) with or without KCI su pplementation; in 8 cases these two drugs were combined according to b lood pressure levels achieved during the follow-up. ACE inhibitors, th iazide, ketanserin, and ketoconazole were given in selected cases. Gyn ecomastia 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 oth er patients with ACTH-dependent MES were all treated initially with de xamethasone (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 h ormonal patterns. Ca++ antagonists have been added in these cases, and K canrenoate substituted for DEX in the AME Type II patient. In concl usion, surgical removal or long term treatment of ME with specific ant agonists or inhibitors may be inadequate to normalize high blood press ure in almost a half of the patients with MES. This could be due, inte r alia, to the persistence of vascular abnormalities, to the coexisten ce of essential hypertension, or to our only partial understanding of the pathophysiology of some of these syndromes (e.g., IHA and AME).