A NEW SUBSET OF MINERALOCORTICOID HYPERTENSION WITH EXCESS OF 21-DEOXYALDOSTERONE AND KELLYS-M1 STEROID - CLINICAL AND MORPHOLOGICAL FINDINGS

Ten cases of adrenal adenomas, one case with unilateral adrenal hyperp lasia, and another case with apparent bilateral are reported, in whom an alternative pathway of aldosterone via 21-deoxyaldosterone is opera tive. They all manifested hypertension, low renin activity, low normal potassium values, as well as high urinary excretion rates of 21-deoxy aldosterone and its related metabolite Kelly's-M1 steroid. In all case s, urinary aldosterone metabolites (aldosterone-18-glucuronide and tet rahydroaldosterone) and aldosterone precursor 18-hydroxycorticosterone levels were normal. Hence, the adrenal lesions give rise to hyper-21- deoxyaldosteronism. 21-Deoxyaldosterone is a weak mineralocorticoid, a nd its elevated production in the presence of normal aldosterone can i nduce a pathological state of hypermineralocorticoidism. Adrenalectomy resulted in normalization of hypertension in six of eight and amelior ation in two of eight cases. Six of seven adenoma cases examined as we ll as the case of unilateral adrenal hyperplasia were sensitive to ACT H. One of the seven adenomas and, as expected, the case with apparent bilateral hyperplasia were angiotensin responsive. Histologically and electron microscopically, the operated adenomas consisted predominantl y of clear cells, characterized by mitochondria with tubulo-vesicular internal structure similar to those of the zona fasciculata (in contra st, our classical Conn's adenoma with normal 21-deoxyaldosterone excre tion exhibited a more heterogenous histological appearance and were, i n terms of ultrastructure, more similar to cells of the zona glomerulo sa). Ultrastructurally and immunocytochemically, the clear cells of 21 -deoxyaldosterone adenomas showed features of both the zona glomerulos a and the zona fasciculata and are, hence, considered to be hybrid cel ls. We conclude that the determination of 21-deoxyaldosterone and Kell y's-M 1 should be considered in the diagnosis of mineralocorticoid-ind uced forms of hypertension, especially when an adrenal adenoma has bee n detected with an imaging procedure.