Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling

Abstract

Primary aldosteronism is classified as aldosterone-producing adenoma (APA), idiopathic hyperaldosteronism (IHA), unilateral adrenal hyperplasia (UAH), primary adrenal hyperplasia (PAH), adrenal cancer, and glucocorticoid-remediable aldosteronism. We describe here 4 cases of primary aldosteronism due to unilateral hyperaldosteronemia, demonstrating unique histopathologic findings, such as unilateral multiple adrenocortical micronodules in the affected adrenals. Thirty-three patients with primary aldosteronism were consecutively admitted; 27 of them were treated by unilateral adrenalectomy. Four of them also had unilateral adrenal hypersecretion of aldosterone by selective adrenal venous sampling and adrenocortical multiple micronodules without an adenoma. These patients had hyporeninemic hyperaldosteronism with normokalemic hypertension. In these patients, furosemide plus upright test failed to increase plasma renin activity (PRA); the ratio of plasma aldosterone concentration (PAC) to PRA at 90 minutes after captopril administration was similar to that in patients with IHA and APA. Aldosterone concentrations were increased in each unilateral adrenal vein, and poorly encapsulated multiple adrenocortical micronodules from 2 to 3 mm in diameter were microscopically detected in the resected adrenal glands. Immunohistochemical analysis of steroidogenic enzymes, including cholesterol side chain cleavage, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 17alpha-hydroxylase, and 11beta-hydroxylase, indicated that the cortical cells within these micronodules were active in aldosterone production, while the non-nodular zona glomerulosa cells were inactive. We conclude that the clinical and pathologic characteristics of our 4 cases with unilateral multiple adrenocortical micronodules (UMN) are distinct from those of APA, IHA, UAH, and PAH. Furthermore, unilateral hyperaldosteronemia induced by UMN may be frequently misdiagnosed, because standard imaging tests, which cannot always detect tiny abnormalities of adrenals, showed "normal adrenal glands" in these patients. Thus, primary aldosteronism due to UMN should be carefully examined for differential diagnosis of each form of hyperaldosteronemia.