Obesity has been shown to correlate directly with circulating aldosterone levels and urinary aldosterone excretion in normotensive and hypertensive individuals without primary aldosteronism (PA). This relationship may be bi-directional, though it is probably not symmetrical. Activation of the mineralocorticoid receptor in adipocytes may cause expansion of visceral fat mass. Conversely, adipocytes have been shown to augment the adrenal production of aldosterone by their release of aldosterone secretagogues-leptin, C1q/TNF-related proteins 1, and resistin-into the circulation. Patients with PA are more obese (idiopathic hyperaldosteronism>aldosterone-producing adenoma) than those with essential or no hypertension (women>men). The stronger association of obesity with idiopathic hyperaldosteronism than with the more metabolically severe unilateral PA, and the reductions in aldosterone levels after weight loss, suggest a substantive role for adipocytes in circulating aldosterone levels. A 2-sample Mendelian randomization analysis suggested that peri-renal adipose tissue, a form of visceral adipose tissue encompassing the adrenal glands, was causally linked to idiopathic hyperaldosteronism but not to other forms of hypertension. These observations support the speculation that at least a portion of idiopathic hyperaldosteronism cases represent adipocyte-driven hyperaldosteronism that might be effectively treated by weight loss. This review will provide the trans-disciplinary rationale for the hypothesis supporting a causal relationship between obesity and idiopathic hyperaldosteronism. This unproven hypothesis is eminently testable given the powerful pharmacological and surgical weight loss strategies currently available.
Keywords: adenoma; humans; hypertension; leptin; obesity.