Aldosterone is Aberrantly Regulated by Various Stimuli in a High Proportion of Patients with Primary Aldosteronism

Abstract

Abstract Context In primary aldosteronism (PA), aldosterone secretion is relatively independent of the renin–angiotensin system, but can be regulated by several other stimuli. Objective To evaluate aldosterone response to several stimuli in a series of patients with PA secondary either to bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Design and setting Prospective cohort study conducted in a university teaching hospital research center. Patients Forty-three patients with confirmed PA and subtyped by adrenal vein sampling (n = 39) were studied, including 11 with BAH, 28 with APA, and 4 with undefined etiology. We also studied 4 other patients with aldosterone and cortisol cosecretion. Interventions We systematically explored aberrant regulation of aldosterone using an in vivo protocol that included the following stimulation tests performed over 3 days under dexamethasone suppression: upright posture, mixed meal, adrenocorticotropin (ACTH) 1-24, gonadotropin-releasing hormone (GnRH), vasopressin, and serotonin R4 agonist. Main outcome measures Positive response was defined as >50% renin or ACTH-independent increase in plasma aldosterone/cortisol concentration following the various stimulation tests. Results Renin-independent aldosterone secretion increased in response to several aberrant stimuli (upright posture, GnRH) in up to 83% of patients with APA or BAH in whom ACTH 1-24 and HT4R agonists also produced aldosterone oversecretion in all patients. The mean significant aberrant responses per patient was similar in BAH (4.6) and in APA (4.0). Conclusions Aldosterone secretion in PA is relatively autonomous from the renin–angiotensin system, but is highly regulated by several other stimuli, which contributes to the large variability of aldosterone levels in PA patients.