Long-Term Follow-Up of Patients With Elevated Aldosterone-to-Renin Ratio but Negative Confirmatory Test: The Progression of Primary Aldosteronism Phenotypes

Abstract

BACKGROUND: About 10% of patients with arterial hypertension have a positive screening test for primary aldosteronism (PA) and 50% to 70% of them have a negative confirmatory test: the appropriate follow-up of these patients is currently unknown. We investigate the incidence of PA in patients with previous negative confirmatory testing, after at least a 2-year follow-up. METHODS: One hundred eighty-four patients with a previously elevated aldosterone-to-renin ratio followed by a negative confirmatory test were recruited in 2 hypertension centers (Torino and Munich). We repeated the screening test for PA and, if positive, the confirmatory test (seated saline infusion test or captopril challenge test). Primary end point of the study was the incidence of newly diagnosed overt PA, as defined by a positive confirmatory test. RESULTS: After a mean follow-up of 5 years, 20% of patients developed overt PA. When subtype diagnosis was offered systematically, one-third of patients displayed unilateral PA. Patients who developed PA showed worsening of blood pressure control and a higher rate of cardiac organ damage, despite similar implementation of antihypertensive therapy, compared with patients without PA. A mild progression of autonomous aldosterone secretion was evident even in patients without confirmed PA but with relatively stable control of blood pressure levels over time. CONCLUSIONS: About one-fifth of patients with a negative confirmatory test develop overt PA over time. A clinical follow-up of patients with a negative confirmatory test is advisable, along with the repetition of PA investigation, primarily in patients with worsening of blood pressure control.

The Spectrum from Overt Primary Aldosteronism to Mild Dysregulated Aldosterone Production in Incidentally Discovered Adrenocortical Adenomas

“…This was achieved even without the use of confirmatory testing, which might have reduced the number of patients who could potentially benefit from targeted therapy due to stricter thresholds. 3,38,39 Additionally, PAC was measured using immunoassay, which has known limitations compared to LC-MS/MS, 40 however, urinary aldosterone was measured using LC-MS/MS, and the results behaved similarly.…”

“…It is currently described that PA exists across a continuum of severity, from overt cases with advanced hypertension and/or hypokalemia, to milder forms that include individuals with prehypertension or even normotension. 3–5 The clinical relevance of this continuum is highlighted in overt PA, a condition known to have substantially higher risk for adverse cardiovascular outcomes; 6,7 however, it is increasingly recognized that patients with milder forms of PA also have a substantially higher risk for developing progressive cardiovascular disease, such as myocardial infarction, stroke, atrial fibrillation and left ventricular hypertrophy. 4,8–11 Importantly, recognizing PA and implementing targeted therapy with mineralocorticoid receptor (MR) antagonists or surgery can mitigate these adverse cardiovascular outcomes in a real-life scenario.…”