Evolution of the Primary Aldosteronism Syndrome: Updating the Approach

Abstract

Context: New approaches are needed to address the evolution of the primary aldosteronism syndrome and to increase its recognition. Herein, we review evidence indicating that primary aldosteronism is a prevalent syndrome that is mostly unrecognized, and present a pragmatic and pathophysiology-based approach to improve diagnosis and treatment.

Methods: Evidence was gathered from published guidelines and studies identified from PubMed by searching for primary aldosteronism, aldosterone, renin, and hypertension. This evidence was supplemented by the authors' personal knowledge, research experience, and clinical encounters in primary aldosteronism.

Interpretation of evidence: Renin-independent aldosterone production is a prevalent phenotype that is diagnosed as primary aldosteronism when severe in magnitude, but is largely unrecognized when milder in severity. Renin-independent aldosterone production can be detected in normotensive and hypertensive individuals, and the magnitude of this biochemical phenotype parallels the magnitude of blood pressure elevation, the risk for incident hypertension and cardiovascular disease, and the likelihood and magnitude of blood pressure reduction with mineralocorticoid receptor antagonist therapy. Expansion of the indications to screen for primary aldosteronism, combined with the use of a pathophysiology-based approach that emphasizes inappropriate aldosterone production in the context of renin suppression, will substantially increase the diagnostic and therapeutic yields for primary aldosteronism.

Conclusions: The landscape of primary aldosteronism has evolved to recognize that it is a prevalent syndrome of renin-independent aldosterone production that contributes to the pathogenesis of hypertension and cardiovascular disease. Expanding screening indications and simplifying the diagnostic approach will enable implementation of targeted treatment for primary aldosteronism.

Keywords: adrenal; aldosterone; hypertension; primary aldosteronism; renin.

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Figures

Figure 1.

Simplified diagnostic algorithm for primary aldosteronism. *There is no uniform definition for suppressed renin. A suppressed, or very low, plasma renin activity or renin concentration is necessary to confirm renin-independent aldosteronism that characterizes primary aldosteronism. A suppressed renin is defined as a plasma renin activity of less than 0.6 ng/mL/h, although a more liberal definition of less than 1.0 ng/mL/h can be used. Alternatively, a renin concentration of less than 5 mU/L is considered suppressed, although a more liberal definition of less than 8.2 mU/L can be used. #The most recommended and widely used dynamic confirmatory tests include the oral sodium suppression test, the seated intravenous saline suppression test, the fludrocortisone suppression test, and the captopril challenge test. &Therapeutic doses of mineralocorticoid receptor antagonists and/or epithelial sodium channel inhibitors can induce an increase in renin in patients with primary aldosteronism. Less commonly, high doses of loop diuretics may induce this increase in renin as well. Rarely, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can similarly increase renin in patients with primary aldosteronism. When the pretest probability for primary aldosteronism is reasonably high, a medication washout for 4 weeks, followed by repeat renin and aldosterone measurement, can be conducted to assess the true renin phenotype. AVS, adrenal venous sampling; MR, mineralocorticoid receptor.