The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment Anand Vaidya, 1 Paolo Mulatero, 2 Rene Baudrand, 3 and Gail K. Adler 1 1 Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115; 2 Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Torino, 10126 Torino, Italy; and 3 Program for Adrenal Disorders and Hypertension, Department of Endocrinology, Pontificia Universidad Catolica de Chile, Santiago, 8330074, Chile ORCiD numbers: 0000-0002-0314-9252 (A. Vaidya). ABSTRACT Primary aldosteronism is characterized by aldosterone secretion that is independent of renin and angiotensin II and sodium status. The deleterious effects of primary aldosteronism are mediated by excessive activation of the mineralocorticoid receptor that results in the well-known consequences of volume expansion, hypertension, hypokalemia, and metabolic alkalosis, but it also increases the risk for cardiovascular and kidney disease, as well as death. For decades, the approaches to defining, diagnosing, and treating primary aldosteronism have been relatively constant and generally focused on detecting and treating the more severe presentations of the disease. However, emerging evidence suggests that the prevalence of primary aldosteronism is much greater than previously recognized, and that milder and nonclassical forms of renin-independent aldosterone secretion that impart heightened cardiovascular risk may be common. Public health efforts to prevent aldosterone-mediated end-organ disease will require improved capabilities to diagnose all forms of primary aldosteronism while optimizing the treatment approaches such that the excess risk for cardiovascular and kidney disease is adequately mitigated. In this review, we present a physiologic approach to considering the diagnosis, pathogenesis, and treatment of primary aldosteronism. We review evidence suggesting that primary aldosteronism manifests across a wide spectrum of severity, ranging from mild to overt, that correlates with cardiovascular risk. Furthermore, we review emerging evidence from genetic studies that begin to provide a theoretical explanation for the pathogenesis of primary aldosteronism and a link to its phenotypic severity spectrum and prevalence. Finally, we review human studies that provide insights into the optimal approach toward the treatment of primary aldosteronism. (Endocrine Reviews 39: 1057 – 1088, 2018) A Brief History of Aldosterone and Primary Aldosteronism T homas Addison published his seminal obser- vations in in Disease of the Supra-Renal Capsules (), in which he described a series of patients who almost universally died following a prolonged and progressive illness characterized by fatigue, circulatory collapse, and hyperpigmentation: “The patient, in most of the cases I have seen, has been observed gradually to fall off in general health; he becomes languid and weak, indisposed to either bodily or mental exertion, the pulse small and feeble, or perhaps somewhat large, but excessively soft and com- pressible … and there is occasionally actual vomiting, which in one instance was both urgent and distressing; and it is by no means uncommon for the patient to manifest indications of dis- turbed cerebral circulation. Notwith- standing these unequivocal signs of feeble circulation, anaemia, and gen- eral prostration, neither the most dil- igent inquiry, nor the most careful physical examination, tends to throw the slightest gleam of light upon the ISSN Print: 0163-769X ISSN Online: 1945-7189 Printed: in USA Copyright © 2018 Endocrine Society Received: 13 May 2018 Accepted: 10 August 2018 First Published Online: 15 August 2018 doi: 10.1210/er.2018-00139 https://academic.oup.com/edrv 1057 REVIEW Downloaded from https://academic.oup.com/edrv/article/39/6/1057/5074252 by guest on 21 April 2021
The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment
Apr 20, 2023
Primary aldosteronism is characterized by aldosterone secretion that is independent of renin and angiotensin II and sodium
status. The deleterious effects of primary aldosteronism are mediated by excessive activation of the mineralocorticoid receptor that results in
the well-known consequences of volume expansion, hypertension, hypokalemia, and metabolic alkalosis, but it also increases the risk for
cardiovascular and kidney disease, as well as death. For decades, the approaches to defining, diagnosing, and treating primary aldosteronism
have been relatively constant and generally focused on detecting and treating the more severe presentations of the disease. However,
emerging evidence suggests that the prevalence of primary aldosteronism is much greater than previously recognized, and that milder and
nonclassical forms of renin-independent aldosterone secretion that impart heightened cardiovascular risk may be common.
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Public health efforts to prevent aldosterone-mediated end-organ disease will require improved capabilities to diagnose all forms of primary aldosteronism while optimizing the treatment approaches such that the excess risk for cardiovascular and kidney disease is adequately mitigated. In this review, we present a physiologic approach to considering the diagnosis, pathogenesis, and treatment of primary aldosteronism. We review evidence suggesting that primary aldosteronism manifests across a wide spectrum of severity, ranging from mild to overt, that correlates with cardiovascular risk
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