The Role of Aldosterone in Detecting Resistance-Driven Hypoaldosteronism and Deficit-Driven Hypoaldosteronism

Sep 30, 2026

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Hypoaldosteronism is divided into aldosterone deficit (Aldo-D) and aldosterone/mineralocorticoid resistance (Aldo-R) according to etiopathogenic mechanisms, but reliable methods to distinguish these subtypes are lacking. A retrospective analysis of eighty-four cases assessed whether plasma aldosterone (PAC) measured during hyperkalemia or hyperreninemia can identify each subtype. PAC accuracy was limited overall; however, extreme PAC thresholds suggested Aldo-D (≤60 pg/mL) or Aldo-R (≥200 pg/mL) despite overlap in intermediate values.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

Background/Objectives

Methods

Results

Conclusions

1. Introduction

Article The Role of Aldosterone in Detecting Resistance-Driven Hypoaldosteronism and Deficit-Driven Hypoaldosteronism Jorge Gabriel Ruiz-Sánchez 1, *, Alfonso Luis Calle-Pascual 2,3,4, Miguel Ángel Rubio-Herrera 2,3, Paz De Miguel Novoa 2,3, Emilia Gómez-Hoyos 5 and Isabelle Runkle 2,3 Academic Editor: Maria Elisabeth Street Received: 17 November 2025 Revised: 19 December 2025 Accepted: 24 December 2025 Published: 27 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Servicio de Endocrinología y Nutrición, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain 2 Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain 3 Servicio de Endocrinología y Nutrición, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, 28040 Madrid, Spain 4 Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain 5 Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, 47003 Valladolid, Spain * Correspondence: jorgeg.ruiz@quironsalud.es Abstract Background/Objectives: Hypoaldosteronism is classified into “aldosterone deficit”(AldoD) and “aldosterone/mineralocorticoid resistance”(Aldo-R) based on etiopathogenic mechanisms. This distinction could be useful for guiding the treatment. However, no reliable methods have been established to differentiate these subtypes. We first aimed to assess whether aldosterone levels could help identify them when assessed in the setting of hyperkalemia or hyperreninemia. Methods: We conducted a retrospective analysis of eighty-four cases of hypoaldosteronism. Aldo-D and Aldo-R classification was based on the presence of clinical factors associated with aldosterone deficit and mineralocorticoid resistance, respectively. The accuracy of plasma aldosterone (PAC) to identify each type of hypoaldosteronism individually was evaluated using AUC-ROC analysis. Results: Aldo-D was identified in 66 (78.6%), and Aldo-R in 41 (48.8%) cases. Factors related to both subtypes were observed in forty-seven (56%) cases. AUC-ROC analysis of PAC measured during hyperkalemia showed low accuracy for detecting either subtype. During hyperreninemia, PAC accuracy was adequate for identifying Aldo-D but unsatisfactory for Aldo-R. Nevertheless, a PAC ≤ 60 pg/mL (6 ng/dL, ~166 pmol/L) during hyperkalemia and hyperreninemia yielded positive predictive values (PPV) of 94% and 100%, respectively, for Aldo-D, while a PAC value > 160 pg/mL (~443 pmol/L), particularly ≥ 200 pg/mL (20 ng/dL, ~550 pmol/L) in either condition had a PPV of 100% for Aldo-R. Conclusions: Although overall diagnostic accuracy was limited, extreme low and high PAC values (≤ 60 pg/mL or ≥ 200 pg/mL) may be suggestive of Aldo-D or Aldo-R, respectively, while intermediate values remain difficult to interpret due to substantial overlap. Keywords: hypoaldosteronism; isolated hypoaldosteronism; aldosterone; hyperreninemia; hyperkalemia 1. Introduction Aldosterone, the most important mineralocorticoid in humans, is synthesized in the adrenal gland’s zona glomerulosa. Its production is primarily regulated by the following two stimuli: angiotensin-II (via the renin–angiotensin–aldosterone system RAAS) and the blood potassium concentration ([K+]) [1] . Elevations in renin, and consequently, angiotensin-II (AngII) levels lead to an increase in adrenal aldosterone secretion. Additionally, a decrease in the former leads to a descent in the latter. Elevated [K+](hyperkalemia) enhances aldosterone production, whereas low [K+](hypokalemia) suppresses it. Furthermore, adrenocorticotropic hormone (ACTH) also plays a role in aldosterone pro

FAQs

How are hypoaldosteronism subtypes classified in this study?

Hypoaldosteronism is classified into aldosterone deficit (Aldo-D) and aldosterone/mineralocorticoid resistance (Aldo-R) based on underlying etiopathogenic mechanisms and associated clinical factors.

What was evaluated to differentiate Aldo-D and Aldo-R?

The study evaluated the accuracy of plasma aldosterone (PAC) to identify each subtype, using AUC-ROC analysis when assessed during hyperkalemia or hyperreninemia.

Which plasma aldosterone thresholds were most informative?

During hyperkalemia and hyperreninemia, PAC ≤ 60 pg/mL supported identifying Aldo-D with high PPV, while PAC > 160 pg/mL—especially ≥ 200 pg/mL—yielded PPV of 100% for Aldo-R in either condition.

Sep 30, 2026

Upload by jay