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

## TL;DR

The study explores how aldosterone levels can help distinguish between two types of hypoaldosteronism, but finds that only extreme levels are reliable indicators.

## Contribution

The study introduces specific aldosterone thresholds during hyperkalemia and hyperreninemia to differentiate hypoaldosteronism subtypes with high predictive accuracy.

## Key findings

- Aldosterone levels ≤ 60 pg/mL during hyperkalemia and hyperreninemia suggest Aldo-D with 94% and 100% PPV.
- Aldosterone levels ≥ 200 pg/mL in either condition indicate Aldo-R with 100% PPV.
- Intermediate aldosterone levels have limited diagnostic value due to overlap between subtypes.

## Abstract

Background/Objectives: Hypoaldosteronism is classified into “aldosterone deficit” (Aldo-D) 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.