Changes in Glucose Metabolism after Adrenalectomy or Treatment with a Mineralocorticoid Receptor Antagonist for Primary Aldosteronism

Abstract

Background: Data on the effects of excess aldosterone on glucose metabolism are inconsistent. This study compared the changes in glucose metabolism in patients with primary aldosteronism (PA) after adrenalectomy or treatment with a mineralocorticoid receptor antagonist (MRA).

Methods: Overall, 241 patients were enrolled; 153 underwent adrenalectomy and 88 received an MRA. Fasting glucose, homeostatic model assessment of insulin resistance (HOMA-IR), and homeostatic model assessment of β-cell function (HOMA-β) were compared between the treatment groups after 1 year. Plasma aldosterone concentration (PAC) and factors determining HOMA-IR and PAC were evaluated.

Results: No baseline differences were observed between the groups. Fasting insulin, HOMA-IR, and HOMA-β increased in both groups and there were no significant differences in fasting glucose following treatment. Multiple regression analysis showed associations between PAC and HOMA-IR (β=0.172, P=0.017) after treatment. Treatment with spironolactone was the only risk factor associated with PAC >30 ng/dL (odds ratio, 5.2; 95% confidence interval [CI], 2.7 to 10; P<0.001) and conferred a 2.48-fold risk of insulin resistance after 1 year compared with surgery (95% CI, 1.3 to 4.8; P=0.007).

Conclusion: Spironolactone treatment might increase insulin resistance in patients with PA. This strengthened the current recommendation that adrenalectomy is the preferred strategy for patient with positive lateralization test. Achieving a post-treatment PAC of <30 ng/dL for improved insulin sensitivity may be appropriate.

Keywords: Adrenalectomy; Hyperaldosteronism; Insulin resistance; Spironolactone.

Fig. 1

Flow chart of study design, exclusion criteria, and allocation of patients. UNL, upper normal limit.

Fig. 2

Association between the aldosterone levels and homeostasis model assessment of insulin resistance (HOMA-IR). Generalized additive model showing a positive nonlinear relationship between log (HOMA-IR after treatment) against log (aldosterone after treatment) after adjusting for age, sex, serum potassium, serum creatinine, and systolic blood pressure. Log (plasma aldosterone concentration=30 [μg/L])=1.47 was an independent factor predicting increased HOMA-IR after treatment.