Letter to the Editor: “Impaired Glucose Metabolism in Primary Aldosteronism Is Associated With Cortisol Cosecretion”

Primary aldosteronism (PA) is not an uncommon diagnosis in routine endocrine practice. About half of patients have PA due to autonomous production of aldosterone from adrenal nodule(s), and current guidelines recommend curative adrenalectomy in this cohort to improve long-term vascular outcomes (1). However, sometimes patients instead elect to receive pharmacological therapy that includes a mineralocorticoid receptor antagonist (MRA). In this regard, the results of the study by Gerards et al (2) may further strengthen our discussions in the clinic why adrenalectomy is the procedure of choice for those who have unilateral PA. In a carefully selected cohort of patients, the authors found modest but significant increases in the frequency of type 2 diabetes and metabolic parameters indicative of insulin resistance in patients who had concomitant PA and biochemical evidence of autonomous cortisol production compared with the patients without PA or the patients with PA and without biochemical hypercortisolism. The results were adjusted for multiple covariates including age, sex, and body mass index. However, upon further review of the study design we would like to inquire if in their analyses the authors considered prevalence and type of MRA therapy and associated use of beta-blockers and thiazide diuretics in the studied patients.

The MRA therapy in the PA patients involves use of either spironolactone or eplerenone. A recent meta-analysis of 12 randomized controlled studies showed that spironolactone in patients without or with diabetes mellitus may cause or worsen dysglycemia, respectively, manifested by significant increases in hemoglobin A1c while eplerenone effects on glucose metabolism are neutral (3). Furthermore, in a 6-week prospective study in hypertensive patients, researchers demonstrated that eplerenone has neutral effects on glucose metabolism (4) and, in the animal model, spironolactone but not eplerenone use was associated with the development of impaired glucose tolerance (5). Multiple antihypertensive agents are frequently required to control blood pressure in PA patients. Of interest for this discussion, several prospective cohort studies demonstrated that thiazide diuretic and beta-blocker use is associated with increased risk of a new diagnosis of type 2 diabetes (6, 7).

Therefore, in contrast to the authors’ conclusions that biochemical hypercortisolism can explain dysglycemia in the PA patients, one could instead hypothesize that the modest glycemic derangements observed in the subgroup of the patients with coexistent autonomous cortisol production could have been due to higher frequency of prodiabetogenic antihypertensive medication use. There is no question that autonomous cortisol production is highly prevalent in the PA patients. What is not clear is whether this process has any significant metabolic implications for the PA patients.

Abbreviations

Abbreviations
 
• PA

  primary aldosteronism

 
• MRA

  mineralocorticoid receptor antagonist

Acknowledgments

Author Contributions: All authors had access to the data and a role in writing the manuscript.

Disclosure Summary: The authors declare no conflict of interest.