Impaired Glucose Metabolism in Primary Aldosteronism Is Associated With Cortisol Cosecretion

Abstract

CONTEXT Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and metabolic risks. Recent studies report glucocorticoid co-secretion as a relevant phenotype of PA, which could contribute to associated risks, including type 2 diabetes mellitus (T2DM). The relationship between autonomous cortisol secretion (ACS) and glucose metabolism in PA has not been investigated. OBJECTIVE To evaluate the prevalence of impaired glucose homeostasis in PA patients according to cortisol co-secretion. METHODS We performed oral-glucose-tolerance-tests (OGTT) and complete testing for hypercortisolism (1mg-dexamethasone-suppression-test (DST), late-night-salivary-cortisol (LNC), 24hour-urinary-free-cortisol (UFC)) in 161 newly diagnosed PA patients of the German Conn Registry. 76 of 161 patients were reevaluated at follow-up. We compared our results to a population-based sample from the KORA-F4 study matched to the PA participants (3:1) by sex, age, and BMI. RESULTS At the time of diagnosis, 125 patients (77.6%) had a pathological response in at least one of the Cushing screening tests; T2DM was diagnosed in 6.4% of these 125 cases. Patients with pathological DST exhibited significantly higher 2h plasma glucose in OGTT and were significantly more often diagnosed with T2DM than patients with normal DST (20% vs. 0.8%, p<0.0001) and matched controls from the KORA study (20.6% vs. 5.9%.; p=0.022). PA patients without ACS tended to have higher homeostatic-model-assessmentof-insulin-resistance (HOMA-IR) than KORA control subjects (p=0.05). CONCLUSION ACS appears frequently in PA patients and is associated with impaired glucose metabolism, which could increase the risk of T2DM. PA itself seems to enhance insulin resistance.

Clinical characterization of patients with primary aldosteronism plus subclinical Cushing’s syndrome

“…The proportion of DM patients increased significantly in the PASCS group than in the PA group (p < 0.05), which is in line with a previous study that described abnormal glucose metabolism in PA patients with cortisol hypersecretion [29]. Hyperaldosteronism found in patients with PA also induces abnormal glucose metabolism [21][22][23], although being less intense as compared with hypercortisolism found in patients with SCS.…”

In situ metabolomics of aldosterone-producing adenomas

“…For example, an inverse correlation of 24-hour urinary free cortisol and the intensity of 18-oxocortisol might be due to the abundance of CYP11B1, which promotes cortisol production in APA tissues. Two previous studies revealed that glucocorticoid cosecretion in APAs is frequently found, and several surrogate parameters of metabolic risk were correlated with glucocorticoid secretion, which suggested the concept of "Connshing" syndrome (15,38). Our findings showed the importance of distribution of CYP11B1 in tumor tissues, not that of CYP11B2, with respect to clinical outcome and provided new insights into this concept.…”

Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism

“…Interestingly, the DM prevalence and FPG levels were significantly decreased after ADX in PA patients without SH. This is in contrast to the recent study [28], which showed parameters of glucose metabolism did not improve at follow-up. However, this study included only 76 PA patients (25 patients after ADX and 48 patients after MRA therapy).…”

“…One further mechanism underlying the impairment in glucose metabolism in PA is glucocorticoid co-secretion. Although recent studies showed that higher prevalence of DM in PA patients might be associated mainly with SH [27,28], our result showed PA patients without SH, and thus with aldosterone excess alone, had a higher prevalence of DM than do sex-, age-, and BMI-matched controls. Interestingly, the DM prevalence and FPG levels were significantly decreased after ADX in PA patients without SH.…”

“…Third, findings regarding parameters to assess glucose metabolism in PA were not fully consistent [16,[21][22][23][24][25][26]. Fourth, recent studies showed that possible cortisol co-secretion rather than only aldosterone excess itself could contribute to the impairment of glucose metabolism in patients with PA [27,28]. Finally, comparisons of the effects of adrenalectomy (ADX) and mineralocorticoid receptor antagonist (MRA) therapy on glucose metabolism in PA have only sparsely been studied.…”