Endocrine Abstracts

Introduction

Irisin is a molecule secreted from skeletal muscle and contributes to maintenance of metabolic homeostasis leading to increased energy expenditure and reducing the risk of obesity and diabetes. Literature data suggest that patients with Cushing disease have lower irisin values than controls and remission of hypercortisolism increases these values. Moreover, other plasma inflammation markers implicated in the pathogenesis of atherosclerosis, including TNF-alpha and IL-6, are increased in Cushing’s syndrome patients. Few data are available in mild autonomous cortisol secretion (MACS) patients. In this randomized study we aimed to evaluate the effects of adrenalectomy on circulating irisin, IL-6 and TNF-a levels in patients with adrenal incidentaloma (AI) and MACS.

Methods

Among 626 AI patients (referred to 3 Italian Centers between 06/2016 and 02/2020), according to the inclusion criteria, we consecutively enrolled 61 patients (45 F) with MACS (cortisol level after 1mg overnight dexamethasone suppression test, 1 mgDST, between 1.8 and 5 µg/dl). Patients were randomized in two groups: surgery (Group 1, n = 29) or conservative follow-up (Group 2, n = 32). Three patients from Group 1 withdrew their consent to surgery. Irisine, TNF-alpha, IL-6 levels, anthropometric, and glyco-metabolic parameters were evaluated at baseline and after 6 months. The study is ongoing.

Results

So far, 40 patients (15 in Group 1 and 25 in Group 2, mean age 64.4 ± 10.4 years, adenoma diameter 2.8 ± 0.7 cm, 1mgDST 3.3 ± 1.6 µg/dl) have completed the 6 months follow-up. At baseline the two groups were comparable for clinical and biochemical characteristics. After 6 months we found that only in group 1 irisin levels increased over time (13.1 ± 1.8 ng/ml at baseline vs 26.2 ± 15 ng/ml at 6 months, P < 0.05) whereas TNF-alpha and IL-6 levels did not change in both groups. At baseline, TNF-alpha and IL-6 levels were correlated to HOMA-index levels (r = 0.408, P = 0.015, R = 0.425, P = 0.011, respectively), that, in turn, significantly correlated with BMI and waist circumference. The TNF-alpha levels were also correlated to the fibrinogen levels (r = 0.360, P = 0.031). We did not find any correlation between TNF-alpha and IL-6 levels and parameters of cortisol secretion (1 mgDST, ACTH, urinary free cortisol/cortisone and midnight salivary cortisol levels). Unexpectedly, we found a strong positive correlation between irisin levels and 1 mgDST (r = 0.625, P = 0.001), we suppose for a mechanism of peripheral resistance, but not with other metabolic parameters.

Conclusion

These preliminary data suggest that, in MACS-patients, irisin levels increases after surgery, whereas they remain steady after a conservative follow-up.

Funding

Supported By Italian Ministry of Health. RF-2013-02356606 Grant.