Endocrine Abstracts

Background: The majority of adrenal incidentalomas (AIs) are benign non-functioning adrenocortical adenomas (NFAIs), yet not clinically silent. Possible autonomous cortisol secretion (PACS) can also be diagnosed in up to 50% of patients. Endocannabinoids (ECs) have recently been studied regarding their role in the hypothalamo-pituitary-adrenocortical (HPA) axis; however, data are scarce in humans.

Aim: We aimed to assess hair EC [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)] levels in patients with AIs compared to controls and their association with the hormone profile of these patients.

Methods: Forty-four patients diagnosed with AIs (32 NFAIs and 12 PACS) and 44 controls (without AIs in computerized tomography), referred to the Endocrinology Unit of the 1st Department of Internal Medicine of Laikon Hospital between June 2020 and July 2021, were recruited. Patients with serum cortisol (F) levels between 1.8 and 5 μg/dl post 1mg dexamethasone suppression test (1mg-DST) were classified in PACS group, whereas those with F levels < 1.8 μg/dl in NFAI group. Basal (8:00 am) F, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate (DHEA-S) as well as 24-h urinary free cortisol (UFC) were also analysed. Hair samples were collected according to Society of Hair Testing guidelines and EC levels were measured by liquid chromatography tandem-mass spectrometry. Statistical analysis was conducted using SPSS version 28.

Results: The age, sex and body mass index as well as the prevalence of hypertension, dyslipidemia, diabetes mellitus type 2 and bone disease did not differ significantly between the groups. Significantly decreased hair AEA and 2-AG levels were found in patients with AIs compared to controls (P<0.001 and P=0.002 respectively) as well as between NFAI or PACS and controls (P<0.001 or P=0.002 and P=0.038 or P=0.02 respectively). Among the AI patients, EC levels were found lower in PACS group compared to NFAI, although not statistically significantly. AEA hair levels were negatively correlated with F levels post 1 mg-DST (r_s=-0.257, P=0.033), but not with F, ACTH, UFC or DHEA-S levels.

Conclusion: Data regarding the interaction between glucocorticoids (GCs) and ECs are scarce, contradictory and analysed mainly in animal models. In humans it seems that the chronic exposure to GCs has an inhibitory effect on the circulating EC levels. Our data showed that patients with AIs presented lower EC levels compared to controls enhancing the hypothesis of the suppressive effect of chronic hypercortisolism on hair EC levels. The role of ECs on HPA axis merits a more thorough analysis in larger human studies.