Endocrine Abstracts

Background: Steroid profiling by mass spectrometry (MS) provided novel insights into the pathogenesis of adrenocortical tumors and hypercortisolism. The aims of the study were (I) to analyze the steroid profiling by liquid chromatography-tandem MS (LC-MS/MS) in a large cohort of patients with adrenal incidentalomas and (II) to investigate the relationship between steroid profile and clinical outcomes.

Methods: We included 307 patients with mono- and bilateral benign adrenal tumors, after excluding pheochromocytoma, primary hyperaldosteronism, late-onset congenital adrenal hyperplasia, and Cushing’s syndrome. We classified patients as non-secreting (NS) or with subclinical hypercortisolism (SH) according to cortisol after 1 mg-dexamethasone suppression test (DST) (≤50 and >50 nmol/L, respectively). LC-MS/MS serum steroid profiling included cortisol, cortisone, 21-deoxycortisol, 11-deoxycortisol, 11-deoxycorticosterone, corticosterone, progesterone, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEA), and testosterone. Steroid profile was assessed in basal condition in all patients, after 1 mg-DST (n=153), and after stimulation with 1-24ACTH 250 μg (n=91). Data at follow-up (mean 39.6 months) were available for 207 patients.

Results: Basal steroid profiling revealed increased levels of cortisol (P=0.001) and 11-deoxycortisol (P=0.002), and lower DHEA (P<0.001) and androstenedione (P<0.001) in patients with SH vs NS. Comparable results were obtained in adenoma SH vs NS (n=175) and hyperplasia SH vs NS (n=132). 1-24ACTH stimulation revealed significant higher levels of all steroids, except for 21-deoxycortisol and androgens, in SH vs NS. Additionally, higher levels of 21-deoxycortisol (P=0.006) and lower levels of DHEA (P=0.014) and androstenedione (P=0.034) were observed in patients with adenoma associated with SH vs NS. Steroid profiling after 1 mg-DST revealed higher levels of cortisone, 11- deoxycortisol, and corticosterone (P<0.001 for all) in SH vs NS. Moreover, androgens were significantly lower in patients with SH. Logistic regression analysis showed that increasing corticosterone levels (Odds Ratio (OR) 1.122, 95% Confidence Interval (CI) 1.006–1.251, P=0.038) and reduced DHEA levels (OR 0.474, 95% CI 0.241–0.931, P=0.030) were associated with cardiovascular events, among all potential contributing factors. Increasing levels of 11-deoxycortisol were significantly associated with diabetes/impaired glucose tolerance (OR 3.002, 95% CI 1.143–7.889, P=0.026), with an independent contribution of age (P=0.002), BMI (P=0.039) and family history of diabetes (0.001). Patients with NS tumors who developed SH during follow-up (24/207, 11.6%) had basal lower DHEA, androstenedione, and ACTH levels, and showed higher cortisol after 1 mg-DST and larger adrenal tumors.

Conclusion: Patients with SH have a specific steroid profile with potential implications on cardiovascular and metabolic alterations.