Endocrine Abstracts

JOINT681

Background: Mild autonomous cortisol secretion (MACS) as well as non-functional adrenal incidentalomas (NFAI) are associated with increased metabolic and cardiovascular risk suggesting a subtle secretion of cortisol or of other precursors of steroidogenesis.

Aim: To investigate steroid metabolites levels in patients with MACS and NFAI benign adrenal tumours as well as in adrenocortical carcinomas (ACC). Controls were defined as patients with normal adrenals on imaging.

Methods: Liquid chromatography–tandem mass spectrometry (LCMS) was used for the steroidomics analysis of several steroid precursors [cortisol (F), corticosterone (B,CORT), 11-deoxycorticosterone (DOC), 11-deoxycortisol (11-DOC, compoundS), 21-deoxycortisol (21-DOF), aldosterone (ALDO), testosterone (T), dihydrotestosterone (DHT), androstenedione (A4), androsterone (AN), dehydroepiandrosterone (DHEA), dehydroepiandrosterone Sulfate (DHEAS), progesterone (P4), 17-hydroxyprogesterone (17-OHP4), pregnenolone (P5), 17-hydroxypregnenolone (17-OHP5), estradiol (E2), estrone (E1)] in the blood of 35 patients. The categorisation of patients in functional or NFAI was based on functional hormonal blood tests [1 mg overnight dexamethasone suppression test (ODST)] based on current guidelines. All ACC cases were confirmed histopathologically.

Results: A total of 29 patients (8 males) with adrenal tumors [(n=17 with NFAI, n=8 with MACS and n=4 with ACC] and 6 controls were included. Tumor size was significantly higher in ACC compared to NFAI and MACS patients. Urinary-free cortisol (UFC) levels were 5-fold higher in ACC and 3-fold higher in MACS compared to NFAI patients (although within normal range for MACS) LCMS analysis showed that all the median blood steroid hormones levels were significantly higher (P<0.05) in ACC patients compared with NFAI, MACS and control patients except for aldosterone levels. Regarding patients with benign tumors, median levels of baseline morning cortisol, corticosterone, 11-deoxycorticosterone and 21-deoxycortisol were significantly higher in MACS compared with NFAI (P=0.04, P=0.03, P=0.047, P=0.043 respectively). Baseline median levels of cortisol, corticosterone, 11-deoxycorticosterone and progesterone levels were significantly higher in MACS compared with controls (P=0.037, P=0.042, P=0.039, P=0.023 respectively). Baseline median levels of 11-deoxycorticosterone were significantly higher in NFAI compared with controls (P=0.01) whereas progesterone and 17-OH progesterone were significantly lower in NFAI compared with controls (P=0.002, P=0.04). Among comorbidities hypertension, hyperlipidemia and diabetes mellitus prevalence was higher in patients with adrenal tumours compared to controls as well as between NFAI and controls.

Conclusions: All steroid hormones levels were significantly higher in ACC patients compared to patients with MACS and NFAI. Precursors such as 11-deoxycorticosterone, and 21-deoxycortisol could play a supplementary role to the routine hormones profile for the distinction of NFAI from controls or MACS.