Endocrine Abstracts

Context: Autonomous cortisol secretion (ACS) has been associated with a higher prevalence of osteoporosis and fragility fractures in several studies. However, the data rely on heterogeneous studies and criteria for osteoporosis screening in this population are still debated.

Objective: To assess the prevalence of fragility fractures and contributing factors in a large cohort of patients with adrenal incidentalomas.

Methods: We reviewed medical records of 1023 patients with adrenal incidentalomas from 1990 to 2019. Of these, 756 patients were selected after exclusion of confounders such as concomitant diseases or treatments, or missing data. Clinically-obtained electronic radiological images closest to the date of clinical evaluation, such as lateral views of spine X-rays or CT thoraco-abdominal scans, were reviewed by two experts blinded to clinical data to screen for asymptomatic morphometric vertebral fractures. Clinical fragility fractures were also recorded. 491 patients had non-secreting (NS) adrenal incidentalomas, 240 had ACS and 25 Cushing Syndrome (CS). Diagnosis of NS and ACS was based on cortisol after 1-mg dexamethasone suppression test (1 mgDST) (<50 and >50 nmol/l, respectively). Biochemical parameters of bone metabolism and hormonal data were recorded.

Results: ACS were older than NS patients (65.5 vs 60.5 years, P<0.001). Prevalence of fragility fractures was different (P=0.021) between groups, respectively 18.9% (NS), 27.1% (ACS) and 32% (CS), with significant difference between NS and ACS (P=0.012). When analyzed separately by sex and menopausal status, this difference remained significant in post-menopausal women (P=0.003), with a prevalence of 16.7% (NS), 28.2% (ACS) and 50% (CS). By contrast, prevalence of fractures was similar in males, even when analysis was adjusted for low testosterone levels (<3 ng/ml). Women with ACS aged ≥65 years reported a 40% prevalence of fragility fractures, as compared with 23.6% in NS (P=0.016). In younger women and in males with cut-off age set at 65 years, prevalence of fractures was similar between groups. Following logistic regression analysis including biochemistries and clinical data of the overall population, fragility fractures were predicted independently by age (OR=1.04, P<0.001) and post-1 mgDST cortisol (OR=2.07, P=0.001). After sex and menopausal status sub-analysis, an independent contributory effect from age (OR=1.07, P<0.001) and 1 mgDST (OR=4.49, P=0.001) remained significant only in post-menopausal women.

Conclusions: Post-menopausal women aged 65 or older with adrenal incidentalomas and ACS showed higher risk of fragility fractures than NS, with ACS likely playing an independent major pathogenetic role.