Endocrine Abstracts

Purpose: To evaluate differences in the prevalence of autonomous cortisol secretion (ACS) and related comorbidities between patients with unilateral and bilateral adrenal incidentalomas (AI).

Methods: Seven Spanish institutions participated in this institutional review board-approved retrospective study for patients with AI. 342 patients with one or more AI ≥ 1 cm evaluated by participating physicians between 2001 and 2019 were subject to inclusion. Patients with adrenal lesion detected in the study of extension of an extra-adrenal cancer, with predisposing adrenal hereditary syndromes, manifest functioning AI or missing values in the 1mg dexamethasone suppression test (DST) were excluded. ACS was defined as lack of cortisol suppression after DST in the absence of Cushing Syndrome data. Different cortisol DST thresholds were evaluated: 1.8, 3.0, and 5.0 µg/dl. Diabetes, hypertension, dyslipidemia, cardiovascular and cerebrovascular disease, and obesity were considered ACS related comorbidities.

Results: A total of 256 patients (155 females, 60.6%) were enrolled in the study. 209 (81.6%) had unilateral and 47 (18.4%) bilateral AI. Prevalence of ACS using 1.8 µg/dl, 3.0 µg/dl and 5.0 µg/dl DST threshold was 40.6%, 18.8% and 9.4%, respectively. The prevalence of ACS was significantly higher for bilateral AI (3.0 µg/dl) (31.9% vs 15.8%, P = 0.010). Bilateral ACS AI presented higher risk of diabetes vs unilateral ACS AI (53.3 vs 18.2%, P = 0.013) (3.0 µg/dl) and of obesity (71.4% vs 29.4%, P = 0.058) (5.0 µg/dl). ACS (1.8 µg/dl) was associated with diabetes (OR = 1.8, 95% CI = 1.01–3.13) and cerebrovascular disease (5.0 µg/dl) (OR = 5.3, 95% CI = 1.24–22.78) but not with other comorbidities regardless of DST threshold. Patients with ACS (1.8 µg/dl) had lower DHEAS (54.9 vs 121.7 µg/dl, P = 0.009) and ACTH levels (13.9 vs 21.8 pg/ml, P = 0.001); higher 24-hour urinary free cortisol (77.5 vs 45.3 µg/24 h, P = 0.056) and were larger (25.0 vs 20.0 mm, P = 0.002). Tumor size was negatively correlated with DHEAS (r₂ = −0.16, P = 0.051); and positively with DST (r₂ = 0.18, P = 0.014). However, no analytical or radiological differences were found between bilateral and unilateral AI (P > 0.05), except for DHEAS (162.0 vs 78.6 µg/dl, P = 0.009). During follow-up (mean = 57.9 months), 6 (6.7%) AI grew (>10 mm); 3 (2.0%) non-functioning AI developed ACS (1.8 µg/dl); and 18.4% developed new comorbidities, being significantly more frequent in patients with ACS (1.8 µg/dl) (28.9% in ACS vs 11.2% in non-functioning, P < 0.001). Bilaterality was not associated with tumor growth, or development of ACS or comorbidities.

Conclusion: We found higher prevalence of ACS in bilateral compared to unilateral AI, and an increased risk of diabetes and obesity in AI, but not of growth or development of new comorbidities during follow-up.