Endocrine Abstracts

Purpose

To assess the risk of developing hypercortisolism and/or tumor growth in non-functioning adrenal incidentalomas (NFAIs) during follow-up.

Methods

Seven Spanish institutions participated in this retrospective study for patients with AIs. 1097 patients with one or more AIs ≥ 1 cm evaluated by participating physicians between 2013 and 2020 were subject to inclusion. Patients with missing values in the overnight 1 mg-dexamethasone suppression test (DST) (n = 63); with pheochromocytoma (n = 7); primary aldosteronism (n = 26); autonomous cortisol secretion (ACS) (n = 337) overt Cushing syndrome (CS)(n = 10); or adrenal carcinoma (n = 3), were excluded. ACS was defined as a value >1.8 µg/dl after DST without specific data of CS. Tumor growth was defined as an increase in tumor maximum diameter >20% from baseline; and of at least 5 mm.

Results

654 patients with NFAIs were included. Mean age was 62.1 ± 10.8; and 56% (n = 368) were women. At presentation, median tumor size was 19.3 ± 9.8 mm; 130 patients (20.1%) had bilateral tumours and the median cortisol post-DST level was 1.1 µg/dl (0.4 - 1.8). Of the 654 subjects, tumor diameter and DST were re-evaluated during follow-up in 410 and 364 patients, respectively. After a median follow-up of 26.4 [IQR 10.6 - 50.6] months, 40 out of 364 patients with NFAIs (11%) developed ACS; and none developed overt CS. The risk for developing ACS during follow-up was higher for patients with higher cortisol post-DST values (HR 4.1 for each µg/dl, 95% CI 1.4 - 11.7), older age (HR 1.04 for each year, 95% CI 1.01 - 1.08); and smaller tumor size (HR 0.92 for each mm, 95% CI 0.86 - 0.99), at presentation. The best cortisol post-DST threshold to predict ACS development in NFAI patients was 1.4 µg/dl (AUC 0.67, 95% CI 0.62 - 0.72, sensitivity 58% and specificity 72%). Significant tumor growth was observed in 23 out of 401 patients (5.6%). Median tumor growth in these patients was 11.0 ± 4.9 mm. Unilateral laparoscopic adrenalectomy was performed in 2 patients, and histology was benign in both. Tumour growth was more common in women (HR 3.7, 95% CI 1.4 - 9.3), but other predictive variables were not identified. Final tumor size was linearly correlated with initial (r = 0.12, P = 0.012) and last-visit cortisol post-DST (r = 0.14, P = 0.018). ACS was developed during follow-up in 18.8% of tumours that demonstrated significant growth; and in 8.7% of tumors that remained stable in size (P = 0.181).

Conclusions

11% of patients with NFAIs developed ACS; and 5.6% of tumors grew during follow-up. Cortisol post-DST levels at presentation are associated with the risk of ACS development and are linearly associated with the follow-up adrenal tumor size.