Abstract
Purpose: To assess the risk of developing autonomous cortisol secretion (ACS) and tumour growth in non-functioning adrenal incidentalomas (NFAIs). Methods: Multicentre retrospective observational study of patients with NFAIs. ACS was defined as serum cortisol >1.8 µg/dL after 1 mg-dexamethasone suppression test (DST) without specific data on Cushing’s syndrome. Tumour growth was defined as an increase in maximum tumour diameter >20% from baseline; and of at least 5 mm. Results: Of 654 subjects with NFAIs included in the study, both tumour diameter and DST were re-evaluated during a follow-up longer than 12 months in 305 patients. After a median follow-up of 41.3 (IQR 24.7–63.1) months, 10.5% of NFAIs developed ACS. The risk for developing ACS was higher in patients with higher serum cortisol post-DST levels (HR 6.45 for each µg/dL, p = 0.001) at diagnosis. Significant tumour growth was observed in 5.2% of cases. The risk of tumour growth was higher in females (HR 10.7, p = 0.004). Conclusions: The frequency of re-evaluation with DST in NFAIs during the initial 5 years from diagnosis can probably be tailored to the serum cortisol post-DST level at presentation. Re-evaluation of NFAIs with imaging studies, on the other hand, seems unnecessary in most cases, particularly if the initial imaging demonstrates features specific to typical adenoma, given the low rate of significant tumour growth.
Highlights
The increasing use of imaging studies has led to increasing diagnosis of adrenal incidentalomas (AIs) in recent years
We excluded patients with: (i) known diagnosis of hereditary syndromes associated with adrenal tumours; (ii) chronic treatment with glucocorticoids or drugs that impair dexamethasone metabolism; (iii) current treatment with oral hormonal contraceptives; and (iv) AIs identified during the extension study of an extra-adrenal primary cancer
24.4% (43/176) of non-functioning adrenal incidentalomas (NFAIs) had ACTH below 10 pg/mL. 24 h-UFC was within reference ranges in all patients
Summary
The increasing use of imaging studies has led to increasing diagnosis of adrenal incidentalomas (AIs) in recent years. In patients with AIs there are two important aspects that need to be ruled out at presentation: (1) malignancy, which is generally done by imaging characteristics; and (2) functionality [2]. Autonomous cortisol secretion (ACS) is the most common functional alteration in AIs and it has been associated with an increased cardiometabolic risk [3]. Despite the known risk for ACS development and its associated increased cardiometabolic risk [5,6], it remains controversial whether NFAIs require long-term followup; or how closely they should be monitored. The European Society of Endocrinology and the European network for the study of adrenal tumours (ESE/ENSAT) [2] and the Italian Association of Clinical Endocrinologists (EMA) [7] guidelines consider it unnecessary to repeat hormonal or imaging evaluations in NFAIs if radiological features are typical of adenoma at presentation. Under the same circumstances, the National Institutes of Health (NIH) [8], the French Endocrinology Society (FES) [9], the Spanish Society of Endocrinology and Nutrition (SEEN) [10] and the American Association of Clinical Endocrinologists (AACE/AASE) [11] guidelines recommend repeating a dexamethasone suppression test annually for up to 5 years and imaging studies for at least one year in tumours less than 4 cm or two years if they are 4 cm or larger
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