Objective: To investigate the androstenedione, 17a-hydroxyprogesterone (17-OHP), and dehydroepiandrosterone sulfate (DHEAS) basal levels and responses to adrenocorticotropic hormone (ACTH) in patients with adrenal incidentalomas in order to determine which enzyme defects are present.
Methods: In a study group of 23 patients (18 women and 5 men who ranged in age from 16 to 70 years) with incidentally discovered asymptomatic adrenal masses, ACTH stimulation was performed to evaluate the secretory responses of 17-OHP and DHEAS. The same test was performed in 15 age- and sex-matched control subjects.
Results: Of the 23 patients, 16 (70%) had a 17-OHP peak >30 nmol/L. The 17-OHP response to ACTH stimulation was significantly higher in patients with adrenal incidentalomas than in control subjects (P<0.001). Fourteen patients had basal DHEAS levels below the 3rd percentile of the control group (1.4 +/- 0.1 mmol/L). The mean stimulated DHEAS level was 1.7 +/- 0.2 mmol/L (range, 0.8 to 4.1) in patients with incidentalomas and 4.2 +/- 0.4 mmol/L (range, 1.8 to 5.6) in the control group (P<0.001). In 13 patients, stimulated DHEAS levels were low in association with high 17-OHP levels. Basal ACTH levels did not differ significantly between patients (8.14 +/- 1.2 pmol/L) and control subjects (8.73 +/- 0.7 pmol/L). Basal androstenedione levels were significantly lower in patients (1.9 +/- 0.3 nmol/L) than in control subjects (5.7 +/- 2.5 nmol/L) (P<0.001). No significant correlation was found between 17-OHP levels and tumor size.
Conclusion: Enzyme defects may have an important role in adrenal incidentalomas. Two possible explanations for the observed abnormalities of steroid metabolism in patients with incidentalomas are that (1) the incidentalomas are true primary tumors that have aberrant steroid metabolic pathways or (2) such patients have underlying congenital adrenal hyperplasia that leads, over time, to development of pseudotumors. To assess these two possibilities, we need further studies such as genetic investigations, postoperative test results, and evidence relating the size of the adrenal mass to steroid-suppressible treatment.