Augmented 17α‐hydroxyprogesterone response to ACTH stimulation as evidence of decreased 21‐hydroxylase activity in patients with incidentally discovered adrenal tumours ('incidentalomas')

Summary OBJECTIVE Recent studies have indicated that the syndrome of congenital adrenal hyperplasia due to 21‐hydroxylase deficiency is closely associated with the development of benign adrenocortical tumours. Tumour formation is thought to be a consequence of ACTH hypersecretion which results from the lack of glucocorticoid synthesis. The aim of this study was to evaluate 21‐hydroxylase activity in patients with an incidentally discovered adrenal mass ('Incidentaloma') without a history of congenital adrenal hyperplasia. DESIGN A prospective study of 52 patients admitted to a single hospital. PATIENTS Fifty‐two consecutive subjects (mean age 56·0 years, range 24–81 years) with an incidentally discovered adrenal tumour were studied. MEASUREMENTS The 21‐hydroxylase reserve was assessed by intravenous bolus administration of 1‐24 ACTH (tetracosactrin) with measurement of basal and stimulated serum 17α‐hydroxyprogesterone (17‐OHP) concentrations. Impaired 21‐hydroxylase activity was defined as an exaggerated 17‐OHP response, with a 17‐OHP increment exceeding 7‐9nmolll. Basal and stimulated cortisol concentrations, and basal ACTH were also measured. RESULTS Baseline levels of 17‐OHP were normal in 44 and elevated in 8 subjects. In 37 patients (71·2%), the 17‐OHP increment following ACTH administration exceeded 7·9nmol/l, demonstrating mildly decreased 21‐hydroxylase activity. In these subjects, the peak serum 17‐OHP correlated with the tumour diameter. In the patients with apparently normal 21‐hydroxylase activity, no significant correlation was found between 17‐OHP concentrations and tumour size. All patients had a stimulated serum cortisol above 550 nmol/l reflecting intact adrenal gluco‐corticoid reserve. There were no other differences between the group with exaggerated and the group with normal 17‐OHP Increment. The tumours were removed from two women with augmented 17‐OHP responses and this was followed by normalization of 17‐OHP dynamics. CONCLUSIONS Biochemical evidence for partial 21‐hydroxyiase defiency is a common finding in patients with an adrenal Incidentaloma, even in the absence of a congential adrenal hyperpiasia history. Exaggerated 17‐OHP increment is not accompanied by decreased adrenal glucocorticoid reserve. Normalization of the 17‐OHP response after surgical treatment suggests that the phenomenon results from reduced 21‐hydroxyiase activity in the tumour, which retains ACTH responsiveness.