AUGMENTED 17-ALPHA-HYDROXYPROGESTERONE RESPONSE TO ACTH STIMULATION AS EVIDENCE OF DECREASED 21-HYDROXYLASE ACTIVITY IN PATIENTS WITH INCIDENTALLY DISCOVERED ADRENAL-TUMORS (INCIDENTALOMAS)

OBJECTIVE Recent studies have indicated that the syndrome of congenita l adrenal hyperplasia due to 21-hydroxylase deficiency is closely asso ciated with the development of benign adrenocortical tumours. Tumour f ormation is thought to be a consequence of ACTH hypersecretion which r esults from the lack of glucocorticoid synthesis. The aim of this stud y was to evaluate 21-hydroxylase activity in patients with an incident ally discovered adrenal mass ('incidentaloma') without a history of co ngenital adrenal hyperplasia. DESIGN A prospective study of 52 patient s admitted to a single hospital. PATIENTS Fifty-two consecutive subjec ts (mean age 56.0 years, range 24-81 years) with an incidentally disco vered adrenal tumour were studied. MEASUREMENTS The 21-hydroxylase res erve was assessed by intravenous bolus administration of 1-24 ACTH (te tracosactrin) with measurement of basal and stimulated serum 17 alpha- hydroxyprogesterone (17-OHP) concentrations. Impaired 21-hydroxylase a ctivity was defined as an exaggerated 17-OHP response, with a 17-OHP i ncrement exceeding 7.9 nmol/l. Basal and stimulated cortisol concentra tions, and basal ACTH were also measured. RESULTS Baseline levels of 1 7-OHP were normal in 44 and elevated in 8 subjects. In 37 patients (71 .2%), the 17-OHP increment following ACTH administration exceeded 7.9 nmol/l, demonstrating mildly decreased 21-hydroxylase activity. In the se subjects, the peak serum 17-OHP correlated with the tumour diameter . In the patients with apparently normal 21-hydroxylase activity, no s ignificant correlation was found between 17-OHP concentrations and tum our size. All patients had a stimulated serum cortisol above 550 nmol/ l reflecting intact adrenal glucocorticoid reserve. There were no othe r differences between the group with exaggerated and the group with no rmal 17-OHP increment. The tumours were removed from two women with au gmented 17-OHP responses and this was followed by normalization of 17- OHP dynamics. CONCLUSIONS Biochemical evidence for partial 21-hydroxyl ase defiency is a common finding in patients with an adrenal incidenta loma, even in the absence of a congential adrenal hyperplasia history. Exaggerated 17-OHP increment is not accompanied by decreased adrenal glucocorticoid reserve. Normalization of the 17-OHP response after sur gical treatment suggests that the phenomenon results from reduced 21-h ydroxylase activity in the tumour, which retains ACTH responsiveness.