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


METHODS
A prospective study of 52 patients admitted to a single hospital.


METHODS
Fifty-two consecutive subjects (mean age 56.0 years, range 24-81 years) with an incidentally discovered adrenal tumour were studied.


METHODS
The 21-hydroxylase reserve was assessed by intravenous bolus administration of 1-24 ACTH (tetracosactrin) with measurement of basal and stimulated serum 17 alpha-hydroxyprogesterone (17-OHP) concentrations. Impaired 21-hydroxylase activity was defined as an exaggerated 17-OHP response, with a 17-OHP increment exceeding 7.9 nmol/l. 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 7.9 nmol/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 glucocorticoid 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-hydroxylase defiency is a common finding in patients with an adrenal incidentaloma, even in the absence of a congenital adrenal hyperplasia 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-hydroxylase activity in the tumour, which retains ACTH responsiveness.
Seppel
T
T
Department of Endocrinology and Rheumatology, Heinrich Heine University Düsseldorf, Germany.
Schlaghecke
R
R
D019326:17-alpha-Hydroxyprogesterone; D000236:Adenoma / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D000312:Adrenal Hyperplasia, Congenital; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013255:Steroid 21-Hydroxylase / Q000097:blood
D006908:Hydroxyprogesterones; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase