INCREASED 17A-HYDROXYPROGESTERONE RESPONSE TO ACTH IN SILENT ADRENAL ADENOMA - CAUSE OR EFFECT

OBJECTIVE Recent studies suggest a possible connection between silent adrenal nodules and mild forms of 21-hydroxylase deficiency. It remain s unclear whether the enzymatic deficiency is generalized or intrinsic to the adrenal mass. To help to clarify this, we have studied 17 alph a-OH-progesterone (17OH-P) response to ACTH stimulation in a group of patients with adrenal 'incidentaloma' in comparison with normal subjec ts. In patients who underwent surgical treatment, the test was repeate d to evaluate possible modifications in 17OH-P behaviour after resecti on of the adrenal mass. SUBJECTS AND METHODS Fifteen subjects with inc identally discovered asymptomatic adrenal masses were studied. Basal h ormone evaluations were normal, with normal cortisol suppression after low-dose dexamethasone. Iodocholesterol scanning, performed In 12 pat ients, showed normal bilateral adrenal uptake in 2 subjects and an inc reased uptake on the side of the lesion in 10 subjects. In every patie nt, ACTH stimulation was performed to evaluate the secretory response of cortisol, 17OH-P, progesterone and dehydroepiandrosterone sulphate. An Identical test was performed in 10 control subjects with normal ad renal glands, matched for age and sex. In six patients with an adrenal lesion >3.5 cm, the ACTH stimulation test was repeated one month afte r surgery. RESULTS The 17OH-P response to ACTH stimulation was signifi cantly higher in subjects with adrenal 'incidentaloma' than in control s (P < 0.01). In particular, 10 subjects out of 15 (66%) evidenced a 1 7OH-P peak >18 nmol/l at 60 minutes. No differences were seen in basel ine 17OH-P or cortisol levels or in cortisol response to ACTH between the two groups. Dehydroepiandrosterone sulphate concentrations were si gnificantly lower in patients with adrenal 'incidentaloma' than in nor mals. In six patients who had an increased 17OH-P response to ACTH on initial evaluation, the ACTH test was repeated one month after surgery . In five of these patients, 17OH-P response to ACTH was clearly reduc ed, suggesting that in these cases the enzymatic defect was restricted to the adenoma. In the other patient, however, stimulated 17OHP level s remained unchanged. In this case, therefore, all of the adrenal tiss ue seems to be involved, suggesting a late-onset 21-hydroxylase defici ency. No significant modifications in cortisol response to ACTH were o bserved. CONCLUSION It seems therefore that in some cases of incidenta loma the steroidogenic enzymatic defect may be secondary to the adenom atous proliferation, while in others such defects may induce the devel opment of silent adrenal nodules.