Objective: Increasing evidence favours subtle glucocorticoid excess in many patients with adrenal incidentalomas. However, existing evidence is based mainly on the overnight dexamethasone suppression test, a test that is commonly abnormal even among clinically euadrenal subjects. The aim of the present study was to evaluate patients with adrenal incidentalomas for subtle glucocorticoid excess by the more specific low-dose dexamethasone test (LDDST). Moreover, since the criteria of what constitutes an abnormal cortisol response following this test have been largely anecdotal, we report our results in comparison with those obtained in clinically euadrenal subjects, and patients with Cushing's syndrome.
Design: A prospective study of 57 patients with adrenal incidentalomas with CT characteristics highly suggestive of benign adrenocortical adenomas and 85 clinically euadrenal subjects consisting of 54 obese women with BMI > 30 kg/m2 (range 30-54.7), 13 women with BMI < 30 kg/m2 (range 20.3-29.6) and 18 healthy volunteers (10 women and eight men) over 40 years of age (mean age 51.7 +/- 9.9, range 40-74; mean BMI 30 +/- 6.6, range 20.3-47.5 kg/m2). A retrospective analysis was performed on 60 patients with a confirmed diagnosis of Cushing's syndrome.
Measurements: All subjects were admitted to the endocrine ward and underwent a standard LDDST, as follows: after a 48-h stabilization period, a 24-h urine collection for basal urinary free cortisol was performed. Basal serum cortisol and plasma ACTH were measured at 0800 h the following day, and subjects were started on dexamethasone 0.5 mg 6-hourly for 2 days. Post-dexamethasone cortisol and ACTH levels were measured at 0800 h, 6 h after the last dose of dexamethasone.
Results: Following dexamethasone suppression serum cortisol concentrations became undetectable (< 28 nmol/l) in all clinically euadrenal subjects. In patients with incidentally discovered adrenal masses, post-LDDST cortisol concentrations were undetectable in 12 (21%), between 28-140 nmol/l in 38 (67%), and 140-216 nmol/l in seven (12%) patients; post-LDDST cortisol values correlated positively with the size of the adenoma (r = +0.482, P < 0.001). Post-LDDST cortisol concentrations in patients with Cushing's syndrome ranged from 85 to 1786 nmol/l; in 3/42 (7%) patients with ACTH-dependent Cushing's syndrome cortisol concentrations were < 140 nmol/l.
Conclusions: On the basis of our data in a large group of clinically euadrenal subjects, we suggest that following LDDST cortisol concentrations should become undetectable with the currently used radioimmunoassays. In patients with adrenal incidentalomas, application of the LDDST confirmed the presence of incomplete suppression of cortisol in the majority of patients. We suggest that the LDDST is a sensitive index of autonomous cortisol production in patients with adrenal incidentalomas; following this test a grading of subtle glucocorticoid excess may be obtained but future studies correlating biochemical, clinical and epidemiological data are required, in order to develop widely agreed cut-off levels of clinically significant glucocorticoid excess in these patients.