SUBCLINICAL CUSHINGS-SYNDROME IN ADRENAL INCIDENTALOMA

OBJECTIVE Some patients with incidentally discovered adrenal adenomas display autonomous cortisol secretion not fully restrained by pituitar y feedback, a condition that may be defined as subclinical Cushing's s yndrome. We have evaluated the presence of subclinical Gushing's syndr ome and its natural history in a cohort of patients with incidentally discovered adrenal adenomas. PATIENTS Fifty-three consecutive patients (30 women and 23 men; median age 58 years, range 18-81 years) were st udied. Diagnostic procedures were initiated for extra-adrenal complain ts. Patients with known extra-adrenal malignancies or patients with hy pertension of possible endocrine origin were excluded. MEASUREMENTS Al l patients underwent the following endocrine evaluation: (1) measureme nt of DHEA-S at 0800 h, (2) measurement of serum cortisol at 0800 and 2400 h, (3) measurement of the 24-h excretion of urinary free cortisol (UFG), (4) overnight low-dose dexamethasone suppression test, (5) mea surement of plasma ACTH at 0800 h (mean of at least two samples on dif ferent days), (6) oCRH stimulation test. Different groups of healthy s ubjects recruited from the hospital medical staff and their relatives served as controls for the various tests. The same endocrine work-up w as repeated after 12 months in 25 patients. All patients were followed up at regular intervals for at least 12 months with clinical examinat ion and abdominal computed tomography. Subclinical hypercortisolism wa s arbitrarily defined as definitive, probable or possible, according t o the degree of endocrine abnormalities. RESULTS UFC was significantly higher in patients with incidentaloma than in controls (262, 25-690 n mol/24 h versus 165, 25-772 nmol/24 h; P = 0.012). The percentage of s ubjects who did not suppress on dexamethasone was greater among patien ts than among healthy subjects (9/53 (17%) versus 5/103 (5%), P = 0.02 6). Plasma ACTH concentrations were lower in patients with adrenal inc identaloma than in controls (3, 1-9 pmol/l versus 5, 1-14 pmol/l; P = 0.014). These findings consistently point toward a functional autonomy of the adrenal adenomas even if the degree of cortisol excess is mild . Three patients fulfilled the criteria for definitive subclinical hyp ercortisolism, five for probable and two possible, but none of them ex perienced clinical and/or biochemical progression to overt hypercortis olism after 12 months. During follow-up, no signs of extra-adrenal mal ignancy became manifest and the size of the mass did not increase sign ificantly in any patient. CONCLUSIONS This study provides a clear demo nstration of the current opinion that some patients with incidentally discovered adrenal adenomas may be exposed to a subtle, silent hyperco rtisolism. In some patients, in whom the clustering of more abnormalit ies in the hypothalamo-pituitary-adrenal axis occurs, subclinical Gush ing's syndrome could be assumed. This term should be preferred to that of pre-clinical Gushing's syndrome since the biochemical abnormalitie s do not become clinically manifest, at least in the short term.