Preclinical Cushing's syndrome in adrenal incidentalomas

Adrenal tumors are usually diagnosed by clinical symptoms of
hormone excess. The increasing use of ultrasound and computed
tomography results in the detection of a substantial number of
incidentally discovered adrenal tumors. Most of these tumors are
nonfunctional adrenocortical adenomas, but a few cases of
subclinical cortisol production in "incidentalomas" have been
reported. We investigated prospectively the prevalence of
autonomous cortisol production in 68 patients (44 females and 24
males, aged 25-90 yr) with adrenal incidentalomas at our
institution. As a screening procedure all patients with
incidentalomas underwent an overnight dexamethasone suppression
test (1 mg). Patients who failed to suppress serum cortisol below
140 nmol/L (5 micrograms/dL) underwent more comprehensive studies
(prolonged dexamethasone suppression test, determination of the
diurnal rhythm of cortisol secretion in saliva, and CRH stimulation
test). Eight patients (12% of all patients with incidentalomas; 5
females and 3 males, aged 25-71 yr) were finally identified as
having cortisol- producing tumors, and the findings in these
patients were compared with those of overt Cushing's syndrome in 8
patients (8 females, aged 26-50 yr) suffering from
cortisol-producing adrenal adenomas. The tumor size of patients
with cortisol-producing incidentalomas ranged from 2-5 cm. No
specific signs and symptoms of hypercortisolism were present, but
arterial hypertension (seven of eight subjects), diffuse obesity
(four of eight subjects), and noninsulin-dependent diabetes
mellitus (NIDDM; two of eight subjects) were frequently observed.
Baseline cortisol levels were in the normal to upper normal range,
whereas baseline ACTH levels were suppressed in five of the eight
patients. In none of the patients was serum cortisol suppressible
by low dose or high dose dexamethasone. The ACTH and cortisol
responses to CRH were normal in two, blunted in one, and suppressed
in four patients. Unilateral adrenalectomy was performed in seven
patients and resulted in temporary adrenal insufficiency in four of
them. After surgery, improvement of arterial hypertension, a
permanent weight loss in obese subjects, and a better metabolic
control of NIDDM were noted in the majority of patients. The
following conclusions were reached. Incidentally diagnosed adrenal
tumors with pathological cortisol secretion in otherwise clinically
asymptomatic patients are more frequently observed than previously
assumed. Adrenocortical insufficiency is a major risk in these
patients after adrenalectomy. After surgery, hypertension, obesity,
and NIDDM may improve. Patients with asymptomatic adrenal
incidentalomas, therefore, should be screened for cortisol
production by means of an overnight dexamethasone suppression test.