Incidentally discovered adrenal masses are mostly benign, asymptomatic lesions, often arbitrarily considered as nonfunctioning
tumors. Recent studies, however, have reported increasing evidence that subtle
cortisol production and abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are more frequent than previously thought. The purpose of this study was to investigate the clinical and hormonal features of patients with incidentally discovered adrenal
adenomas, in relation to their clinical outcome. Fifty consecutive patients with incidentally detected adrenal
adenomas, selected from a total of 65 cases of
adrenal incidentalomas, were prospectively evaluated. All of them underwent abdominal computed tomography scan and hormonal assays of the HPA axis function: circadian rhythm of plasma
cortisol and
ACTH, urinary
cortisol excretion,
17-hydroxyprogesterone,
androgens,
corticotropin stimulation test and low-dose (2 mg)
dexamethasone test. The patients were reevaluated at regular intervals (6, 12, and 24 months) for a median period of 38 months. Subtle
hypercortisolism, defined as abnormal response to at least 2 standard tests of the HPA axis function in the absence of clinical signs of
Cushing's syndrome (CS), was defined as subclinical CS. Mild-to-severe
hypertension was found in 24 of 50 (48%) patients, type-2 diabetes in 12 of 50 (24%), and
glucose intolerance in 6 of 50 (12%) patients. Moreover, 18 of 50 patients (36%) were diffusely obese (body mass index, determined as weight/height2, > 25), and 14 patients (28%) had serum
lipid concentration abnormalities (
cholesterol > or = 6.21 mmol/L,
low-density lipoprotein cholesterol > or = 4.14 mmol/L and/or
triglycerides > or = 1.8 mmol/L). Compared with a healthy population, bone mineral density Z-score, determined by the DEXA technique, tended to be slightly (but not significantly) lower in patients with adrenal
adenoma (-0.41 SD). Endocrine data were compared with 107 sex- and age-matched controls, and patients with
adenomas were found to have heterogeneous hormonal abnormalities. In particular, significantly higher serum
cortisol values (P < 0.001), lower
ACTH concentration (P < 0.05), and impaired
cortisol suppression by
dexamethasone (P < 0.001) were observed. Moreover, in patients with
adenomas,
cortisol, 17-OH
progesterone, and
androstenedione responses to
corticotropin were significantly increased (P < 0.001, all), whereas
dehydroepiandrosterone sulfate levels were significantly lower at baseline, with blunted response to
corticotropin (P < 0.001, both). However, the criteria for subclinical CS were met by 12 of 50 (24%) patients. Of these, 6 (50%) were diffusely obese, 11 (91.6%) had mild-to-severe
hypertension, 5 (41.6%) had type-2
diabetes mellitus, and 6 (50%) had abnormal serum
lipids. The clinical and hormonal features improved in all patients treated by
adrenalectomy, but seemed unchanged in all those who did not undergo surgery (follow-up, 9 to 73 months), except for one, who was previously found as having nonfunctioning
adenoma and then revealed to have subclinical CS. In conclusion, an unexpectedly high prevalence of subtle autonomous
cortisol secretion, associated with high occurrence of
hypertension,
diabetes mellitus, elevated
lipids, and diffuse
obesity, was found in incidentally discovered adrenal
adenomas. Although the pathological entity of a subclinical
hypercortisolism state remained mostly stable in time during follow-up,
hypertension, metabolic disorders, and hormonal abnormalities improved in all patients treated by
adrenalectomy. These findings support the hypothesis that clinically silent
hypercortisolism is probably not completely asymptomatic.