Endocrine Abstracts

Background: Hormonal studies have detected subtle abnormalities of the hypothalamic–pituitary–adrenal (HPA) axis due to autonomous cortisol secretion, in a percentage of patients with adrenal incidentalomas, a condition termed as subclinical Cushing’s syndrome. The diagnostic criteria and the clinical significance of this condition are still controversial and consequently there is uncertainty for its management. Data defining the natural course of these tumors, will help to determine clinical implications and appropriate management, but are still inadequate.

Objective: Prospective long-term follow-up study of patients with apparently benign adrenal incidentalomas and without overt hyperfunction at initial diagnosis, in order to assess their hormonal activity and their long-term growth pattern.

Patients-methods: From a group of 89 patients with adrenal incidentalomas, 34 patients with a mass diameter 1.0–6.0 cm (2.2±0.8, median 2.0) were followed-up for 12–144 months, (62.1±33.5, median 57.0), with a hormonal (plasma cortisol rhythm, morning plasma ACTH, serum DHEA-S, serum aldosterone and plasma renine activity, low dose dexamethasone suppression test, 24 h urinary VMA and metanephrines and 24 h urinary free cortisol) and morphological evaluation (CT scan) every 12–24 months. The diagnosis of subclinical Cushing’s syndrome was based on a post-LDDST plasma cortisol level >1.8 μg/dl combined with an abnormal result of at least one other test of the HPA axis and the absence of clinical signs of cortisol excess.

Results: At diagnosis 23 patients had a normal adrenal function and 11 had subclinical Cushing’s syndrome. During follow-up adrenal function remained normal in 22 patients, subclinical Cushing’s syndrome was reassessed in five patients, whilst intermittent subclinical autonomous cortisol hypersecretion was found in seven patients. None of the patients developed Cushing’s syndrome. A change in mass size (≥0.5 cm) was found in 12 patients (an increase in nine patients, with no signs of malignancy and a reduction in 3).

Conclusion: These data show that subclinical autonomous cortisol hypersecretion may be intermittent in a significant percentage of patients. This finding supports a wide range of variability from non-functioning adrenal adenoma to autonomous cortisol secreting adrenal adenoma. The spectrum of intensity of subclinical autonomous cortisol secretion may explain the contrasting results of studies examining long-term adverse implications this disorder. These data also show that a growth tendency is observed in some adrenal incidentalomas, without evidence of malignant transformation.