CLINICAL STUDY Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas R Giordano 1 , E Marinazzo 2 , R Berardelli 2 , A Picu 2 , M Maccario 2 , E Ghigo 2 and E Arvat 2 1 Department of Clinical and Biological Sciences and 2 Division of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine, University of Turin, Azienda Ospedaliero-Universitaria San Giovanni Battista, Corso Dogliotti 14, 10126 Turin, Italy (Correspondence should be addressed to E Arvat; Email: emanuela.arvat@unito.it) Abstract Objective: To evaluate long-term morphological, functional, and clinical outcome in adrenal incidentalomas. Design and methods: A total of 118 patients (77 F and 47 M; age 62.3G1.0 years) with adrenal incidentalomas were evaluated at baseline and followed-up for median 3 years (range 1–10 years) by clinical, biochemical, hormonal, and morphological evaluation. Among them, six patients with diagnosis of subclinical Cushing’s syndrome (SCS) underwent surgery. Results: At entry, 86% (nZ102) of tumors were nonfunctioning (NF) and 14% (nZ16) showed SCS. Comparing NF with SCS patients, a significantly higher percentage of dyslipidemia was found in the group of SCS patients (50 vs 23%, PZ0.033). During follow-up, adrenal function remained normal in all NF patients, none of them developed subclinical or overt endocrine disease. The cumulative risk of mass enlargement was globally low (25%), but progressive up to 8 years. SCS was confirmed in all patients, and none of them shifted to overt Cushing’s syndrome. The cumulative risk of developing metabolic–cardiovascular abnormalities was globally low (22%), but progressive up to 8 years and new diseases were recorded in the group of NF patients only (three patients with dyslipidemia, four with impaired fasting glucose/impaired glucose tolerance, and three with diabetes mellitus). SCS patients who underwent surgery did not show any significant clinical improvement. Conclusions: The risk of mass enlargement, hormonal, and metabolic impairment over time is globally low. Conservative management seems to be appropriate, but further prospective studies are needed to establish the long-term outcome of such patients, especially for metabolic status, cardiovascular risk profile and their relationship with endocrine function. European Journal of Endocrinology 162 779–785 Introduction Adrenal incidentalomas, clinically unapparent adrenal masses discovered by abdominal imaging procedures for unrelated reasons, have become a common finding in clinical practice. In fact, the widespread use of abdominal ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) have led to an increase in the detection of adrenal incidentalomas in recent years, ranging between 1 and 6% in different series (1–4). Although the majority of adrenal lesions are benign non-hypersecreting cortical adenomas, they represent a clinical concern because of the risk not only of malignancy but also of subclinical hormonal hypersecretion, mainly cortisol secretion (5, 6). The latter condition, the so called subclinical Cushing’s syndrome (SCS), is characterized by subtle alterations of the hypothalamus–pituitary–adrenal (HPA) axis due to autonomous cortisol-secreting adenomas without signs or symptoms of overt hypercortisolism (6). Data concerning the prevalence of SCS in patients with adrenal incidentalomas are controversial, due to different diagnostic criteria used, as no defined con- sensus for the biochemical diagnosis is available (6–9). The initial evaluation of a patient with an adrenal incidentaloma aims at defining the functional status and the possibility of malignant disease (3, 5, 10, 11). Except for masses suspected for malignancy and/or clearly hyperfunctioning, the majority of authors recommend a conservative approach (5, 10–20). However, no com- prehensive guidelines exist concerning the frequency and duration of follow-up of patients with adrenal incidentalomas, due to limited data on the natural history and, namely, on possible changes in adrenal size and/or hormonal pattern. Moreover, although subclinical glucocorticoid excess of SCS patients has been supposed to induce metabolic derangement, it is controversial whether this pathological condition is or is not associated with long-term morbidity, may progress to overt Cushing’s syndrome (CS), and whether treatment to reverse subtle glucocorticoid excess can influence the outcome of the disease (21, 22). European Journal of Endocrinology (2010) 162 779–785 ISSN 0804-4643 q 2010 European Society of Endocrinology DOI: 10.1530/EJE-09-0957 Online version via www.eje-online.org