In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing's syndrome. The workshop was organized by the University of Ancona and sponsored by the Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing's syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.

Objective: To assess currently available evidence on adrenal incidentaloma and provide recommendations for clinical practice. Design: A panel of experts (appointed by the Italian Association of Clinical Endocrinologists (AME)) appraised the methodological quality of the relevant studies, summarized their results, and discussed the evidence reports to find consensus. Radiological assessment: Unenhanced computed tomography (CT) is recommended as the initial test with the use of an attenuation value of %10 Hounsfield units (HU) to differentiate between adenomas and non-adenomas. For tumors with a higher baseline attenuation value, we suggest considering delayed contrast-enhanced CT studies. Positron emission tomography (PET) or PET/CT should be considered when CT is inconclusive, whereas fine needle aspiration biopsy may be used only in selected cases suspicious of metastases (after biochemical exclusion of pheochromocytoma). Hormonal assessment: Pheochromocytoma and excessive overt cortisol should be ruled out in all patients, whereas primary aldosteronism has to be considered in hypertensive and/or hypokalemic patients. The 1 mg overnight dexamethasone suppression test is the test recommended for screening of subclinical Cushing's syndrome (SCS) with a threshold at 138 nmol/l for considering this condition. A value of 50 nmol/l virtually excludes SCS with an area of uncertainty between 50 and 138 nmol/l. Management: Surgery is recommended for masses with suspicious radiological aspects and masses causing overt catecholamine or steroid excess. Data are insufficient to make firm recommendations for or against surgery in patients with SCS. However, adrenalectomy may be considered when an adequate medical therapy does not reach the treatment goals of associated diseases potentially linked to hypercortisolism.

The frequency of the hereditary forms of pheochromocytoma/paraganglioma varies depending on the family history and the clinical presentation. A positive family history and an accurate clinical evaluation of patients are strong indicators of which genes should be screened first.

The aim of this study was to perform a national survey on occasionally discovered adrenal masses [adrenal incidentalomas (AI)] under the auspices of the Italian Society of Endocrinology. This multicentric and retrospective evaluation of patients with AI includes 1096 cases collected in 26 centers between 1980 and 1995. Relevant information was obtained by means of a specifically tailored questionnaire. Of the 1096 forms received, 1004 were retained for final analysis. Patients were 420 males and 584 females, aged between 15-86 yr (median, 58 yr). Mass size (computed tomography measurement) ranged from 0.5-25 cm (median, 3.0 cm). Hormonal work-up demonstrated that 85% of the masses were nonhypersecretory, 9.2% were defined as subclinical Cushing's syndrome, 4.2% were pheochromocytomas, and 1.6% were aldosteronomas. Adrenalectomy was performed in 380 patients with removal of 198 cortical adenomas (52%), 47 cortical carcinomas (12%), 42 pheochromocytomas (11%), and other less frequent tumor types. Patients with carcinoma were significantly younger than patients with adenoma (median, 46; range, 17-84; vs. 57, 16-83 yr; P = 0.05). Adenomas were significantly smaller than carcinomas (3.5, 1-15 vs. 7.5, 2.6-25 cm; P < 0.001), and a cut-off at 4.0 cm had the highest sensitivity (93%) in differentiating between benign and malignant tumors. Hormonal work-up of patients with subclinical Cushing's syndrome showed low baseline ACTH in 79%, cortisol unsuppressibility after 1 mg dexamethasone in 73%, above normal urinary free cortisol in 75%, disturbed cortisol rhythm in 43%, and blunted ACTH response to CRH in 55%. Only 43% of patients with pheochromocytoma were hypertensive, and 86% showed elevated urinary catecholamines. All patients with aldosteronoma were hypertensive and had suppressed upright PRA. These results indicate that mass size is the most reliable variable in separating benign from malignant AI. Adrenalectomy should be recommended for AI greater than 4.0 cm because of the increased risk of malignancy, especially in young patients. Endocrine evaluation should be performed in all patients to identify silent states of hormone excess.

Patients with active CS present a remarkably increased cardiovascular risk. Considering that the biochemical cure of hypercortisolism is often difficult to obtain, especially in Cushing's disease, and that cardiovascular risk could persist even after the 'cure', control of risk factors should be one of the primary goals of the therapy.