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Clinically inapparent adrenal masses, or adrenal incidentalomas, are discovered inadvertently in the course of work-up or treatment of unrelated disorders. Cortical adenoma is the most frequent tumour detected incidentally, but adrenocortical cancer, phaeochromocytoma and metastasis are not rare. Two critical questions should be answered before trying to outline the management of adrenal incidentaloma: (1) which tumours may cause harm to the patient, and (2) can we recognize and effectively treat such tumours? Based on the available scientific evidence, two major recommendations should be made: (1) identify either primary (adrenocortical cancer) or secondary (adrenal metastasis) malignancy; (2) identify phaeochromocytoma. Radiological evaluation is the key to the differential diagnosis of benign and malignant tumours. Endocrine testing is necessary to exclude phaeochromocytoma in all patients with an adrenal incidentaloma because this tumour may remain undiagnosed after imaging studies. The management of clinically inapparent adrenal adenomas may vary depending whether or not they are functioning. It is reasonable to screen for primary aldosteronism all hypertensive patients and recommend adrenalectomy when an aldosterone-producing adenoma is confirmed. A subset of adenomas secretes cortisol autonomously and may lead to mild hypercortisolism, a condition defined as subclinical Cushing''s syndrome. The criteria for defining subclinical Cushing''s syndrome are controversial, and we currently do not have sufficient evidence to define a gold standard for screening. Also the management of this condition is largely empirical, and data are insufficient to indicate the superiority of a surgical or non-surgical approach to managing patients with subclinical Cushing''s syndrome. [Copyright &y& Elsevier]

Adrenocortical carcinoma (ACC) is an aggressive cancer characterized by poor survival. Apart from radical surgery, there is a limited range of therapeutic options and mitotane remains the cornerstone of medical treatment of ACC in either adjuvant or palliative settings. The aim of adjuvant mitotane therapy is to reduce the risk of ACC recurrence following surgical removal of the tumor. Use of mitotane in an adjuvant setting is off-label, but the recent guidelines endorsed by the European Society of Endocrinology (ESE) and the European Network for the Study of Adrenal Tumors (ENSAT) recommend it in ACC patients at high risk of recurrence. The palliative use of mitotane for treatment of advanced ACC aims at controlling tumor progression and, when present, hormone secretion. In this clinical setting, mitotane is used in association with chemotherapy to treat the more aggressive forms, while mitotane monotherapy is reserved for less progressive ACC. Many years after its introduction in clinical practice, there are still uncertainties surrounding the use of this old drug and the derived benefits. Moreover, physicians who use mitotane should recognize and manage the systemic effects of the drug that need a complex supporting therapy. [ABSTRACT FROM AUTHOR]