Study of Adrenalectomy Versus Observation for Subclinical Hypercortisolism

Background: * Adrenal incidentalomas are common and found in approximately 4-7% of the population. * About 0.6 to 25% of patients with an adrenal incidentaloma are found to have subclinical hypercortisolism: 2.3% develop subclinical hypercortisolism during follow up and 0.6% develop clinical hypercortisolism during follow up. * Subclinical hypercortisolism is defined as biochemical excess of cortisol without signs and symptoms of overt hypercortisolism but may be associated with metabolic complications or disease progression and malignancy. * Overt signs and symptoms of hypercortisolism include facial plethora, easy bruising, violaceous striae, and proximal muscle weakness. * Several studies suggest that subclinical hypercortisolism may lead to long term consequences such as diabetes, hypertension, hypercholesterolemia, obesity, and osteoporosis. * Thus, patients with subclinical hypercortisolism may benefit from operative intervention to halt or reverse metabolic complications associated with the disease and the risk of malignant progression. * The optimal management of patients with subclinical hypercortisolism and adrenal incidentalomas is controversial and no large randomized trial has been conducted. * We hypothesize that operative treatment would reduce the risk of long term complications of subclinical hypercortisolism and malignant progression, and propose a prospective randomized trial comparing nonoperative and operative management of subclinical hypercortisolism in patients with an adrenal neoplasm. Objectives: Primary Endpoints: -To determine whether unilateral adrenalectomy in patients diagnosed with subclinical hypercortisolism and adrenal neoplasm results in normalization and/or improvement of hypertension as assessed by reduction in pharmacotherapy and/or normalization of blood pressure (systolic pressure \<=140 and diastolic pressure \<=90), diabetes as assessed by reduction or elimination of pharmacotherapy and/or improvement in A1C to \<6.5%, osteoporosis by increase in bone formation markers indicative of increased bone formation, hypercholesterolemia as assessed by a reduction or elimination of pharmacotherapy and/or reduction in low density lipoprotein (LDL) levels to risk-stratified goal levels as defined by Adult Treatment Panel III (ATP III), and/or overweight or obesity as assessed by a 10 percent reduction in weight at 6 months. Eligibility: * An individual with an adrenal neoplasm less than 5 cm in size with biochemically confirmed evidence of hypercortisolism (2 out of 3: dexamethasone suppression test (DST) \>3 mcgl/dL, elevated urine free cortisol, and/or morning adrenocorticotrophic hormone (ACTH) \<2.2 pmol/l) without overt clinical signs and symptoms. * Age greater than or equal to 18 years. * Adults must be able to understand and sign the informed consent document. * Patients must have laboratory and physical examination parameters within acceptable limits based on standard clinical practice. Design: * Prospective randomized study comparing adrenalectomy versus observation. * Patients assigned to the operative arm will undergo adrenalectomy and then followed postoperatively for normalization and/or improvement of metabolic complications associated with hypercortisolism and histologic examination of the resected tumor. * Patients assigned to the non-operative arm will be monitored for possible complications associated with hypercortisolism for six months, at which point they will cross-over to the operative intervention arm. * Patients with bilateral adrenal neoplasms will have the larger adrenal neoplasm used as the primary lesion responsible for subclinical hypercortisolism. * Demographic, clinical, laboratory and pathologic data will be collected for each patient participant. Data will be securely stored in a computerized database. * Patients will have biochemical testing to determine if their adrenal neoplasm is functioning or nonfunctioning. * Projected accrual will be 15 to 20 patients per year for a total of 5 years. Thus, we anticipate accruing 62 patients on this protocol.