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.