Current strategies for the treatment of severe Cushing's syndrome

Severe Cushing's syndrome may present an acute emergency in patients diagnosed with Cushing's syndrome with recent onset of at least one of the following: sepsis, opportunistic infection; intractable hypokalaemia, uncontrolled hypertension; heart failure; gastrointestinal hemorrhage; acute psychosis; progressive debilitating myopathy; thromboembolism; uncontrolled hyperglycemia and ketoacidosis. The biochemical definition includes serum cortisol ≥41μg/dl (1100 nmol/l) and/or severe hypokalemia (<3.0 mmol/l) or urine free cortisol fivefold the upper limit of normal. Treatment focuses on the management of severe metabolic disturbances followed by rapid resolution of the hypercortisolemia and subsequent confirmation of the cause. We emphasize the control of the hypokalemia, hypertension, diabetes and any psychotic state, anti-coagulation, monitoring and vigorous therapy of opportunistic infections. The ideal first-line therapies include metyrapone and ketoconazole, followed by parenteral etomidate; if all else fails life-saving bilateral adrenalectomy should be considered.