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Cushing's disease: clinical manifestations and diagnostic evaluation.

The most common endogenous cause of Cushing's syndrome is Cushing's disease. Frequent clinical findings include weight gain, truncal obesity, striae, hypertension, glucose intolerance and infections. Cranial nerve II may be affected by enlarging pituitary adenomas in Cushing's disease; cranial nerves III, IV and VI may also be affected. The evaluation of patients with suspected Cushing's disease and syndrome requires an understanding of the proper use and limitations of the tests commonly included in the diagnostic work-up. The best screening test for Cushing's syndrome is a 24-hour urine collection with analysis for urinary free cortisol excretion. Low-dose and high-dose dexamethasone suppression tests, corticotropin assays, a corticotropin-releasing hormone stimulation test and inferior petrosal sinus catheterization may be required for a definitive diagnosis. Magnetic resonance imaging is useful in localizing the lesion. Surgical removal of the lesion by a transphenoidal approach is usually successful, but long-term follow-up is required. Some patients require lifetime glucocorticoid replacement therapy.