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Submitted on May 8, 2006
Accepted on July 6, 2006
Endocrine-Diabetes Center, St. Luke's Medical Center, Milwaukee, WI 53215; Endocrine Research Laboratory, St. Luke's Medical Center, Milwaukee, WI 53215; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226
* To whom correspondence should be addressed. E-mail: hraff{at}mcw.edu.
Context: The diagnosis, differential diagnosis, and treatment of Cushing's syndrome are challenging problems in clinical endocrinology. We focus on critical questions addressing screening for Cushing's syndrome, differentiation of Cushing's subtypes, and treatment options.
Evidence Acquisition: Ovid Medline (1996-April 2006) was used to search the general literature. We also relied on previously published reviews, a recent monograph and cite a mix of primary articles and recent reviews.
Evidence Synthesis: Although this article represents our opinion, it draws heavily on a recent consensus statement from experts in the field (J Clin Endocrinol Metab 2003;88:5593-602) and a recent monograph on Cushing's syndrome (Endocrinol Metab Clin N Am. June 2005, Vol 34, Number 2, Saunders, Philadelphia, 2005).
Conclusions: (1) Measurement of late-night or bedtime salivary cortisol is a useful approach to screen for Cushing's syndrome (2). Measurement of suppressed plasma ACTH by immunometric assay is useful to differentiate ACTH-dependent and independent Cushing's syndrome (3). Inferior petrosal sinus sampling for ACTH should be performed in patients with ACTH-dependent hypercortisolism in whom a pituitary MRI is normal or equivocal. In the absence of a pituitary ACTH gradient, prolactin levels should be measured to confirm the integrity of venous sampling (4). Computed tomography of the chest and abdomen and somatostatin-receptor scintigraphy should be performed in patients the occult ectopic ACTH syndrome (5). Patients with Cushing's disease should be referred to a neurosurgeon with extensive experience operating on corticotroph microadenomas. Bilateral laparoscopic adrenalectomy should be considered in patients with Cushing's disease who fail therapies directed at the pituitary.
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