Imaging studies are the cornerstone for tumor localization in patients with Cushing's syndrome caused by ectopic adrenocorticotropin hormone (ACTH) secretion (EAS). Computed tomography (CT) and magnetic resonance imaging (MRI) are used most commonly to localize the source of EAS. However, in 30-50 percent of patients with EAS the source of ACTH secretion cannot be found despite repeated studies over time. Up to half of these patients do not respond to medical therapy of hypercortisolism and must undergo bilateral adrenalectomy with lifelong replacement therapy. Thus, there is a need for improved imaging techniques to identify ACTH-secreting tumors. It is often difficult to find an adenoma in patients with Cushing's disease (CD) whose preoperative magnetic resonance imaging (MRI) is normal. Better localizing modalities are needed. We evaluated the utility of inferior petrosal sinus sampling (IPSS) to predict adenoma location. Potential false-negative results, the most common type of diagnostic error with IPSS for the differential diagnosis of CS, can be identified by peak IPSS ACTH values < 400 pg/ml. When MRI is normal, IPSS can be used to guide surgical exploration in patients with negative preoperative imaging. However, because of the limited accuracy of lateralization, thorough exploration of the pituitary gland is required when an adenoma is not readily discovered based on predicted location. The glucocorticoid antagonist mifepristone blocks cortisol action and thus might be an effective treatment of Cushing's syndrome. This hypothesis is being tested in an ongoing clinical trial of patients with presumed ectopic ACTH secretion. We have also observed that two individuals with a negative octreoscan initially converted that to a positive scan after mifepristone treatment.

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U.S. National Inst/Child Hlth/Human Dev
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Sharma, S T; Nieman, L K; Feelders, R A (2015) Comorbidities in Cushing's disease. Pituitary 18:188-94
Nieman, Lynnette K; Biller, Beverly M K; Findling, James W et al. (2015) Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100:2807-31
Sharma, Susmeeta T; Nieman, Lynnette K; Feelders, Richard A (2015) Cushing's syndrome: epidemiology and developments in disease management. Clin Epidemiol 7:281-93
Nieman, Lynette (2014) Pitfalls in the diagnosis and differential diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf) 80:333-4
Wind, Joshua J; Lonser, Russell R; Nieman, Lynnette K et al. (2013) The lateralization accuracy of inferior petrosal sinus sampling in 501 patients with Cushing's disease. J Clin Endocrinol Metab 98:2285-93
Lonser, Russell R; Wind, Joshua J; Nieman, Lynnette K et al. (2013) Outcome of surgical treatment of 200 children with Cushing's disease. J Clin Endocrinol Metab 98:892-901
Sharma, S T; Nieman, L K (2013) Is prolactin measurement of value during inferior petrosal sinus sampling in patients with adrenocorticotropic hormone-dependent Cushing's Syndrome? J Endocrinol Invest 36:1112-6
Nieman, Lynnette K (2013) Update in the medical therapy of Cushing's disease. Curr Opin Endocrinol Diabetes Obes 20:330-4
Abraham, Smita Baid; Abel, Brent S; Rubino, Domenica et al. (2013) A direct comparison of quality of life in obese and Cushing's syndrome patients. Eur J Endocrinol 168:787-93
Neary, Nicola M; Booker, O Julian; Abel, Brent S et al. (2013) Hypercortisolism is associated with increased coronary arterial atherosclerosis: analysis of noninvasive coronary angiography using multidetector computerized tomography. J Clin Endocrinol Metab 98:2045-52

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