This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Findling, J. W. Articles by Raff, H. Search for Related Content PubMed PubMed Citation Articles by Findling, J. W. Articles by Raff, H. Related Collections Adrenal and Hypertension Neuroendocrinology and Pituitary Endocrine Oncology

Cushing’s Syndrome: Important Issues in Diagnosis and Management

Endocrine-Diabetes Center (J.W.F.) and Endocrine Research Laboratory (H.R.), St. Luke’s Medical Center, Milwaukee, Wisconsin 53215; and Department of Medicine (J.W.F., H.R.), Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Address all correspondence and requests for reprints to: Hershel Raff, Ph.D., Endocrinology, St. Luke’s Physician’s Office Building, 2801 West KK River Parkway, Suite 245, Milwaukee, Wisconsin 53215. 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’s MEDLINE (1996 through April 2006) was used to search the general literature. We also relied on previously published reviews and 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 and a recent monograph on Cushing’s syndrome.

Conclusions: We concluded that: 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 magnetic resonance imaging 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 with the occult ectopic ACTH syndrome; and 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.

This article has been cited by other articles:

				E. Valassi, B. Swearingen, H. Lee, L. B. Nachtigall, D. A. Donoho, A. Klibanski, and B. M. K. Biller Concomitant Medication Use Can Confound Interpretation of the Combined Dexamethasone-Corticotropin Releasing Hormone Test in Cushing's Syndrome J. Clin. Endocrinol. Metab., December 1, 2009; 94(12): 4851 - 4859. [Abstract] [Full Text] [PDF]

				A. Takeshita, N. Inoshita, M. Taguchi, C. Okuda, N. Fukuhara, K. Oyama, K. Ohashi, T. Sano, Y. Takeuchi, and S. Yamada High incidence of low O6-methylguanine DNA methyltransferase expression in invasive macroadenomas of Cushing's disease Eur. J. Endocrinol., October 1, 2009; 161(4): 553 - 559. [Abstract] [Full Text] [PDF]

				H. Raff Utility of Salivary Cortisol Measurements in Cushing's Syndrome and Adrenal Insufficiency J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 3647 - 3655. [Abstract] [Full Text] [PDF]

				M. Boscaro and G. Arnaldi Approach to the Patient with Possible Cushing's Syndrome J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3121 - 3131. [Abstract] [Full Text] [PDF]

				P. Wood Salivary steroid assays - research or routine? Ann Clin Biochem, May 1, 2009; 46(3): 183 - 196. [Abstract] [Full Text] [PDF]

				A. C Heijboer, F. Martens, and M. A Blankenstein Measuring salivary cortisol with the Architect i2000 random access analyser Ann Clin Biochem, May 1, 2009; 46(3): 261 - 262. [Full Text] [PDF]

				B. Masserini, V. Morelli, S. Bergamaschi, F. Ermetici, C. Eller-Vainicher, A. M. Barbieri, M. A. Maffini, A. Scillitani, B. Ambrosi, P. Beck-Peccoz, et al. The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma Eur. J. Endocrinol., January 1, 2009; 160(1): 87 - 92. [Abstract] [Full Text] [PDF]

				S. Jehle, J. E. Walsh, P. U. Freda, and K. D. Post Selective Use of Bilateral Inferior Petrosal Sinus Sampling in Patients with Adrenocorticotropin-Dependent Cushing's Syndrome Prior to Transsphenoidal Surgery J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4624 - 4632. [Abstract] [Full Text] [PDF]

				E. Singer, S. Strohm, U. Gobel, M. Bieringer, D. Schmidt, W. Schneider, R. Kettritz, and F. C. Luft Cushing's Disease, Hypertension, and Other Sequels Hypertension, December 1, 2008; 52(6): 1001 - 1005. [Full Text] [PDF]

				P. Burman, A. Lethagen, K. Ivancev, L. Johansson, and A. Sundin Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to dexamethasone and a false positive outcome of inferior petrosal sinus sampling Eur. J. Endocrinol., October 1, 2008; 159(4): 483 - 488. [Abstract] [Full Text] [PDF]

				J. Moreno-Fernandez, C. Gutierrez-Alcantara, M. A. Galvez Moreno, L. Jimenez-Reina, J. P. Castano, and P. Benito-Lopez Corticotrophin-Dependent Cushing Syndrome Due to Sacrococcygeal Teratoma Detected by [18F]Fluorodeoxyglucose Positron Emission Tomography J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3282 - 3283. [Full Text] [PDF]

				L. Wood, D. H Ducroq, H. L Fraser, S. Gillingwater, C. Evans, A. J Pickett, D. W Rees, R. John, and A. Turkes Measurement of urinary free cortisol by tandem mass spectrometry and comparison with results obtained by gas chromatography-mass spectrometry and two commercial immunoassays Ann Clin Biochem, July 1, 2008; 45(4): 380 - 388. [Abstract] [Full Text] [PDF]

				B. M. K. Biller, A. B. Grossman, P. M. Stewart, S. Melmed, X. Bertagna, J. Bertherat, M. Buchfelder, A. Colao, A. R. Hermus, L. J. Hofland, et al. Treatment of Adrenocorticotropin-Dependent Cushing's Syndrome: A Consensus Statement J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2454 - 2462. [Abstract] [Full Text] [PDF]

				P. C. Myhill, B. A. Sillars, S. Starkstein, T. Annus, and B. B. Yeap Reduction in Salivary Cortisol Concentration Correlates with Resolution of Psychosis in Cushing's Syndrome J Neuropsychiatry Clin Neurosci, February 1, 2008; 20(1): 113 - 115. [Full Text] [PDF]

				S. Kidambi, H. Raff, and J. W Findling Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome Eur. J. Endocrinol., December 1, 2007; 157(6): 725 - 731. [Abstract] [Full Text] [PDF]

				S. K. Baid, N. Sinaii, M. Wade, D. Rubino, and L. K. Nieman Radioimmunoassay and Tandem Mass Spectrometry Measurement of Bedtime Salivary Cortisol Levels: A Comparison of Assays to Establish Hypercortisolism J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3102 - 3107. [Abstract] [Full Text] [PDF]

				Authors/Task Force Members:, G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A. M. Heagerty, S. E. Kjeldsen, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur. Heart J., June 11, 2007; (2007) ehm236v1. [Full Text] [PDF]

				S. Tsagarakis, D. Vassiliadi, I. S. Kaskarelis, J. Komninos, E. Souvatzoglou, and N. Thalassinos The Application of the Combined Corticotropin-Releasing Hormone plus Desmopressin Stimulation during Petrosal Sinus Sampling Is Both Sensitive and Specific in Differentiating Patients with Cushing's Disease from Patients with the Occult Ectopic Adrenocorticotropin Syndrome J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2080 - 2086. [Abstract] [Full Text] [PDF]