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The addition of corticotropin-releasing hormone to 2-day low dose dexamethasone suppression test provides additional case detection

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Purpose

The diagnostic value of adding a Corticotropin-Releasing Hormone (CRH) Stimulation Test to the 2-day Low Dose Dexamethasone Suppression Test (Dex-CRH Test) has been debated in the literature.

Methods

We identified 65 patients with Cushing disease (CD) and 42 patients in whom a diagnosis of Cushing disease could not be confirmed (NCD) after a minimum follow-up of 14 months who underwent the Dex-CRH test.

Results

The female sex ratio, median (range) age, and BMI were similar between the two groups. The follow-up for patients with CD and NCD was 74 (4–233) and 52 (14–146) months, respectively. Among 65 patients with CD, 5 (7.7%) had a cortisol level ≤1.4 µg/dl after LDDST but were appropriately classified as CD with a cortisol level >1.4 µg/dL at 15-min post CRH stimulation. In contrast, 3/42 patients (7.1%) in NCD had an abnormal Dex-CRH test. In only one of three patients, the LDDST was marginally normal (cortisol was 1.4 µg/dL and increased to 3.1 µg/dL 15-min post CRH). A cortisol cutoff value of >1.4 µg/dL during the Dex-CRH test provided a sensitivity of 100%, specificity of 93%, and diagnostic accuracy of 97% to diagnose CD. When patients without a Dex level were excluded (n = 74), the sensitivity did not change, but the specificity and accuracy of the Dex-CRH test increased to 97 and 99%, respectively.

Conclusion

The Dex-CRH Test provided additional case detection in 5/65 (7.7%) patients with CD. It resulted in one false-positive case compared to LDDST. Measurement of dexamethasone improved diagnostic accuracy of the test.

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References

  1. L.K. Nieman, B.M.K. Biller, J.W. Findling, J. Newell-Price, M.O. Savage, P.M. Stewart, H. Edwards, The diagnosis of Cushing’s syndrome: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 93(5), 1526–1540 (2008). https://doi.org/10.1210/jc.2008-0125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. J.W. Findling, H. Raff, Differentiation of pathologic/neoplastic hypercortisolism (Cushing’s syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing’s syndrome). Eur. J. Endocrinol. 176(5), R205–R216 (2017). https://doi.org/10.1530/EJE-16-0946

    Article  CAS  PubMed  Google Scholar 

  3. G.W. Liddle, Tests of pituitary-adrenal suppressibility in the diagnosis of cushing’s syndrome. J. Clin. Endocrinol. Metab. 20(12), 1539–1560 (1960). https://doi.org/10.1201/9781840765854

    Article  CAS  PubMed  Google Scholar 

  4. L. Kennedy, A.B. Atkinson, H. Johnston, B. Sheridan, D.R. Hadden, Serum cortisol concentrations during low dose dexamethasone suppression test to screen for Cushing’s syndrome. Brit. Med. J. 289, 1188–1191 (1984). https://doi.org/10.1136/bmj.289.6453.1188

    Article  CAS  Google Scholar 

  5. T.B. Kaye, L. Crapo, The Cushing syndrome: an update on diagnostic tests. Ann. Intern. Med. 112(6), 434–444 (1990). https://doi.org/10.7326/0003-4819-76-3-112-6-434

    Article  CAS  PubMed  Google Scholar 

  6. J. Newell-Price, P. Trainer, M. Besser, A. Grossman, The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr. Rev. 19(5), 647–672 (1998). https://academic.oup.com/edrv/article/19/5/647/2530832

    CAS  PubMed  Google Scholar 

  7. P. Wood, J. Barth, D. Freedman, L. Perry, B. Sheridan, Evidence for the low dose dexamethasone suppression test to screen for Cushing’s syndrome - recommendations for a protocol for biochemistry laboratories. Ann. Clin. Biochem 34, 222–229 (1997)

    Article  CAS  PubMed  Google Scholar 

  8. J.A. Yanovski, G.B. Cutler, G.P. Chrousos, L.K. Nieman, Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration. JAMA 269(17), 2232–2238 (1993). https://doi.org/10.1001/jama.1993.03500170062035

    Article  CAS  PubMed  Google Scholar 

  9. N.M. Martin, W.S. Dhillo, A. Banerjee, A. Abdulali, C.N. Jayasena, M. Donaldson, K. Meeran, Comparison of the dexamethasone-suppressed corticotropin-releasing hormone test and low-dose dexamethasone suppression test in the diagnosis of Cushing’s syndrome. J. Clin. Endocrinol. Metab. 91(7), 2582–2586 (2006). https://doi.org/10.1210/jc.2005-2143

    Article  CAS  PubMed  Google Scholar 

  10. D. Erickson, N. Natt, T. Nippoldt, W.F. Young, P.C. Carpenter, T. Petterson, T. Christianson, Dexamethasone-suppressed corticotropin-releasing hormone stimulation test for diagnosis of mild hypercortisolism. J. Clin. Endocrinol. Metab. 92(8), 2972–2976 (2007). https://doi.org/10.1210/jc.2006-2662

    Article  CAS  PubMed  Google Scholar 

  11. B. Gatta, O. Chabre, C. Cortet, M. Martinie, J.-B. Corcuff, P. Roger, A. Tabarin, Reevaluation of the combined dexamethasone suppression-corticotropin-releasing hormone test for differentiation of mild Cushing’s disease from pseudo-Cushing’s syndrome. J. Clin. Endocrinol. Metab. 92(11), 4290–4293 (2007). https://doi.org/10.1210/jc.2006-2829

    Article  CAS  PubMed  Google Scholar 

  12. F. Pecori Giraldi, R. Pivonello, A.G. Ambrogio, M.C. De Martino, M. De Martin, M. Scacchi, F. Cavagnini, The dexamethasone-suppressed corticotropin-releasing hormone stimulation test and the desmopressin test to distinguish Cushing’s syndrome from pseudo-Cushing’s states. Clin. Endocrinol. 66(2), 251–257 (2007). https://doi.org/10.1111/j.1365-2265.2006.02717.x

    Article  CAS  Google Scholar 

  13. R.A. Alwani, L.W.S. Jongbloed, F.H. De Jong, A.J. Van Der Lely, W.W. De Herder, R.A. Feelders, Differentiating between Cushing’s disease and pseudo-Cushing’s syndrome: comparison of four tests. Eur. J. Endocrinol. 170(4), 477–486 (2014). https://doi.org/10.1530/EJE-13-0702

    Article  CAS  PubMed  Google Scholar 

  14. M. Fleseriu, R. Auchus, I. Bancos, A. Ben-Shlomo, J. Bertherat, N.R. Biermasz, B.M. K Biller, Consensus on diagnosis and management of Cushing’s disease: a guideline update. Lancet Diabetes Endocrinol. 9, 847–875 (2021). https://doi.org/10.1016/S2213-8587(21)00235-7

    Article  PubMed  PubMed Central  Google Scholar 

  15. M.A. Magiakou, G. Mastorakos, E.H. Oldfield, M.T. Gomez, J.M. Dopman, G.B. Cutler Jr, G.P. Chrousos, Cushing’s syndrome in children and adolescents - presentation, diagnosis and therapy. N. Engl. J. Med. 331(10), 629–635 (1994)

    Article  CAS  PubMed  Google Scholar 

  16. J.A. Yanovski, G.B. Cutler, G.P. Chrousos, L.K. Nieman, The dexamethasone-suppressed corticotropin-releasing hormone stimulation test differentiates mild Cushing’s disease from normal physiology. J. Clin. Endocrinol. Metab. 83(2), 348–352 (1998). https://doi.org/10.1210/jc.2005-2143

    Article  CAS  PubMed  Google Scholar 

  17. G.Å. Ueland, P. Methlie, R. Kellmann, M. Bjørgaas, B.O. Åsvold, K. Thorstensen, E.S. Husebye, Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test. Eur. J. Endocrinol. 176(7), 705–713 (2017). https://doi.org/10.1530/EJE-17-0078

    Article  CAS  PubMed  Google Scholar 

  18. O. Orbach, G.C. Schussler, Increased serum cortisol binding in chronic active hepatitis. Am. J. Med. 86, 39–42 (1989). https://doi.org/10.1016/0002-9343(89)90227-1

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Johns Hopkins University, Baltimore, MD, USA

    Leen Wehbeh & Amir H. Hamrahian

  2. Department of Endocrinology, Endocrinology & Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA

    Ula Abed Alwahab, Alexandra Mikhael, Divya Yogi-Morren & Laurence Kennedy

  3. Departments of Neurosurgery and Endocrinology, Weill Cornell Medicine, New York, NY, USA

    Georgiana Dobri

Authors
  1. Leen Wehbeh
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  2. Ula Abed Alwahab
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  3. Alexandra Mikhael
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  6. Laurence Kennedy
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  7. Amir H. Hamrahian
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Contributions

L.W.: Preparation of the manuscript and data analysis; U.A.A. and A.M.: data collection and contributed to the manuscript, G.D., D.Y.-M., and L.K.: contributed patients to the study and edited the manuscript; A.H.H.: study design, patient contribution and supervising the preparation of the manuscript.

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Correspondence to Amir H. Hamrahian.

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Wehbeh, L., Alwahab, U.A., Mikhael, A. et al. The addition of corticotropin-releasing hormone to 2-day low dose dexamethasone suppression test provides additional case detection. Endocrine 80, 425–432 (2023). https://doi.org/10.1007/s12020-023-03327-5

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