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High-dose dexamethasone suppression test is inferior to pituitary dynamic enhanced MRI in the differential diagnosis of ACTH-dependent Cushing’s syndrome

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Abstract

Purpose

The differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome remains a challenge in clinical practice. The present study was aimed at assessing the diagnostic performance of pituitary dynamic contrast-enhanced magnetic resonance imaging (dMRI), high-dose dexamethasone suppression test (HDDST), and a combination of both tests for patients with ACTH-dependent Cushing’s syndrome.

Methods

A total of 119 consecutive patients with ACTH-dependent Cushing’s syndrome confirmed surgically were enrolled: 101 with proven Cushing’s disease and 18 with proven ectopic ACTH syndrome. All patients underwent pituitary dMRI and HDDST. The sensitivity and specificity of pituitary dMRI, HDDST, and a combination of both tests were determined.

Results

The sensitivity and specificity of pituitary dMRI for diagnosing Cushing’s disease were 80.2 and 83.3%, respectively, with a positive predictive value of 96.4%. The sensitivity and specificity of HDDST were 70.3 and 77.8%, respectively, with positive predictive value of 94.7%. A combination of both tests showed that the combined criteria of more than 50% suppression of serum cortisol on HDDST and a positive pituitary dMRI finding yielded a high specificity of 94.4 and sensitivity of 59.4%. The combined criteria of more than 68% suppression on HDDST and/or a positive pituitary dMRI finding yielded a sensitivity of 86.1% and specificity of 83.3%.

Conclusions

Pituitary dMRI was superior to HDDST in the differential diagnosis of ACTH-dependent Cushing’s syndrome. HDDST is recommended in combination with pituitary dMRI to establish a diagnosis process because of the significantly increased specificity with the combination.

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Abbreviations

CS:

Cushing’s syndrome

ACTH:

adrenocorticotropic hormone

CD:

Cushing’s disease

EAS:

ectopic ACTH syndrome

dMRI:

dynamic contrast-enhanced magnetic resonance imaging

HDDST:

high-dose dexamethasone suppression test

BIPSS:

bilateral inferior petrosal sinus sampling

CRH:

corticotrophin-releasing hormone

PET:

positron emission tomography.

References

  1. F. Pecori Giraldi, L.M. Cavallo, F. Tortora, R. Pivonello, A. Colao, P. Cappabianca, F. Mantero, The role of inferior petrosal sinus sampling in ACTH-dependent Cushing’s syndrome: review and joint opinion statement by members of the Italian Society for Endocrinology, Italian Society for Neurosurgery, and Italian Society for Neuroradiology. Neurosurgical focus 38(2), E5 (2015). https://doi.org/10.3171/2014.11.Focus14766

    Article  PubMed  Google Scholar 

  2. M. Barbot, L. Trementino, M. Zilio, F. Ceccato, N. Albiger, A. Daniele, A.C. Frigo, R. Mardari, G. Rolma, M. Boscaro, G. Arnaldi, C. Scaroni, Second-line tests in the differential diagnosis of ACTH-dependent Cushing’s syndrome. Pituitary 19(5), 488–495 (2016). https://doi.org/10.1007/s11102-016-0729-y

    Article  CAS  PubMed  Google Scholar 

  3. G. Reimondo, P. Paccotti, M. Minetto, A. Termine, G. Stura, M. Bergui, A. Angeli, M. Terzolo, The corticotrophin-releasing hormone test is the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing’s syndrome. Clin. Endocrinol. 58(6), 718–724 (2003). https://doi.org/10.1046/j.1365-2265.2003.01776.x

    Article  CAS  Google Scholar 

  4. M. Terzolo, G. Reimondo, A. Alì, G. Borretta, F. Cesario, A. Pia, P. Paccotti, A. Angeli, The limited value of the desmopressin test in the diagnostic approach to Cushing’s syndrome. Clin. Endocrinol. 54(5), 609–616 (2001). https://doi.org/10.1046/j.1365-2265.2001.01260.x

    Article  CAS  Google Scholar 

  5. Nishioka, H., Yamada, S.: Cushing’s Disease. Journal of clinical medicine 8(11) (2019). https://doi.org/10.3390/jcm8111951

  6. I.S. Kaskarelis, E.G. Tsatalou, S.V. Benakis, K. Malagari, I. Komninos, D. Vassiliadi, S. Tsagarakis, N. Thalassinos, Bilateral inferior petrosal sinuses sampling in the routine investigation of Cushing’s syndrome: a comparison with MRI. Ajr. Am. J. Roentgenol. 187(2), 562–570 (2006). https://doi.org/10.2214/ajr.05.0557

    Article  PubMed  Google Scholar 

  7. G. Vitale, F. Tortora, R. Baldelli, F. Cocchiara, R.M. Paragliola, E. Sbardella, C. Simeoli, F. Caranci, R. Pivonello, A. Colao, Pituitary magnetic resonance imaging in Cushing’s disease. Endocrine 55(3), 691–696 (2017). https://doi.org/10.1007/s12020-016-1038-y

    Article  CAS  PubMed  Google Scholar 

  8. T.C. Friedman, E. Zuckerbraun, M.L. Lee, M.S. Kabil, H. Shahinian, Dynamic pituitary MRI has high sensitivity and specificity for the diagnosis of mild Cushing’s syndrome and should be part of the initial workup. Horm. Metab. Res. = Horm.- und Stoffwechselforschung = Hormones et. Metab. 39(6), 451–456 (2007). https://doi.org/10.1055/s-2007-980192

    Article  CAS  Google Scholar 

  9. L.K. Nieman, B.M. Biller, J.W. Findling, J. Newell-Price, M.O. Savage, P.M. Stewart, V.M. Montori, 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 

  10. J.F. Bonneville, F. Bonneville, F. Cattin, Magnetic resonance imaging of pituitary adenomas. Eur. Radiol. 15(3), 543–548 (2005). https://doi.org/10.1007/s00330-004-2531-x

    Article  PubMed  Google Scholar 

  11. L.K. Nieman, B.M. Biller, J.W. Findling, M.H. Murad, J. Newell-Price, M.O. Savage, A. Tabarin, Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 100(8), 2807–2831 (2015). https://doi.org/10.1210/jc.2015-1818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. S. Jehle, J.E. Walsh, P.U. Freda, 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. 93(12), 4624–4632 (2008). https://doi.org/10.1210/jc.2008-0979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. P. Bansal, A. Lila, M. Goroshi, S. Jadhav, N. Lomte, K. Thakkar, A. Goel, A. Shah, S. Sankhe, N. Goel, N. Jaguste, T. Bandgar, N. Shah, Duration of post-operative hypocortisolism predicts sustained remission after pituitary surgery for Cushing’s disease. Endocr. Connect. 6(8), 625–636 (2017). https://doi.org/10.1530/ec-17-0175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. M. Boscaro, G. Arnaldi, Approach to the patient with possible Cushing’s syndrome. J. Clin. Endocrinol. Metab. 94(9), 3121–3131 (2009). https://doi.org/10.1210/jc.2009-0612

    Article  CAS  PubMed  Google Scholar 

  15. N. Colombo, P. Loli, F. Vignati, G. Scialfa, MR of corticotropin-secreting pituitary microadenomas. Ajnr. Am. J. Neuroradiol. 15(8), 1591–1595 (1994)

    CAS  PubMed  PubMed Central  Google Scholar 

  16. A. Lienhardt, A.B. Grossman, J.E. Dacie, J. Evanson, A. Huebner, F. Afshar, P.N. Plowman, G.M. Besser, M.O. Savage, Relative contributions of inferior petrosal sinus sampling and pituitary imaging in the investigation of children and adolescents with ACTH-dependent Cushing’s syndrome. J. Clin. Endocrinol. Metab. 86(12), 5711–5714 (2001). https://doi.org/10.1210/jcem.86.12.8086

    Article  CAS  PubMed  Google Scholar 

  17. A. Tabarin, F. Laurent, B. Catargi, F. Olivier-Puel, R. Lescene, J. Berge, F.S. Galli, J. Drouillard, P. Roger, J. Guerin, Comparative evaluation of conventional and dynamic magnetic resonance imaging of the pituitary gland for the diagnosis of Cushing’s disease. Clin. Endocrinol. 49(3), 293–300 (1998). https://doi.org/10.1046/j.1365-2265.1998.00541.x

    Article  CAS  Google Scholar 

  18. V. Lefournier, M. Martinie, A. Vasdev, P. Bessou, J.G. Passagia, F. Labat-Moleur, N. Sturm, J.L. Bosson, I. Bachelot, O. Chabre, Accuracy of bilateral inferior petrosal or cavernous sinuses sampling in predicting the lateralization of Cushing’s disease pituitary microadenoma: influence of catheter position and anatomy of venous drainage. J. Clin. Endocrinol. Metab. 88(1), 196–203 (2003). https://doi.org/10.1210/jc.2002-020374

    Article  CAS  PubMed  Google Scholar 

  19. K.E. Graham, M.H. Samuels, G.M. Nesbit, D.M. Cook, O.R. O’Neill, S.L. Barnwell, D.L. Loriaux, Cavernous sinus sampling is highly accurate in distinguishing Cushing’s disease from the ectopic adrenocorticotropin syndrome and in predicting intrapituitary tumor location. J. Clin. Endocrinol. Metab. 84(5), 1602–1610 (1999). https://doi.org/10.1210/jcem.84.5.5654

    Article  CAS  PubMed  Google Scholar 

  20. Z. Liu, X. Zhang, Z. Wang, H. You, M. Li, F. Feng, Z. Jin, High positive predictive value of the combined pituitary dynamic enhanced MRI and high-dose dexamethasone suppression tests in the diagnosis of Cushing’s disease bypassing bilateral inferior petrosal sinus sampling. Sci. Rep. 10(1), 14694 (2020). https://doi.org/10.1038/s41598-020-71628-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Frete, C., Corcuff, J.B., Kuhn, E., Salenave, S., Gaye, D., Young, J., Chanson, P., Tabarin, A.: Non-invasive Diagnostic Strategy in ACTH-dependent Cushing’s Syndrome. The Journal of clinical endocrinology and metabolism 105(10) (2020). https://doi.org/10.1210/clinem/dgaa409

  22. L.K. Nieman, Is it Time for a New Approach to the Differential Diagnosis of ACTH-Dependent Cushing Syndrome? J. Clin. Endocrinol. Metab. 105(12), e4964–4966 (2020). https://doi.org/10.1210/clinem/dgaa493

    Article  PubMed Central  Google Scholar 

  23. D.C. Aron, H. Raff, J.W. Findling, Effectiveness versus efficacy: the limited value in clinical practice of high dose dexamethasone suppression testing in the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J. Clin. Endocrinol. Metab. 82(6), 1780–1785 (1997). https://doi.org/10.1210/jcem.82.6.3991

    Article  CAS  PubMed  Google Scholar 

  24. X. Bertagna, L. Guignat, L. Groussin, J. Bertherat, Cushing’s disease. Best practice & research. Clin. Endocrinol. Metab. 23(5), 607–623 (2009). https://doi.org/10.1016/j.beem.2009.06.001

    Article  CAS  Google Scholar 

  25. R.R. Lonser, L. Nieman, E.H. Oldfield, Cushing’s disease: pathobiology, diagnosis, and management. J. Neurosurg. 126(2), 404–417 (2017). https://doi.org/10.3171/2016.1.Jns152119

    Article  PubMed  Google Scholar 

  26. W. Zhang, Y. Yu, H. Tan, C. Wang, J. Li, Z. An, Y. Liu, [Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing’s syndrome]. Zhonghua yi xue za zhi 96(11), 845–849 (2016). https://doi.org/10.3760/cma.j.issn.0376-2491.2016.11.004

    Article  CAS  PubMed  Google Scholar 

  27. A. Colao, A. Faggiano, R. Pivonello, F. Pecori Giraldi, F. Cavagnini, G. Lombardi, Inferior petrosal sinus sampling in the differential diagnosis of Cushing’s syndrome: results of an Italian multicenter study. Eur. J. Endocrinol. 144(5), 499–507 (2001). https://doi.org/10.1530/eje.0.1440499

    Article  CAS  PubMed  Google Scholar 

  28. B. Swearingen, L. Katznelson, K. Miller, S. Grinspoon, A. Waltman, D.J. Dorer, A. Klibanski, B.M. Biller, Diagnostic errors after inferior petrosal sinus sampling. J. Clin. Endocrinol. Metab. 89(8), 3752–3763 (2004). https://doi.org/10.1210/jc.2003-032249

    Article  CAS  PubMed  Google Scholar 

  29. P. Grant, D. Dworakowska, P. Carroll, Maximizing the accuracy of Inferior petrosal sinus sampling: validation of the use of Prolactin as a marker of pituitary venous effluent in the diagnosis of Cushing’s disease. Clin. Endocrinol. 76(4), 555–559 (2012). https://doi.org/10.1111/j.1365-2265.2011.04257.x

    Article  CAS  Google Scholar 

  30. B. Zampetti, E. Grossrubatscher, P. Dalino Ciaramella, E. Boccardi, P. Loli, Bilateral inferior petrosal sinus sampling. Endocr. Connect. 5(4), R12–25 (2016). https://doi.org/10.1530/ec-16-0029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. E. Valassi, B. Swearingen, H. Lee, L.B. Nachtigall, D.A. Donoho, A. Klibanski, B.M. Biller, Concomitant medication use can confound interpretation of the combined dexamethasone-corticotropin releasing hormone test in Cushing’s syndrome. J. Clin. Endocrinol. Metab. 94(12), 4851–4859 (2009). https://doi.org/10.1210/jc.2009-1500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. F. Ceccato, C. Artusi, M. Barbot, L. Lizzul, S. Pinelli, G. Costantini, S. Niero, G. Antonelli, M. Plebani, C. Scaroni, Dexamethasone measurement during low-dose suppression test for suspected hypercortisolism: threshold development with and validation. J. endocrinological Investig. 43(8), 1105–1113 (2020). https://doi.org/10.1007/s40618-020-01197-6

    Article  CAS  Google Scholar 

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Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 81800686) and the Science and Technology Program of Hubei Province (No. 2019CFB316).

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Author notes

  1. These authors contributed equally: Juan Chen, Yan Yang

Authors and Affiliations

  1. Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P.R. China

    Xiaoli Shi, Tingting Du, Dan Zhu, Delin Ma, Kun Dong, Xuemin Peng, Jiaojiao Huang, Xuefeng Yu & Yan Yang

  2. Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, Hubei, P.R. China

    Xiaoli Shi, Tingting Du, Dan Zhu, Delin Ma, Kun Dong, Xuemin Peng, Jiaojiao Huang, Xuefeng Yu & Yan Yang

  3. Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P.R. China

    Ting Lei & Juan Chen

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  1. Xiaoli Shi
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Correspondence to Juan Chen or Yan Yang.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Shi, X., Du, T., Zhu, D. et al. High-dose dexamethasone suppression test is inferior to pituitary dynamic enhanced MRI in the differential diagnosis of ACTH-dependent Cushing’s syndrome. Endocrine 75, 516–524 (2022). https://doi.org/10.1007/s12020-021-02891-y

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