Advertisement

Pituitary

pp 1–7 | Cite as

Prediction of recurrence and remission within 3 years in patients with Cushing disease after successful transnasal adenomectomy

  • Elena Y. NadezhdinaEmail author
  • Olga Yu. Rebrova
  • Andrey Y. Grigoriev
  • Oksana V. Ivaschenko
  • Vilen N. Azizyan
  • Galina A. Melnichenko
  • Ivan I. Dedov
Article

Abstract

Background

Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier.

Aim

To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD.

Methods

Retrospective single-site comparative study included 349 patients (52 men and 297 women) with a verified diagnosis of CD who underwent effective endoscopic transsphenoidal adenomectomy between 2007 and 2014. Clinical and laboratory parameters were evaluated. Laboratory tests were performed using immunochemiluminescent method. Time-to-event analysis and ROC-analysis were applied. Multivariate models were developed using logistic regression and artificial neural network (ANN).

Results

Postoperative cortisol and ACTH levels and their combinations cannot be used for prediction of recurrence. ANN for prediction of recurrence within 3 years after successful surgery was developed. Input variables are age, duration of the disease, MRI data on adenoma, morning postoperative levels of ACTH and cortisol, output variable is binary (recurrence/remission). Predictive value for remission is 93%, 95% CI [89%; 96%], and predictive value for recurrence is 85%, 95% CI [71%; 94%]. Web-calculator based on the model is developed and free for use.

Conclusion

Effective method for prediction of recurrence and long-term remission within 3 years after successful endoscopic transsphenoidal adenomectomy is proposed.

Keywords

Cushing disease Neuroendoscopy Pituitary ACTH hypersecretion Recurrence Remission Prediction Neural network Web calculator 

Notes

Acknowledgements

The authors thank M.S. Antyukh for programming the web calculator.

Compliance with ethical standards

Conflict of interest

All authors on this manuscript have declared that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Local Ethical Committee of the Endocrinology Research Centre.

References

  1. 1.
    Biller B, Grossman A, Stewart P et al (2008) Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. Clin Endocrinol Metab 93:2454–2462.  https://doi.org/10.1210/jc.2007-2734 CrossRefGoogle Scholar
  2. 2.
    Nieman L, Biller B, Findling J et al (2015) Treatment of Cushing’s syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 100(8):2807–2831.  https://doi.org/10.1210/jc.2015-1818 CrossRefGoogle Scholar
  3. 3.
    Bochicchio D, Losa M, Buchfelder M (1995) Factors influencing the immediate and late outcome of Cushing’s disease treated by transsphenoidal surgery: a retrospective study by the European Cushing’s Disease Survey Group. J Clin Endocrinol Metab 80:3114–3120.  https://doi.org/10.1210/jcem.80.11.7593411 Google Scholar
  4. 4.
    Hameed N, Yedinak CG, Brzana J et al (2013) Remission rate after transsphenoidal surgery in patients with pathologically confirmed Cushing’s disease, the role of cortisol, ACTH assessment and immediate reoperation: a large single center experience. Pituitary 16:452–458.  https://doi.org/10.1007/s11102-012-0455-z CrossRefGoogle Scholar
  5. 5.
    McCance D, Gordon D, Fannin T et al (1993) Assessment of endocrine function after transsphenoidal surgery for Cushing’s disease. Clin Endocrinol (Oxf) 38:79–86.  https://doi.org/10.1111/j.1365-2265.1993.tb00976.x CrossRefGoogle Scholar
  6. 6.
    van Aken M, de Herder W, van der Lely A et al (1997) Postoperative metyrapone test in the early assessment of outcome of pituitary surgery for Cushing’s disease. Clin Endocrinol (Oxf) 47:145–149.  https://doi.org/10.1046/j.1365-2265.1997.2541051.x CrossRefGoogle Scholar
  7. 7.
    Shimon I, Ram Z, Cohen Z et al (2002) Transsphenoidal surgery for Cushing’s disease: endocrinological follow-up monitoring of 82 patients. Neurosurgery 51(1):57–61.  https://doi.org/10.1210/er.2013-1048 CrossRefGoogle Scholar
  8. 8.
    Alexandraki K, Kaltsas G, Isidori A et al (2013) Long-term remission and recurrence rates in Cushing’s disease: predictive factors in a single-centre study. Eur J Endocrinol 168:639–648.  https://doi.org/10.1530/EJE-12-0921 CrossRefGoogle Scholar
  9. 9.
    Aranda G, Enseñat J, Mora M et al (2015) Long-term remission and recurrence rate in a cohort of Cushing’s disease: the need for long-term follow-up. Pituitary 18:142–149.  https://doi.org/10.1007/s11102-014-0567-8 CrossRefGoogle Scholar
  10. 10.
    Barbetta L, Dall’Asta C, Tomei G et al (2001) Assessment of cure and recurrence after pituitary surgery for Cushing’s disease. Acta Neurochir (Wien) 143:477–482.  https://doi.org/10.1007/S007010170077 CrossRefGoogle Scholar
  11. 11.
    Petersenn S, Beckers A, Ferone D et al (2015) Therapy of endocrine disease: outcomes in patients with Cushing’s disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence. Eur J Endocrinol 172(6):227–239.  https://doi.org/10.1530/EJE-14-0883 CrossRefGoogle Scholar
  12. 12.
    Lonser R, Nieman L, Oldfield E (2017) Cushing’s disease: pathobiology, diagnosis, and management. J Neurosurg 126(2):404–417.  https://doi.org/10.3171/2016.1.JNS152119 CrossRefGoogle Scholar
  13. 13.
    Kim J, Shin C, Paek S et al (2012) Recurrence of Cushing’s disease after primary transsphenoidal surgery in a university hospital in Korea. Endocr J 59(10):881–888.  https://doi.org/10.1507/endocrj.EJ12-0109 CrossRefGoogle Scholar
  14. 14.
    Dedov II, Melnichenko GA (eds) (2016) Russian clinical guidelines. Endocrinology, Moscow (in Russian)Google Scholar
  15. 15.
    Pettersen J, Halvorsen H, Evang J et al (2015) Low immediate postoperative serum-cortisol Nadir predicts the short-term, but not long-term, remission after pituitary surgery for Cushing’s disease. BMC Endocr Disord 15:62.  https://doi.org/10.1186/s12902-015-0055-9 CrossRefGoogle Scholar
  16. 16.
    Marova E., Arapova S, Belaya Z et al (2012) Cushing’s disease: the clinical features, diagnostics, treatment. In: Dedov, II, Melnichenko GA (eds) Practical guide for doctors. Moscow, pp 2–32 (in Russian)Google Scholar
  17. 17.
    Melnichenko G, Dedov I, Belaya Z et al (2015) Cushing’s disease: the clinical features, diagnostics, differential diagnostics, and methods of treatment. Probl Endocrinol 61(2):55–77.  https://doi.org/10.14341/probl201561255-77 (in Russian)CrossRefGoogle Scholar
  18. 18.
    Roelfsema F, Biermasz N, Pereira A et al (2012) Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis. Pituitary 15(1):71–83.  https://doi.org/10.1007/s11102-011-0347-7 CrossRefGoogle Scholar
  19. 19.
    Dickerman R, Oldfield E (2002) Basis of persistent and recurrent Cushing disease: an analysis of findings at repeated pituitary surgery. Neurosurgery 97(6):1343–1349.  https://doi.org/10.3171/jns.2002.97.6.1343 CrossRefGoogle Scholar
  20. 20.
    Oldfield E (2011) Surgical management of Cushing’s disease: a personal perspective. Clin Neurosurg 58:13–26.  https://doi.org/10.1227/neu.0b013e3182269d3f CrossRefGoogle Scholar
  21. 21.
    Wislocky G (1938) The vascular supply of the hypophysis cerebri of the Rhesus monkey and man. Proc Assoc Res Ment Dis 17:48–68Google Scholar
  22. 22.
    Burke W, Penn D, Repetti C et al (2019) Outcomes after repeat transsphenoidal surgery for recurrent Cushing disease: updated. Neurosurgery.  https://doi.org/10.1093/neuros/nyz193 Google Scholar
  23. 23.
    Jagannathan J, Smith R, DeVroom H (2009) Outcome of using the histological pseudocapsule as a surgical capsule in Cushing disease. J Neurosurg 111(3):531–539.  https://doi.org/10.3171/2008.8.JNS08339 CrossRefGoogle Scholar
  24. 24.
    Dallapiazza R, Oldfield E, Jane J (2015) Surgical management of Cushing’s disease. Pituitary 18(2):211–216.  https://doi.org/10.1007/s11102-015-0646-5 CrossRefGoogle Scholar
  25. 25.
    Reincke M, Sbiera S, Hayakawa A et al (2015) Mutations in the deubiquitinase gene USP8 cause Cushing’s disease. Nat Genet 47:31–38.  https://doi.org/10.1038/ng.3166 CrossRefGoogle Scholar
  26. 26.
    Ma ZY, Song ZJ, Chen JH et al (2015) Recurrent gain-of-function USP8 mutations in Cushing’s disease. Cell Res 25(3):306–317CrossRefGoogle Scholar
  27. 27.
    Perez-Rivas L, Theodoropoulou M, Ferraù F et al (2015) The gene of the ubiquitin-specific protease 8 is frequently mutated in adenomas causing Cushing’s disease. J Clin Endocrinol Metab 100:E997–E1004.  https://doi.org/10.1210/jc.2015-1453 CrossRefGoogle Scholar
  28. 28.
    Albani A, Pérez-Rivas L, Dimopoulou C et al (2018) The USP8 mutational status may predict long-term remission in patients with Cushing’s disease. Clin Endocrinol.  https://doi.org/10.1111/cen.13802 Google Scholar
  29. 29.
    Marova E, Kolesnikova G, Arapova S et al (2016) Factors predicting the outcomes of removal of corticotropinom in Cushing’s disease. Endocr Surg 10(4):20–30.  https://doi.org/10.14341/serg2016420-30 (in Russian)CrossRefGoogle Scholar
  30. 30.
    Galiana P, Montañana C, Riesgo Suárez P et al (2013) Predictors of long-term remission after transsphenoidal surgery in Cushing’s disease. Endocrinol Nutr 60(8):475–482.  https://doi.org/10.1016/j.endonu.2012.09.009 CrossRefGoogle Scholar
  31. 31.
    Bansal P, Lila A, Goroshi M et al (2017) Duration of post-operative hypocortisolism predicts sustained remission after pituitary surgery for Cushing’s disease. Endocr Connect 6(8):625–636.  https://doi.org/10.1530/EC-17-0175 CrossRefGoogle Scholar
  32. 32.
    Johnston P, Kennedy L, Hamrahian A et al (2017) Surgical outcomes in patients with Cushing’s disease: the Cleveland Clinic experience. Pituitary.  https://doi.org/10.1007/s11102-017-0802-127 Google Scholar
  33. 33.
    Lambert J, Goldberg L, Fayngold S et al (2013) Predictors of mortality and long-term outcomes in treated Cushing’s disease: a study of 346 patients. J Clin Endocrinol Metab 98(3):1022–1030.  https://doi.org/10.1210/jc.2012-2893 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Endocrinology Research CentreMoscowRussia
  2. 2.National Research University Higher School of EconomicsMoscowRussia
  3. 3.Pirogov Russian National Research Medical UniversityMoscowRussia

Personalised recommendations