Predictive factors for recurrence of Cushing’s disease after pituitary surgery

##plugins.themes.academic_pro.article.main##

Meriem Yazidi
Ibtissem Oueslati
Nadia Khessairi
Fatma Chaker
Melika Chihaoui

Abstract

Introduction: The first-line treatment for Cushing`s disease (CD) is transsphenoidal excision of the corticotropic adenoma.

Aim: To identify the predictive factors of recurrence of corticotropic adenomas after pituitary surgery.

Methods: This is a retrospective and longitudinal study conducted in 28 patients operated for corticotropic adenoma between 1987 and
2014 and followed up in the department of endocrinology of La Rabta Hospital in Tunis (Tunisia). The mean duration of follow-up was 82 ±
65.9 months. The population was subdivided into two groups according to the occurrence or not of a recurrence. Recurrence was defined by
hormonally confirmed postoperative recurrence of Cushing`s syndrome.

Results: The mean age of the patients was 30.8±11.8 years (24 women and 4 men). CD was related to a microadenoma in 46% of cases
(n=13) and a macroadenoma in 54% of cases (n=15). The recurrence rate was 28% (n=8/28). The mean time to diagnosis of recurrence was
5.6±4 years. The sex ratio (F/M) was 7 in the recurrence group (R) and 5.6 in the non-recurrence group (NR); p= NS. The mean age of patients
in the (R) group was 27.2±11.8 years and 32.2±11.9 years in the (NR) group; p= NS. The recurrence rate was 63% in case of macroadenoma
and 37% in case of microadenoma; p= NS. Postoperative cortisolemia was significantly higher in the recurrence group (23.2 ± 13.5 µg/dl vs
4.4 ± 3.9 µg/dl; p<0.001). A postoperative cortisol level > 4.4 µg/dl was significantly associated with recurrence (100% vs 26.3%; p= 0.001).
The duration of corticotropic axis inertia was 67.2 ± 47.7 months in the (R) group versus 88.37 ± 72.14 months in the (NR) group; p= NS.

Conclusions: Nearly a quarter of patients operated for CD develop a recurrence within five years. A postoperative cortisol level > 4.4 µg/dl is
predictive of disease recurrence. Multicenter studies and a larger sample are needed to support these results.

Keywords:

Cushing’s disease – Pituitary adenoma – Pituitary surgery - Recurrence

##plugins.themes.academic_pro.article.details##

References

  1. Steffensen C, Bak AM, Rubeck KZ & Jørgensen JO. Epidemiology of Cushing’s syndrome. Neuroendocrinology 2010; 92 (Suppl 1): 1–5.
  2. Indholm J, Juul S, Jørgensen JO, Astrup J, Bjerre P, FeldtRasmussen U, Hagen C, Jørgensen J, Kosteljanetz M, Kristensen Let al. Incidence and late prognosis of Cushing’s syndrome: a population-based study. Journal of Clinical Endocrinology and Metabolism 2001; 86: 117–123.
  3. Arnardo ́ttir S & Sigurjonsdo ́ttir HA. The incidence and prevalence of Cushing’s disease may be higher than previously thought: results from a retrospective study in Iceland 1955 through 2009. Clinical Endocrinology 2011; 74: 792–793.
  4. R.N.Clayton .Mortality in Cushing’s Disease. Neuroendocrinology 2010; 92(suppl 1):71–76.
  5. Leah T. Braun, German Rubinstein, Stephanie Zopp, Frederick Vogel, Christine Schmid-Tannwald, Montserrat Pazos Escudero et al. Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment. Endocrine 2020; 70:218–231.
  6. Shimon I, Ram Z, Cohen ZR, Hadani M. Transsphenoidal surgery for Cushing’s disease: endocrinological follow-up monitoring of 82 patients. Neurosurgery 2002; 51(1):57–61.
  7. Krystallenia I, Alexandraki, Gregory A Kaltsas, Andrea M Isidori, Helen L Storr, Farhad Afshar, Ian Sabin et al. Longterm remission and recurrence rates in Cushing’s disease: predictive factors in a single-centre study. European Journal of Endocrinology 2013; 168 :639–648
  8. Toms GC, McCarthy MI, Niven MJ, Orteu CH, King TT & Monson JP. Predicting relapse after transsphenoidal surgery for Cushing’s disease. Journal of Clinical Endocrinology and Metabolism 1993; 76: 291–294.
  9. S. Petersenn, A. Beckers, D. Ferone, A. van der Lely, J. Bollerslev, M. Boscaro et al. 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 2015; 172(6): 227–239.
  10. D. Bochicchio, M. Losa, M. Buchfelder. 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. 1995; 80 (11): 3114–3120.
  11. M. Fleseriu, A.H. Hamrahian, A.R. Hoffman, D.F. Kelly, L.Katznelson, American association of clinical endocrinologists and American college of endocrinology disease state clinical review: diagnosis of recurrence in Cushing disease. Endocr.Pract. 2016; 22(12): 1436–1448.
  12. J.R. Lindsay, E.H. Oldfield, C.A. Stratakis, L.K. Nieman, The postoperative basal cortisol and CRH tests for prediction of longterm remission from Cushing’s disease after transsphenoidal surgery. J. Clin. Endocrinol. Metab. 2011; 96(7): 2057–2064.
  13. N. Ironside, G. Chatain, D. Asuzu, S. Benzo, M. Lodish, S. Sharma, L. Nieman, C.A. Stratakis, R.R. Lonser, P. Chittiboina. Earlier post-operative hypocortisolemia may predict durable remission from Cushing’s disease. Eur. J. Endocrinol. 2018; 178 (3): 255–263.
  14. M. Mayberg, S. Reintjes, A. Patel, K. Moloney, J. Mercado, A. Carlson, J. Scanlan, F. Broyles, Dynamics of postoperative serum cortisol after transsphenoidal surgery for Cushing’s disease: implications for immediate reoperation and remission. J. Neurosurg. 2018; 129(5): 1268–1277.
  15. Y. Liu, X. Liu, X. Hong, P. Liu, X. Bao, Y. Yao, B. Xing, Y. Li, Y. Huang, H. Zhu, L. Lu, R. Wang, M. Feng. Prediction of recurrence after transsphenoidal surgery for cushing’s disease: the use of machine learning algorithms. Neuroendocrinology 2019; 108 (3): 201–210.
  16. J. Ramm-Pettersen, H. Halvorsen, J.A. Evang, P. Rønning, P.K. Hol, J. Bollerslev, J. Berg-Johnsen, E. Helseth. 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. 2015; 15: 62.
  17. L.B. Yap, H.E. Turner, C.B. Adams, J.A. Wass. Undetectable postoperative cortisol does not always predict long-term remission in Cushing’s disease: a single centre audit. Clin. Endocrinol. 2002; 56(1): 25–31.
  18. A.M. Pereira, M.O. van Aken, H. van Dulken, P.J. Schutte, N.R. Biermasz, J.W. Smit, F. Roelfsema, J.A. Romijn. Long-term predictive value of postsurgical cortisol concentrations for cure and risk of recurrence in Cushing’s disease. J. Clin. Endocrinol. Metab. 2003 ; 88(12): 5858–5864.
  19. C. Brichard, E. Costa, E. Fomekong, D. Maiter, C. Raftopoulos, Outcome of transsphenoidal surgery for cushing disease: a single-center experience over 20 Years. World Neurosurg 2018; 119 : e106–e117
  20. A.M. Abu Dabrh, N.M. Singh Ospina, A. Al Nofal, W.H. Farah, P. Barrionuevo, M. Sarigianni, et al. Predictors of biochemical remission and recurrence after surgical and radiation treatments of Cushing disease: a systematic review and meta-analysis. Endocr. Pract 2016 ; 22 (4) : 466–475.
  21. C.-H. Kuo, S.-R. Shih, H.-Y. Li, S.-C. Chen, P.-J. Hung, F.-Y. Tseng, T.-C. Chang. Adrenocorticotropic hormone levels before treatment predict recurrence of Cushing’s disease. J. Formos Med. Assoc. 2017 ; 116(6) : 441–447.
  22. Langlois, F.; Lim, D.S.T.; Yedinak, C.G.; Cetas, I.; McCartney, S.; Cetas, J.; Dogan, A.; Fleseriu, M. Predictors of silent corticotroph adenoma recurrence; a large retrospective single center study and systematic literature review. Pituitary 2017 ; 21 : 32–40.
  23. Prognostic Factors for Recurrence in Pituitary Adenomas: Recent Progress and Future Directions. Diagnostic