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Current status on histological classification in Cushing’s disease

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Abstract

Introduction

Managing Cushing’s disease remains a challenge. Surgery is the first option of treatment and it offers a high success rate. Even in cases where biochemical remission is not achieved, it is crucial to obtain surgical tissue for morphological diagnosis because the therapeutic approach can be modified according to the findings.

Materials and Methods

A literature search was performed using PubMed for information regarding pathology and Cushing’s disease.

Results

The histopathological features found in the pituitary gland of patients with Cushing’s disease are presented.

Conclusion

Different subtypes of ACTH-producing pituitary tumors are recognized and characterized. The significance of finding a normal pituitary gland with or without Crooke’s changes is also discussed.

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References

  1. Cushing H (1932) The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). Bull Johns Hopkins Hosp 50:137–195

    Google Scholar 

  2. Bertagna X, Guignat L (2013) Approach to the Cushing’s disease patient with persistent/recurrent hypercortisolism after pituitary surgery. J Clin Endocrinol Metab 98(4):1307–1318. doi:10.1210/jc.2012-3200

    Article  CAS  PubMed  Google Scholar 

  3. Gadelha MR, Vieira Neto L (2014) Efficacy of medical treatment in Cushing’s disease: a systematic review. Clin Endocrinol 80(1):1–12. doi:10.1111/cen.12345

    Article  CAS  Google Scholar 

  4. Fleseriu M, Petersenn S (2013) New avenues in the medical treatment of Cushing’s disease: corticotroph tumor targeted therapy. J Neurooncol 114(1):1–11. doi:10.1007/s11060-013-1151-1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Feelders RA, Hofland LJ (2013) Medical treatment of Cushing’s disease. J Clin Endocrinol Metab 98(2):425–438. doi:10.1210/jc.2012-3126

    Article  CAS  PubMed  Google Scholar 

  6. Fleseriu M, Petersenn S (2012) Medical management of Cushing’s disease: what is the future? Pituitary 15(3):330–341. doi:10.1007/s11102-012-0397-5

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Cuevas-Ramos D, Fleseriu M (2014) Treatment of Cushing’s disease: a mechanistic update. J Endocrinol 223(2):R19–R39. doi:10.1530/joe-14-0300

    Article  CAS  PubMed  Google Scholar 

  8. Nieman LK (2013) Update in the medical therapy of Cushing’s disease. Curr Opin Endocrinol Diabetes Obes 20(4):330–334. doi:10.1097/MED.0b013e3283631809

    PubMed Central  CAS  PubMed  Google Scholar 

  9. Mete O, Asa SL (2013) Therapeutic implications of accurate classification of pituitary adenomas. Semin Diagn Pathol 30(3):158–164. doi:10.1053/j.semdp.2013.06.002

    Article  PubMed  Google Scholar 

  10. Mete O, Asa SL (2012) Clinicopathological correlations in pituitary adenomas. Brain Pathol 22(4):443–453. doi:10.1111/j.1750-3639.2012.00599.x

    Article  PubMed  Google Scholar 

  11. Asa SL (2011) Tumors of the pituitary Gland, vol. Fascicle 15, 4th Series. The Atlas of Tumor Pathology. Armed Forces Institute of Pathology, Washington, DC

  12. Osamura RY, Kajiya H, Takei M, Egashira N, Tobita M, Takekoshi S, Teramoto A (2008) Pathology of the human pituitary adenomas. Histochem Cell Biol 130(3):495–507. doi:10.1007/s00418-008-0472-1

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Syro LV, Builes CE, Di Ieva A, Sav A, Rotondo F, Kovacs K (2014) Improving differential diagnosis of pituitary adenomas. Expert Rev Endocrinol Metab 9(4):377–386. doi:10.1586/17446651.2014.922412

    Article  CAS  Google Scholar 

  14. Cuevas-Ramos D, Fleseriu M (2014) Somatostatin receptor ligands and resistance to treatment in pituitary adenomas. J Mol Endocrinol 52(3):R223–R240. doi:10.1530/jme-14-0011

    Article  CAS  PubMed  Google Scholar 

  15. Chinezu L, Vasiljevic A, Jouanneau E, Francois P, Borda A, Trouillas J, Raverot G (2014) Expression of somatostatin receptors, SSTR2A and SSTR5, in 108 endocrine pituitary tumors using immunohistochemical detection with new specific monoclonal antibodies. Hum Pathol 45(1):71–77. doi:10.1016/j.humpath.2013.08.007

    Article  CAS  PubMed  Google Scholar 

  16. Mete O, Ezzat S, Asa SL (2012) Biomarkers of aggressive pituitary adenomas. J Mol Endocrinol 49(2):R69–R78. doi:10.1530/jme-12-0113

    Article  CAS  PubMed  Google Scholar 

  17. Sav A, Rotondo F, Syro LV, Scheithauer BW, Kovacs K (2012) Biomarkers of pituitary neoplasms. Anticancer Res 32(11):4639–4654

    CAS  PubMed  Google Scholar 

  18. Takeshita A, Inoshita N, Taguchi M, Okuda C, Fukuhara N, Oyama K, Ohashi K, Sano T, Takeuchi Y, Yamada S (2009) High incidence of low O(6)-methylguanine DNA methyltransferase expression in invasive macroadenomas of Cushing’s disease. Eur J Endocrinol 161(4):553–559. doi:10.1530/EJE-09-0414

    Article  CAS  PubMed  Google Scholar 

  19. Salehi F, Scheithauer BW, Kovacs K, Horvath E, Syro LV, Sharma S, Manoranjan B, Cusimano M (2012) O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemical expression in pituitary corticotroph adenomas. Neurosurgery 70(2):491–496. doi:10.1227/NEU.0b013e318230ac63; discussion 496

    Article  PubMed  Google Scholar 

  20. McCormack A, Kaplan W, Gill AJ, Little N, Cook R, Robinson B, Clifton-Bligh R (2013) MGMT expression and pituitary tumours: relationship to tumour biology. Pituitary 16(2):208–219. doi:10.1007/s11102-012-0406-8

    Article  CAS  PubMed  Google Scholar 

  21. Bode H, Seiz M, Lammert A, Brockmann MA, Back W, Hammes HP, Thome C (2010) SOM230 (pasireotide) and temozolomide achieve sustained control of tumour progression and ACTH secretion in pituitary carcinoma with widespread metastases. Exp Clin Endocrinol Diabetes 118(10):760–763. doi:10.1055/s-0030-1253419

    Article  CAS  PubMed  Google Scholar 

  22. Thearle MS, Freda PU, Bruce JN, Isaacson SR, Lee Y, Fine RL (2011) Temozolomide (Temodar®) and capecitabine (Xeloda®) treatment of an aggressive corticotroph pituitary tumor. Pituitary 14(4):418–424. doi:10.1007/s11102-009-0211-1

    Article  PubMed Central  PubMed  Google Scholar 

  23. Zacharia BE, Gulati AP, Bruce JN, Carminucci AS, Wardlaw SL, Siegelin M, Remotti H, Lignelli A, Fine RL (2014) High response rates and prolonged survival in patients with corticotroph pituitary tumors and refractory Cushing disease from capecitabine and temozolomide (CAPTEM): a case series. Neurosurgery 74(4):E447–E455. doi:10.1227/neu.0000000000000251; discussion E455

    Article  PubMed  Google Scholar 

  24. Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C, Viennet G, Bonneville JF, Assaker R, Auger C, Brue T, Cornelius A, Dufour H, Jouanneau E, Francois P, Galland F, Mougel F, Chapuis F, Villeneuve L, Maurage CA, Figarella-Branger D, Raverot G, Barlier A, Bernier M, Bonnet F, Borson-Chazot F, Brassier G, Caulet-Maugendre S, Chabre O, Chanson P, Cottier JF, Delemer B, Delgrange E, Di Tommaso L, Eimer S, Gaillard S, Jan M, Girard JJ, Lapras V, Loiseau H, Passagia JG, Patey M, Penfornis A, Poirier JY, Perrin G, Tabarin A (2013) A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol 126(1):123–135. doi:10.1007/s00401-013-1084-y

    Article  PubMed  Google Scholar 

  25. Raverot G, Jouanneau E, Trouillas J (2014) Clinicopathological classification and molecular markers of pituitary tumours for personalized therapeutic strategies. Eur J Endocrinol. doi:10.1530/eje-13-1031

    Google Scholar 

  26. Di Ieva A, Rotondo F, Syro LV, Cusimano MD, Kovacs K (2014) Aggressive pituitary adenomas–diagnosis and emerging treatments. Nat Rev Endocrinol 10(7):423–435. doi:10.1038/nrendo.2014.64

    PubMed  Google Scholar 

  27. Crooke AC (1935) A change in the basophil cells of the pituitary gland common to conditions which exhibit the syndrome attributed to basophil adenoma. J Pathol Bacteriol 41:339–349

    Article  Google Scholar 

  28. George DH, Scheithauer BW, Kovacs K, Horvath E, Young WF Jr, Lloyd RV, Meyer FB (2003) Crooke’s cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. Am J Surg Pathol 27(10):1330–1336

    Article  PubMed  Google Scholar 

  29. Holthouse DJ, Robbins PD, Kahler R, Knuckey N, Pullan P (2001) Corticotroph pituitary carcinoma: case report and literature review. Endocr Pathol 12(3):329–341

    Article  CAS  PubMed  Google Scholar 

  30. Heaney AP (2011) Pituitary carcinoma: difficult diagnosis and treatment. J Clin Endocrinol Metab 96(12):3649–3660. doi:10.1210/jc.2011-2031

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Thynne T, White GH, Burt MG (2014) Factitious Cushing’s syndrome masquerading as Cushing’s disease. Clin Endocrinol 80(3):328–332. doi:10.1111/cen.12343

    Article  CAS  Google Scholar 

  32. Romanholi DJ, Salgado LR (2007) Pseudo-Cushing states. Arquivos brasileiros de endocrinologia e metabologia 51(8):1303–1313

    Article  PubMed  Google Scholar 

  33. Shahani S, Nudelman R, Nalini R, Kim H-S, Samson S (2010) Ectopic corticotropin-releasing hormone (CRH) syndrome from metastatic small cell carcinoma: a case report and review of the literature. Diagn Pathol 5(1):56

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Authors are grateful to the Jarislowsky and Lloyd Carr-Harris Foundations for their generous support.

Conflict of interest

The authors wish to declare that they have no conflict of interest and they have not received any financial compensation for this work.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Hospital Pablo Tobon Uribe, Clinica Medellin and Group of Genetics, Regeneration and Cancer, Universidad de Antioquia, Medellín, Colombia

    Luis V. Syro

  2. Laboratory Medicine, Division of Pathology, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

    Fabio Rotondo, Eva Horvath & Kalman Kovacs

  3. Division of Neurosurgery, Department of Surgery, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

    Michael D. Cusimano & Antonio Di Ieva

  4. Division of Endocrinology, Clinica Medellin, Medellín, Colombia

    Lina M. Restrepo

  5. Division of Endocrinology, Etobicoke Endocrine Clinic, Toronto, Canada

    Min Wong

  6. Department of Endocrinology, Western University, London, ON, Canada

    Donald W. Killinger

  7. Department of Neurosurgery, Trillium Health Centre, Mississauga, ON, Canada

    Harley Smyth

Authors
  1. Luis V. Syro
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  2. Fabio Rotondo
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  3. Michael D. Cusimano
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  4. Antonio Di Ieva
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  5. Eva Horvath
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  6. Lina M. Restrepo
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  7. Min Wong
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  8. Donald W. Killinger
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  9. Harley Smyth
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  10. Kalman Kovacs
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Corresponding author

Correspondence to Luis V. Syro.

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Syro, L.V., Rotondo, F., Cusimano, M.D. et al. Current status on histological classification in Cushing’s disease. Pituitary 18, 217–224 (2015). https://doi.org/10.1007/s11102-014-0619-0

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  • DOI: https://doi.org/10.1007/s11102-014-0619-0

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