Skip to main content
SpringerLink
Log in

Prevalence of double pituitary adenomas in a surgical series: Clinical, histological and genetic features

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background: The term double pituitary adenomas (DPA) is usually referred to those rare lesions showing two distinct cellular components. Genetic background may sustain the proliferation of more than one cell at the same time but no information is available on the presence of aip mutations in these patients. Aim: We report the prevalence and the endocrinological, neuroradiological, histopathological and genetic features of DPA detected in a large surgical series. The contribution of pituitary transcription factor immunostains in DPA was also evaluated. Subjects and methods: One-hundred-forty-four patients undergoing surgery for tumors of the sellar region were evaluated. Histopathology, immunohistochemistry and the mutational analysis for the entire coding region of the AIP and MEN1 genes were performed. Results: One-hundred-seventeen patients out of 144 had a pituitary adenoma. DPA was found in 3 (2.6%) out of 117 patients with pituitary adenoma. Immunohistochemistry and transcription factors analysis demonstrated two not yet described histotype associations in DPA. The coexistence of somatotroph-lactotroph and silent mammosomatotroph histotype in 1 case and the coexistence of sparsely granulated lactotroph and null cell adenomas in the remaining two cases were first identified. Sequencing data for the coding region of the aip and the menin gene resulted in wild type sequences in all patients with DPA. Conclusions: The prevalence of DPA observed in our unselected surgical series is not negligible (2.6%). Furthermore, the evaluation of the treatment outcome would suggest that the clinical management of DPAs requires a careful diagnostic approach and follow-up.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ezzat S, Asa SL, Couldwell WT, et al. The prevalence of pituitary adenomas: a systematic review. Cancer 2004, 101: 613–9.

    Article  PubMed  Google Scholar 

  2. Davis JR, Farrell WE, Clayton RN. Pituitary tumours. Reproduction 2001, 121: 363–71.

    Article  PubMed  CAS  Google Scholar 

  3. Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 2006, 91: 4769–75.

    Article  PubMed  CAS  Google Scholar 

  4. Asa S. Pratical Pituitary Pathology. What does the pathologist need to know? Arch Pathol Lab Med 2008, 132: 1231–40.

    PubMed  Google Scholar 

  5. Kontogeorgos G, Kovacs K, Horvath E, Scheithauer BW. Multiple adenomas of the human pituitary. A retrospective autopsy study with clinical implications. J Neurosurg 1991, 74: 243–7.

    Article  PubMed  CAS  Google Scholar 

  6. Asa SL, Ezzat S. The cytogenesis and pathogenesis of pituitary adenomas. Endocr Rev 1988, 19: 798–827.

    Google Scholar 

  7. Osamura RY, Kajiya H, Takei M, et al. Pathology of the human pituitary adenomas. Histochem Cell Biol 2008, 130: 495–507.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Kim K, Yamada S, Usui M, Sano T. Preoperative identification of clearly separated double pituitary adenomas. Clin Endocrinol 2004, 61: 26–30.

    Article  Google Scholar 

  9. Syro LV, Horvath E, Kovacs K. Double adenoma of the pituitary: a somatotroph adenoma colliding with a gonadotroph adenoma. J Endocrinol Invest 2000, 23: 37–41.

    Article  PubMed  CAS  Google Scholar 

  10. Sano T, Horiguchi H, Xu B, et al. Double pituitary adenomas: six surgical cases. Pituitary 1999, 1: 243–50.

    Article  PubMed  CAS  Google Scholar 

  11. Kannuki S, Matsumoto K, Sano T, Shintani Y, Bando H, Saito S. Double pituitary adenoma-two case reports. Neurol Med Chir (Tokyo) 1996, 36: 818–21.

    Article  CAS  Google Scholar 

  12. Kontogeorgos G, Scheithauer BW, Horvath E, et al. Double adenomas of the pituitary: a clinicopathological study of 11 tumors. Neurosurgery 1992, 31: 840–9.

    Article  PubMed  CAS  Google Scholar 

  13. Meij BP, Lopes MB, Vance ML, Thorner MO, Laws ER Jr. Double pituitary lesions in three patients with Cushing’s disease. Pituitary 2000, 3: 159–68.

    Article  PubMed  CAS  Google Scholar 

  14. Ratliff JK, Oldfield EH. Multiple pituitary adenomas in Cushing’s disease. J Neurosurg 2000, 93: 753–61.

    Article  PubMed  CAS  Google Scholar 

  15. Tomita T, Gates E. Pituitary adenomas and granular cell tumors. Incidence, cell type, and location of tumor in 100 pituitary glands at autopsy. Am J Clin Pathol 1999, 111: 817–25.

    PubMed  CAS  Google Scholar 

  16. Tomita T, Kuziez M, Watanabe I. Double tumors of anterior and posterior pituitary gland. Acta Neuropathol 1981, 54: 161–4.

    Article  PubMed  CAS  Google Scholar 

  17. Tolis G, Bertrand G, Carpenter S, McKenzie JM. Acromegaly and galactorrhea-amenorrhea with two pituitary adenomas secreting growth hormone or prolactin. A case report. Ann Intern Med 1978, 89: 345–58.

    CAS  Google Scholar 

  18. McKelvie PA, McNeill P. Double pituitary adenomas: a series of three patients. Pathology 2002, 34: 57–60.

    Article  PubMed  Google Scholar 

  19. Shimizu C, Koike T, Sawamura Y. Double pituitary adenomas with distinct histological features and immunophenotypes. J Neurol Neurosurg Psychiatry 2004, 75: 140.

    PubMed Central  PubMed  CAS  Google Scholar 

  20. Jastania RA, Alsaad KO, Al-Shraim M, Kovacs K, Asa SL. Double adenomas of the pituitary: transcription factors Pit-1, T-pit, and SF-1 identify cytogenesis and differentiation. Endocr Pathol 2005, 16: 187–94.

    Article  PubMed  CAS  Google Scholar 

  21. Daly AF, Jaffrain-Rea ML, Beckers A. Clinical and genetic features of familial pituitary adenomas. Horm Metab Res 2005, 37: 347–54.

    Article  PubMed  CAS  Google Scholar 

  22. Daly AF, Jaffrain-Rea ML, Ciccarelli A, et al. Clinical characterization of familial isolated pituitary adenomas. J Clin Endocrinol Metab 2006, 91: 3316–23.

    Article  PubMed  CAS  Google Scholar 

  23. Al Brahim NY, Rambaldini G, Ezzat S, Asa SL. Complex endocrinopathies in MEN-diagnostic dilemmas in endocrine oncology. Endocrine Pathol 2007, 18: 37–41.

    Article  Google Scholar 

  24. Trouillas J, Labat-Moleur F, Sturm N, et al. A case-control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol 2008, 32: 534–43.

    Article  PubMed  Google Scholar 

  25. Vierimaa O, Georgitsi M, Lehtonen R, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 2006, 312: 1228–30.

    Article  PubMed  CAS  Google Scholar 

  26. Gadelha MR, Prezant TR, Une KN, et al. Loss of heterozygosity on chromosome 11q13 in two families with acromegaly/gigantism is independent of mutations of the multiple endocrine neoplasia type I gene. J Clin Endocrinol Metab 1999, 84: 249–56.

    PubMed  CAS  Google Scholar 

  27. Cazabat L, Libè R, Perlemoine K, et al. Germline inactivating mutations of the aryl hydrocarbon receptor-interacting protein gene in a large cohort of sporadic acromegaly: mutations are found in a subset of young patients with macroadenomas. Eur J Endocrinol 2007, 157: 1–8.

    Article  PubMed  CAS  Google Scholar 

  28. Georgitsi M, Raitila A, Karhu A, et al. Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations. Proc Natl Acad Sci USA 2007, 104: 4101–5.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Toledo RA, Lourenco DM Jr, Liberman B, et al. Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma. J Clin Endocrinol Metab 2007, 92: 1934–7.

    Article  PubMed  CAS  Google Scholar 

  30. Barlier A, Vanbellinghen JF, Daly AF, et al. Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas. J Clin Endocrinol Metab 2007, 92: 1952–5.

    Article  PubMed  CAS  Google Scholar 

  31. Daly AF, Vanbellinghen JF, Khoo SK, et al. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab 2007, 92: 1891–6.

    Article  PubMed  CAS  Google Scholar 

  32. Villa C, Magri F, Morbini P, et al. Silent familial isolated pituitary adenomas: histopathological and clinical case report. Endocr Pathol 2008, 19: 40–6.

    Article  PubMed  CAS  Google Scholar 

  33. DeLellis R, Lloyd RV, Heitz PU, Eng C. WHO Classification of tumours. Pathology & genetics. Tumours of Endocrine Organs. 2004.

  34. Al-Brahim NY, Asa SL. My approach to pathology of the pituitary gland. J Clin Pathol 2006, 59: 1245–53.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  35. Johnsen DE, Woodruff WW, Allen IS, Cera PJ, Funkhouser GR, Coleman LL. MR imaging of the sellar and juxtasellar regions. Radiographics 1991, 11: 727–58.

    Article  PubMed  CAS  Google Scholar 

  36. Asa SL, Kovacs K, Singer W. Human fetal adenohypophysis: morphologic and functional analysis in vitro. Neuroendocrinology 1991, 53: 562–72.

    Article  PubMed  CAS  Google Scholar 

  37. Gadelha MR, Une KN, Rohde K, Vaisman M, Kineman RD, Frohman LA. Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1–11q13.3 and evidence for a potential second locus at chromosome 2p16-12. J Clin Endocrinol Metab 2000, 85: 707–14.

    PubMed  CAS  Google Scholar 

  38. Leontiou CA, Gueorguiev M, van der Spuy J, et al. The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. J Clin Endocrinol Metab 2008, 93: 2390–401.

    Article  PubMed  CAS  Google Scholar 

  39. Arafat AM, Mohlig M, Weickert MO, et al. Growth hormone response during oral glucose tolerance test: the impact of assay method on the estimation of reference values in patients with acromegaly and in healthy controls, and the role of gender, age, and body mass index. J Clin Endocrinol Metab 2008, 93: 1254–62.

    Article  PubMed  CAS  Google Scholar 

  40. Alexopoulou O, Bex M, Abs R, T’sjoen G, Velkeniers B, Maiter D. Divergence between growth hormone and insulin-like growth factor-I concentrations in the follow up of acromegaly. J Clin Endocrinol Metab 2008, 93: 1324–30.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri IRCCS, Istituto Superiore Prevenzione e Sicurezza Lavoro, Laboratory for Endocrine Disruptors, Chair of Endocrinology and Metabolic Diseases, University of Pavia, Pavia, Italy

    F. Magri, M. S. Lagonigro, E. Gabellieri, M. Rotondi & L. Chiovato MD, PhD

  2. Department of Human and Hereditary Pathology, Pathology Section, Fondazione S. Matteo IRCCS, Pavia, Italy

    C. Villa, P. Morbini & E. Solcia

  3. Neurosurgery Unit, Fondazione S. Matteo IRCCS, Pavia, Italy

    D. Locatelli

  4. Neuroradiology Unit, Fondazione S. Matteo IRCCS, Pavia, Italy

    P. Scagnelli

  5. Department of Medical and Surgical Sciences, Internal Medicine and Endocrinology Unit, University of Brescia, Brescia, Italy

    M. Castellano

  6. Department of Endocrinology, Centre Hospitalier Universitaire Liège, University of Liège, Liège, Belgium

    A. F. Daly

Authors
  1. F. Magri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Villa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Locatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Scagnelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. S. Lagonigro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Morbini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Castellano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. Gabellieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. Rotondi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. E. Solcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A. F. Daly
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. L. Chiovato MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Chiovato MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magri, F., Villa, C., Locatelli, D. et al. Prevalence of double pituitary adenomas in a surgical series: Clinical, histological and genetic features. J Endocrinol Invest 33, 325–331 (2010). https://doi.org/10.1007/BF03346594

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03346594

Keywords

Search

Navigation