, Volume 12, Issue 1, pp 15–22 | Cite as

Radiotherapy of nonfunctioning and gonadotroph adenomas

  • Andrew A. Kanner
  • Benjamin W. Corn
  • Yona GreenmanEmail author


Transsphenoidal surgery is the treatment of choice for NFPA but is seldom curative. The management of patients in whom residual tumor is detected after surgery is not clear-cut. Radiation therapy is effective in controlling tumor mass in the majority of patients, but is associated with long term complications that call for restriction of its use to patients at high risk for tumor growth. New radiation techniques may prove to be safer while retaining the effectiveness of conventional radiotherapy, however longer follow-up is necessary to confirm this assumption. For now, it appears to be safe to withhold radiation and carefully follow patients with small tumor remnants, whereas large remnants from invasive tumors should be considered for radiotherapy. Nevertheless, there are no prospective controlled studies that support this empirical approach.


Pituitary adenoma Non-secreting Conventional radiotherapy Conformal radiotherapy Stereotactic radiosurgery 



The authors want to thank Prof. Deborah T. Blumenthal M.D. for the critical review of the manuscript.


  1. 1.
    Saeger W et al (2007) Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol 156(2):203–216PubMedCrossRefGoogle Scholar
  2. 2.
    Al-Shraim M, Asa SL (2006) The 2004 World Health Organization classification of pituitary tumors: What is new? Acta Neuropathol 111(1):1–7PubMedCrossRefGoogle Scholar
  3. 3.
    Yamada S et al (2007) A study of the correlation between morphological findings and biological activities in clinically nonfunctioning pituitary adenomas. Neurosurgery 61(3):580–584; discussion 584–585PubMedGoogle Scholar
  4. 4.
    Breen P et al (1998) Radiotherapy for nonfunctional pituitary adenoma: analysis of long-term tumor control. J Neurosurg 89(6):933–938PubMedGoogle Scholar
  5. 5.
    Greenman Y, Melmed S (1996) Diagnosis and management of nonfunctioning pituitary tumors. Annu Rev Med 47:95–106PubMedCrossRefGoogle Scholar
  6. 6.
    Mastronardi L, Guiducci A (2002) Are nonfunctioning pituitary adenomas extending into the cavernous sinus aggressive and/or invasive? Neurosurgery 51(2):521–522; author reply 522PubMedCrossRefGoogle Scholar
  7. 7.
    Vance ML (1997) Nonfunctioning pituitary adenoma. Curr Ther Endocrinol Metab 6:33–35PubMedGoogle Scholar
  8. 8.
    Ciric I et al (1983) Transsphenoidal microsurgery of pituitary macroadenomas with long-term follow-up results. J Neurosurg 59(3):395–401PubMedGoogle Scholar
  9. 9.
    Black PM, Zervas NT, Candia G (1988) Management of large pituitary adenomas by transsphenoidal surgery. Surg Neurol 29(6):443–447PubMedCrossRefGoogle Scholar
  10. 10.
    Ferrante E et al (2006) Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. Eur J Endocrinol 155(6):823–829PubMedCrossRefGoogle Scholar
  11. 11.
    Honegger J et al (2007) Objective criteria for successful transsphenoidal removal of suprasellar nonfunctioning pituitary adenomas. A prospective study. Acta Neurochir (Wien) 149(1):21–29; discussion 29CrossRefGoogle Scholar
  12. 12.
    Zhang X et al (1999) Management of nonfunctioning pituitary adenomas with suprasellar extensions by transsphenoidal microsurgery. Surg Neurol 52(4):380–385PubMedCrossRefGoogle Scholar
  13. 13.
    Kanner AA et al (2002) Intracranial navigation by using low-field intraoperative magnetic resonance imaging: preliminary experience. J Neurosurg 97(5):1115–1124PubMedGoogle Scholar
  14. 14.
    Brada M et al (1993) The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas. Clin Endocrinol (Oxf) 38(6):571–578CrossRefGoogle Scholar
  15. 15.
    Bradley KM et al (1994) An audit of selected patients with non-functioning pituitary adenoma treated by transsphenoidal surgery without irradiation. Clin Endocrinol (Oxf) 41(5):655–659CrossRefGoogle Scholar
  16. 16.
    Comtois R et al (1991) The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas. Cancer 68(4):860–866PubMedCrossRefGoogle Scholar
  17. 17.
    Ebersold MJ et al (1986) Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. J Neurosurg 64(5):713–719PubMedGoogle Scholar
  18. 18.
    Arita K et al (2006) Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination. J Neurosurg 104(6):884–891PubMedCrossRefGoogle Scholar
  19. 19.
    Dekkers OM et al (2007) The natural course of non-functioning pituitary macroadenomas. Eur J Endocrinol 156(2):217–224PubMedCrossRefGoogle Scholar
  20. 20.
    Karavitaki N et al (2007) What is the natural history of nonoperated nonfunctioning pituitary adenomas? Clin Endocrinol (Oxf) 67(6):938–943CrossRefGoogle Scholar
  21. 21.
    Gittoes NJ (2003) Radiotherapy for non-functioning pituitary tumors–when and under what circumstances? Pituitary 6(2):103–108PubMedCrossRefGoogle Scholar
  22. 22.
    Dekkers OM et al (2006) Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab 91(5):1796–1801PubMedCrossRefGoogle Scholar
  23. 23.
    Park P et al (2004) The role of radiation therapy after surgical resection of nonfunctional pituitary macroadenomas. Neurosurgery 55(1):100–106; discussion 106–107PubMedCrossRefGoogle Scholar
  24. 24.
    Turner HE et al (1999) Audit of selected patients with nonfunctioning pituitary adenomas treated without irradiation - a follow-up study. Clin Endocrinol (Oxf) 51(3):281–284CrossRefGoogle Scholar
  25. 25.
    Buch HN et al (2004) Prediction of recurrence of nonfunctioning pituitary tumours by loss of heterozygosity analysis. Clin Endocrinol (Oxf) 61(1):19–25CrossRefGoogle Scholar
  26. 26.
    Dubois S et al (2007) Relevance of Ki-67 and prognostic factors for recurrence/progression of gonadotropic adenomas after first surgery. Eur J Endocrinol 157(2):141–147PubMedCrossRefGoogle Scholar
  27. 27.
    Kontogeorgos G (2006) Predictive markers of pituitary adenoma behavior. Neuroendocrinology 83(3–4):179–188PubMedCrossRefGoogle Scholar
  28. 28.
    Tanaka Y et al (2003) Growth pattern and rate in residual nonfunctioning pituitary adenomas: correlations among tumor volume doubling time, patient age, and MIB-1 index. J Neurosurg 98(2):359–365PubMedGoogle Scholar
  29. 29.
    Lillehei KO et al (1998) Reassessment of the role of radiation therapy in the treatment of endocrine-inactive pituitary macroadenomas. Neurosurgery 43(3):432–438; discussion 438–439PubMedCrossRefGoogle Scholar
  30. 30.
    Greenman Y et al (2003) Postoperative surveillance of clinically nonfunctioning pituitary macroadenomas: markers of tumour quiescence and regrowth. Clin Endocrinol (Oxf) 58(6):763–769CrossRefGoogle Scholar
  31. 31.
    Greenman Y (2007) Dopaminergic treatment of nonfunctioning pituitary adenomas. Nat Clin Pract Endocrinol Metab 3(8):554–555PubMedCrossRefGoogle Scholar
  32. 32.
    Greenman Y et al (2005) Postoperative treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists decreases tumour remnant growth. Clin Endocrinol (Oxf) 63(1):39–44CrossRefGoogle Scholar
  33. 33.
    Greenman Y et al (1998) The use of beta-subunits of gonadotrophin hormones in the follow-up of clinically non-functioning pituitary tumours. Clin Endocrinol (Oxf) 49(2):185–190CrossRefGoogle Scholar
  34. 34.
    Kremer P et al (2002) Magnetic resonance imaging after transsphenoidal surgery of clinically non-functional pituitary macroadenomas and its impact on detecting residual adenoma. Acta Neurochir (Wien) 144(5):433–443CrossRefGoogle Scholar
  35. 35.
    Wowra B, Stummer W (2002) Efficacy of gamma knife radiosurgery for nonfunctioning pituitary adenomas: a quantitative follow up with magnetic resonance imaging-based volumetric analysis. J Neurosurg 97(5 Suppl):429–432PubMedGoogle Scholar
  36. 36.
    Gittoes NJ et al (1998) Radiotherapy for non-function pituitary tumours. Clin Endocrinol (Oxf) 48(3):331–337CrossRefGoogle Scholar
  37. 37.
    Jaffrain-Rea ML et al (1993) Influence of radiotherapy on long-term relapse in clinically non-secreting pituitary adenomas. A retrospective study (1970–1988). Eur J Med 2(7):398–403PubMedGoogle Scholar
  38. 38.
    Tsang RW et al (1994) Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors. Int J Radiat Oncol Biol Phys 30(3):557–565PubMedGoogle Scholar
  39. 39.
    Woollons AC et al (2000) Non-functioning pituitary adenomas: indications for postoperative radiotherapy. Clin Endocrinol (Oxf) 53(6):713–717CrossRefGoogle Scholar
  40. 40.
    van den Bergh AC et al (2007) Immediate postoperative radiotherapy in residual nonfunctioning pituitary adenoma: beneficial effect on local control without additional negative impact on pituitary function and life expectancy. Int J Radiat Oncol Biol Phys 67(3):863–869PubMedGoogle Scholar
  41. 41.
    Tomlinson JW et al (2001) Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet 357(9254):425–431PubMedCrossRefGoogle Scholar
  42. 42.
    Mayberg M, Vermeulen S (2007) Advances in stereotactic radiosurgery in the treatment of pituitary adenomas. Curr Opin Endocrinol Diabetes Obes 14(4):296–300PubMedGoogle Scholar
  43. 43.
    Yoon SC et al (1998) Clinical results of 24 pituitary macroadenomas with linac-based stereotactic radiosurgery. Int J Radiat Oncol Biol Phys 41(4):849–853PubMedGoogle Scholar
  44. 44.
    Muramatsu J et al (2003) [Clinical results of LINAC-based stereotactic radiosurgery for pituitary adenoma]. Nippon Igaku Hoshasen Gakkai Zasshi 63(5):225–230PubMedGoogle Scholar
  45. 45.
    Leber KA, Bergloff J, Pendl G (1998) Dose-response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery. J Neurosurg 88(1):43–50PubMedGoogle Scholar
  46. 46.
    Feigl GC et al (2002) Effects of gamma knife radiosurgery of pituitary adenomas on pituitary function. J Neurosurg 97(5 Suppl):415–421PubMedGoogle Scholar
  47. 47.
    Lim YL et al (1998) Four years’ experiences in the treatment of pituitary adenomas with gamma knife radiosurgery. Stereotact Funct Neurosurg 70(Suppl 1):95–109PubMedCrossRefGoogle Scholar
  48. 48.
    Liscak R et al (2007) Gamma knife radiosurgery for endocrine-inactive pituitary adenomas. Acta Neurochir (Wien) 149(10):999–1006CrossRefGoogle Scholar
  49. 49.
    Muacevic A, Uhl E, Wowra B (2004) Gamma knife radiosurgery for nonfunctioning pituitary adenomas. Acta Neurochir Suppl 91:51–54PubMedGoogle Scholar
  50. 50.
    Petrovich Z et al (2003) Gamma knife radiosurgery for pituitary adenoma: early results. Neurosurgery 53(1):51–59; discussion 59–61PubMedCrossRefGoogle Scholar
  51. 51.
    Izawa M et al (2000) Gamma knife radiosurgery for pituitary adenomas. J Neurosurg 93(Suppl 3):19–22PubMedGoogle Scholar
  52. 52.
    Ikeda H, Jokura H, Yoshimoto T (1998) Gamma knife radiosurgery for pituitary adenomas: usefulness of combined transsphenoidal and gamma knife radiosurgery for adenomas invading the cavernous sinus. Radiat Oncol Investig 6(1):26–34PubMedCrossRefGoogle Scholar
  53. 53.
    Losa M et al (2004) Gamma knife surgery for treatment of residual nonfunctioning pituitary adenomas after surgical debulking. J Neurosurg 100(3):438–444PubMedGoogle Scholar
  54. 54.
    Mingione V et al (2006) Gamma surgery in the treatment of nonsecretory pituitary macroadenoma. J Neurosurg 104(6):876–883PubMedCrossRefGoogle Scholar
  55. 55.
    Mitsumori M et al (1998) Initial clinical results of LINAC-based stereotactic radiosurgery and stereotactic radiotherapy for pituitary adenomas. Int J Radiat Oncol Biol Phys 42(3):573–580PubMedGoogle Scholar
  56. 56.
    Voges J et al (2006) Linear accelerator radiosurgery for pituitary macroadenomas: a 7-year follow-up study. Cancer 107(6):1355–1364PubMedCrossRefGoogle Scholar
  57. 57.
    Pamir MN et al (2007) Pituitary adenomas treated with gamma knife radiosurgery: volumetric analysis of 100 cases with minimum 3 year follow-up. Neurosurgery 61(2):270–280; discussion 280PubMedCrossRefGoogle Scholar
  58. 58.
    Pan L et al (1998) Pituitary adenomas: the effect of gamma knife radiosurgery on tumor growth and endocrinopathies. Stereotact Funct Neurosurg 70(Suppl 1):119–126PubMedCrossRefGoogle Scholar
  59. 59.
    Picozzi P et al (2005) Radiosurgery and the prevention of regrowth of incompletely removed nonfunctioning pituitary adenomas. J Neurosurg 102(Suppl):71–74PubMedCrossRefGoogle Scholar
  60. 60.
    Sheehan JP et al (2003) Radiosurgery for nonfunctioning pituitary adenoma. Neurosurg Focus 14(5):e9PubMedCrossRefGoogle Scholar
  61. 61.
    Iwai Y, Yamanaka K, Yoshioka K (2005) Radiosurgery for nonfunctioning pituitary adenomas. Neurosurgery 56(4):699–705; discussion 699–705PubMedCrossRefGoogle Scholar
  62. 62.
    Pollock BE (2007) Radiosurgery for pituitary adenomas. Prog Neurol Surg 20:164–171PubMedCrossRefGoogle Scholar
  63. 63.
    Sheehan JP et al (2002) Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma. J Neurosurg 97(5 Suppl):408–414PubMedGoogle Scholar
  64. 64.
    Mokry M et al (1999) A six year experience with the postoperative radiosurgical management of pituitary adenomas. Stereotact Funct Neurosurg 72(Suppl 1):88–100PubMedCrossRefGoogle Scholar
  65. 65.
    Pollock BE, Carpenter PC (2003) Stereotactic radiosurgery as an alternative to fractionated radiotherapy for patients with recurrent or residual nonfunctioning pituitary adenomas. Neurosurgery 53(5):1086–1091; discussion 1091–1094PubMedCrossRefGoogle Scholar
  66. 66.
    Shin M et al (2000) Stereotactic radiosurgery for pituitary adenoma invading the cavernous sinus. J Neurosurg 93(Suppl 3):2–5PubMedGoogle Scholar
  67. 67.
    Laws ER et al (2004) Stereotactic radiosurgery for pituitary adenomas: a review of the literature. J Neurooncol 69(1–3):257–272PubMedCrossRefGoogle Scholar
  68. 68.
    Sheehan JP et al (2006) Stereotactic radiosurgery for pituitary adenomas: a review of the literature and our experience. Front Horm Res 34:185–205PubMedCrossRefGoogle Scholar
  69. 69.
    Sheehan JP et al (2005) Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium. J Neurosurg 102(4):678–691PubMedGoogle Scholar
  70. 70.
    Witt TC (2003) Stereotactic radiosurgery for pituitary tumors. Neurosurg Focus 14(5):e10PubMedCrossRefGoogle Scholar
  71. 71.
    Plowman PN, Doughty D (1999) Stereotactic radiosurgery, X: clinical isodosimetry of gamma knife versus linear accelerator X-knife for pituitary and acoustic tumours. Clin Oncol (R Coll Radiol) 11(5):321–329Google Scholar
  72. 72.
    Rocher FP et al (1995) Stereotactic radiosurgery: the Lyon experience. Acta Neurochir Suppl 63:109–114PubMedGoogle Scholar
  73. 73.
    Martinez R et al (1998) Pituitary tumors and gamma knife surgery. Clinical experience with more than two years of follow-up. Stereotact Funct Neurosurg 70(Suppl 1):110–118PubMedCrossRefGoogle Scholar
  74. 74.
    Inoue HK et al (1999) Pituitary adenomas treated by microsurgery with or without Gamma Knife surgery: experience in 122 cases. Stereotact Funct Neurosurg 72(Suppl 1):125–131PubMedCrossRefGoogle Scholar
  75. 75.
    Hall EJ (2000) Radiobiology for the radiologist, 5th edn. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  76. 76.
    Milker-Zabel S et al (2001) Fractionated stereotactically guided radiotherapy and radiosurgery in the treatment of functional and nonfunctional adenomas of the pituitary gland. Int J Radiat Oncol Biol Phys 50(5):1279–1286PubMedGoogle Scholar
  77. 77.
    Colin P et al (2005) Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients. Int J Radiat Oncol Biol Phys 62(2):333–341PubMedGoogle Scholar
  78. 78.
    Paek SH et al (2005) Integration of surgery with fractionated stereotactic radiotherapy for treatment of nonfunctioning pituitary macroadenomas. Int J Radiat Oncol Biol Phys 61(3):795–808PubMedGoogle Scholar
  79. 79.
    Minniti G et al (2006) Fractionated stereotactic conformal radiotherapy for secreting and nonsecreting pituitary adenomas. Clin Endocrinol (Oxf) 64(5):542–548CrossRefGoogle Scholar
  80. 80.
    McClelland S 3rd et al (2007) Fractionated stereotactic radiotherapy for pituitary adenomas following microsurgical resection: safety and efficacy. Technol Cancer Res Treat 6(3):177–180PubMedGoogle Scholar
  81. 81.
    Mackley HB et al (2007) Intensity-modulated radiotherapy for pituitary adenomas: the preliminary report of the Cleveland Clinic experience. Int J Radiat Oncol Biol Phys 67(1):232–239PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Andrew A. Kanner
    • 1
  • Benjamin W. Corn
    • 2
  • Yona Greenman
    • 3
    Email author
  1. 1.Stereotactic Radiosurgery Unit, Department of Neurosurgery, Tel Aviv-Sourasky Medical Center, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  2. 2.Institute of Radiotherapy, Tel Aviv-Sourasky Medical Center, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv-Sourasky Medical Center, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

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