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Radiotherapy and radiosurgery in acromegaly

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Abstract

Growth-hormone hypersecretion, acromegaly, is associated with reduced life expectancy. First line treatment remains surgery, but remission rates vary between 50% and 90%. In case of lack of surgical remission or recurrence, somatostatin agonists can be proposed. However, about 30% of patients are partially or totally resistant to this treatment. The growth hormone receptor antagonist pegvisomant currently needs more prolonged follow-up studies. Conventional radiotherapy and radiosurgery are two radiation treatment modalities that can be proposed to these resistant patients. Reported rates of remission for conventional radiotherapy range between 50% and 60% in patients with acromegaly, with a time to remission delayed by several years, and adverse effects including high rates of hypopituitarism. This treatment could be proposed to patients with aggressive adenomas, in whom surgery cannot allow biochemical control. In contrast, studies on stereotactic radiosurgery reported lower rates of remission, with faster growth hormone hypersecretion decline, and a lower risk of adverse effects. However, this latter technique requires a well defined target volume, which limits its indications. The high precision of this technique makes it possible to be used as an alternative primary treatment to surgery. We reviewed major advantages and drawbacks of each of these techniques, based on recent studies to try to define their respective indications in the therapeutic algorithm of acromegaly.

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Abbreviations

Gy:

Gray

GH:

Growth-hormone

References

  1. Melmed S (2006) Medical progress: acromegaly. N Engl J Med 355:2558–2573

    Article  PubMed  CAS  Google Scholar 

  2. Melmed S, Casanueva F, Cavagnini F, Chanson P, Frohman LA, Gaillard R, Ghigo E, Ho K, Jaquet P, Kleinberg D, Lamberts S, Laws E, Lombardi G, Sheppard MC, Thorner M, Vance ML, Wass JA, Giustina A (2005) Consensus statement: medical management of acromegaly. Eur J Endocrinol 153:737–740

    Article  PubMed  CAS  Google Scholar 

  3. Nomikos P, Buchfelder M, Fahlbusch R (2005) The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’. Eur J Endocrinol 152:379–387

    Article  PubMed  CAS  Google Scholar 

  4. Erturk E, Tuncel E, Kiyici S, Ersoy C, Duran C, Imamoglu S (2005) Outcome of surgery for acromegaly performed by different surgeons: importance of surgical experience. Pituitary 8:93–97

    Article  PubMed  Google Scholar 

  5. Shimon I, Cohen ZR, Ram Z, Hadani M (2001) Transsphenoidal surgery for acromegaly: endocrinological follow-up of 98 patients. Neurosurgery 48:1239–1243, discussion 1244–1235

    Article  PubMed  CAS  Google Scholar 

  6. Biermasz NR, van Dulken H, Roelfsema F (2000) Ten-year follow-up results of transsphenoidal microsurgery in acromegaly. J Clin Endocrinol Metab 85:4596–4602

    Article  PubMed  CAS  Google Scholar 

  7. Freda PU (2003) How effective are current therapies for acromegaly? Growth Horm IGF Res 13(Suppl A):S144–S151

    Article  PubMed  CAS  Google Scholar 

  8. Krieger MD, Couldwell WT, Weiss MH (2003) Assessment of long-term remission of acromegaly following surgery. J Neurosurg 98:719–724

    PubMed  Google Scholar 

  9. Freda PU (2002) Somatostatin analogs in acromegaly. J Clin Endocrinol Metab 87:3013–3018

    Article  PubMed  CAS  Google Scholar 

  10. Schreiber I, Buchfelder M, Droste M, Forssmann K, Mann K, Saller B, Strasburger CJ (2007) Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant observational study. Eur J Endocrinol 156:75–82

    Article  PubMed  CAS  Google Scholar 

  11. van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA, Thorner MO (2001) Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 358:1754–1759

    Article  PubMed  Google Scholar 

  12. Freda PU, Katznelson L, van der Lely AJ, Reyes CM, Zhao S, Rabinowitz D (2005) Long-acting somatostatin analog therapy of acromegaly: a meta-analysis. J Clin Endocrinol Metab 90:4465–4473

    Article  PubMed  CAS  Google Scholar 

  13. Eastman RC, Gorden P, Glatstein E, Roth J (1992) Radiation therapy of acromegaly. Endocrinol Metab Clin North Am 21:693–712

    PubMed  CAS  Google Scholar 

  14. Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S (2000) Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 85:526–529

    Article  PubMed  CAS  Google Scholar 

  15. Giustina A, Casanueva FF, Cavagnini F, Chanson P, Clemmons D, Frohman LA, Gaillard R, Ho K, Jaquet P, Kleinberg DL, Lamberts SW, Lombardi G, Sheppard M, Strasburger CJ, Vance ML, Wass JA, Melmed S (2003) Diagnosis and treatment of acromegaly complications. J Endocrinol Invest 26:1242–1247

    PubMed  CAS  Google Scholar 

  16. Bates AS, Van’t Hoff W, Jones JM, Clayton RN (1993) An audit of outcome of treatment in acromegaly. Q J Med 86:293–299

    PubMed  CAS  Google Scholar 

  17. Barkan AL, Halasz I, Dornfeld KJ, Jaffe CA, Friberg RD, Chandler WF, Sandler HM (1997) Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. J Clin Endocrinol Metab 82:3187–3191

    Article  PubMed  CAS  Google Scholar 

  18. Powell JS, Wardlaw SL, Post KD, Freda PU (2000) Outcome of radiotherapy for acromegaly using normalization of insulin-like growth factor I to define cure. J Clin Endocrinol Metab 85:2068–2071

    Article  PubMed  CAS  Google Scholar 

  19. Biermasz NR, van Dulken H, Roelfsema F (2000) Long-term follow-up results of postoperative radiotherapy in 36 patients with acromegaly. J Clin Endocrinol Metab 85:2476–2482

    Article  PubMed  CAS  Google Scholar 

  20. Epaminonda P, Porretti S, Cappiello V, Beck-Peccoz P, Faglia G, Arosio M (2001) Efficacy of radiotherapy in normalizing serum IGF-I, acid-labile subunit (ALS) and IGFBP-3 levels in acromegaly. Clin Endocrinol (Oxf) 55:183–189

    Article  CAS  Google Scholar 

  21. Barrande G, Pittino-Lungo M, Coste J, Ponvert D, Bertagna X, Luton JP, Bertherat J (2000) Hormonal and metabolic effects of radiotherapy in acromegaly: long-term results in 128 patients followed in a single center. J Clin Endocrinol Metab 85:3779–3785

    Article  PubMed  CAS  Google Scholar 

  22. Cozzi R, Barausse M, Asnaghi D, Dallabonzana D, Lodrini S, Attanasio R (2001) Failure of radiotherapy in acromegaly. Eur J Endocrinol 145:717–726

    Article  PubMed  CAS  Google Scholar 

  23. Minniti G, Jaffrain-Rea ML, Osti M, Esposito V, Santoro A, Solda F, Gargiulo P, Tamburrano G, Enrici RM (2005) The long-term efficacy of conventional radiotherapy in patients with GH-secreting pituitary adenomas. Clin Endocrinol (Oxf) 62:210–216

    Article  Google Scholar 

  24. Jenkins PJ, Bates P, Carson MN, Stewart PM, Wass JA (2006) Conventional pituitary irradiation is effective in lowering serum growth hormone and insulin-like growth factor-I in patients with acromegaly. J Clin Endocrinol Metab 91:1239–1245

    Article  PubMed  CAS  Google Scholar 

  25. Jallad RS, Musolino NR, Salgado LR, Bronstein MD (2007) Treatment of acromegaly: is there still a place for radiotherapy? Pituitary 10:53–59

    Article  PubMed  Google Scholar 

  26. Jaffe CA (1999) Reevaluation of conventional pituitary irradiation in the therapy of acromegaly. Pituitary 2:55–62

    Article  PubMed  CAS  Google Scholar 

  27. Erfurth EM, Bulow B, Mikoczy Z, Svahn-Tapper G, Hagmar L (2001) Is there an increase in second brain tumours after surgery and irradiation for a pituitary tumour? Clin Endocrinol (Oxf) 55:613–616

    Article  CAS  Google Scholar 

  28. Minniti G, Traish D, Ashley S, Gonsalves A, Brada M (2005) Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years. J Clin Endocrinol Metab 90:800–804

    Article  PubMed  CAS  Google Scholar 

  29. Erfurth EM, Bulow B, Svahn-Tapper G, Norrving B, Odh K, Mikoczy Z, Bjork J, Hagmar L (2002) Risk factors for cerebrovascular deaths in patients operated and irradiated for pituitary tumors. J Clin Endocrinol Metab 87:4892–4899

    Article  PubMed  CAS  Google Scholar 

  30. McCord MW, Buatti JM, Fennell EM, Mendenhall WM, Marcus RB Jr, Rhoton AL, Grant MB, Friedman WA (1997) Radiotherapy for pituitary adenoma: long-term outcome and sequelae. Int J Radiat Oncol Biol Phys 39:437–444

    PubMed  CAS  Google Scholar 

  31. Peace KA, Orme SM, Padayatty SJ, Godfrey HP, Belchetz PE (1998) Cognitive dysfunction in patients with pituitary tumour who have been treated with transfrontal or transsphenoidal surgery or medication. Clin Endocrinol (Oxf) 49:391–396

    Article  CAS  Google Scholar 

  32. Noad R, Narayanan KR, Howlett T, Lincoln NB, Page RC (2004) Evaluation of the effect of radiotherapy for pituitary tumours on cognitive function and quality of life. Clin Oncol (R Coll Radiol) 16:233–237

    CAS  Google Scholar 

  33. Pan L, Zhang N, Wang E, Wang B, Xu W (1998) Pituitary adenomas: the effect of gamma knife radiosurgery on tumor growth and endocrinopathies. Stereotact Funct Neurosurg 70(Suppl 1):119–126

    Article  PubMed  Google Scholar 

  34. Lim YL, Leem W, Kim TS, Rhee BA, Kim GK (1998) Four years’ experiences in the treatment of pituitary adenomas with gamma knife radiosurgery. Stereotact Funct Neurosurg 70 Suppl 1:95–109

    Article  Google Scholar 

  35. Landolt AM, Haller D, Lomax N, Scheib S, Schubiger O, Siegfried J, Wellis G (1998) Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison with fractionated radiotherapy. J Neurosurg 88:1002–1008

    Article  PubMed  CAS  Google Scholar 

  36. Hayashi M, Izawa M, Hiyama H, Nakamura S, Atsuchi S, Sato H, Nakaya K, Sasaki K, Ochiai T, Kubo O, Hori T, Takakura K (1999) Gamma knife radiosurgery for pituitary adenomas. Stereotact Funct Neurosurg 72(Suppl 1):111–118

    Article  PubMed  Google Scholar 

  37. Mokry M, Ramschak-Schwarzer S, Simbrunner J, Ganz JC, Pendl G (1999) A six year experience with the postoperative radiosurgical management of pituitary adenomas. Stereotact Funct Neurosurg 72(Suppl 1):88–100

    Article  PubMed  Google Scholar 

  38. Kim SH, Huh R, Chang JW, Park YG, Chung SS (1999) Gamma knife radiosurgery for functioning pituitary adenomas. Stereotact Funct Neurosurg 72(Suppl 1):101–110

    Article  PubMed  Google Scholar 

  39. Inoue HK, Kohga H, Hirato M, Sasaki T, Ishihara J, Shibazaki T, Ohye C, Andou Y (1999) Pituitary adenomas treated by microsurgery with or without gamma knife surgery: experience in 122 cases. Stereotact Funct Neurosurg 72(Suppl 1):125–131

    Article  PubMed  Google Scholar 

  40. Izawa M, Hayashi M, Nakaya K, Satoh H, Ochiai T, Hori T, Takakura K (2000) Gamma knife radiosurgery for pituitary adenomas. J Neurosurg 93(Suppl 3):19–22

    PubMed  Google Scholar 

  41. Zhang N, Pan L, Wang EM, Dai JZ, Wang BJ, Cai PW (2000) Radiosurgery for growth hormone-producing pituitary adenomas. J Neurosurg 93(Suppl 3):6–9

    PubMed  Google Scholar 

  42. Ikeda H, Jokura H, Yoshimoto T (2001) Transsphenoidal surgery and adjuvant gamma knife treatment for growth hormone-secreting pituitary adenoma. J Neurosurg 95:285–291

    PubMed  CAS  Google Scholar 

  43. Choi JY, Chang JH, Chang JW, Ha Y, Park YG, Chung SS (2003) Radiological and hormonal responses of functioning pituitary adenomas after gamma knife radiosurgery. Yonsei Med J 44:602–607

    PubMed  Google Scholar 

  44. Attanasio R, Epaminonda P, Motti E, Giugni E, Ventrella L, Cozzi R, Farabola M, Loli P, Beck-Peccoz P, Arosio M (2003) Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. J Clin Endocrinol Metab 88:3105–3112

    Article  PubMed  CAS  Google Scholar 

  45. Castinetti F, Taieb D, Kuhn JM, Chanson P, Tamura M, Jaquet P, Conte-Devolx B, Regis J, Dufour H, Brue T (2005) Outcome of gamma knife radiosurgery in 82 patients with acromegaly: correlation with initial hypersecretion. J Clin Endocrinol Metab 90:4483–4488

    Article  PubMed  CAS  Google Scholar 

  46. Jezkova J, Marek J, Hana V, Krsek M, Weiss V, Vladyka V, Lisak R, Vymazal J, Pecen L (2006) Gamma knife radiosurgery for acromegaly-long-term experience. Clin Endocrinol (Oxf) 64:588–595

    Article  Google Scholar 

  47. Pollock BE, Jacob JT, Brown PD, Nippoldt TB (2007) Radiosurgery of growth hormone-producing pituitary adenomas: factors associated with biochemical remission. J Neurosurg 106:833–838

    Article  PubMed  CAS  Google Scholar 

  48. Vik-Mo EO, Oksnes M, Pedersen PH, Wentzel-Larsen T, Rodahl E, Thorsen F, Schreiner T, Aanderud S, Lund-Johansen M (2007) Gamma knife stereotactic radiosurgery for acromegaly. Eur J Endocrinol 157:255–263

    Article  PubMed  CAS  Google Scholar 

  49. Landolt AM, Haller D, Lomax N, Scheib S, Schubiger O, Siegfried J, Wellis G (2000) Octreotide may act as a radioprotective agent in acromegaly. J Clin Endocrinol Metab 85:1287–1289

    Article  PubMed  CAS  Google Scholar 

  50. Brada M, Ajithkumar TV, Minniti G (2004) Radiosurgery for pituitary adenomas. Clin Endocrinol (Oxf) 61:531–543

    Article  CAS  Google Scholar 

  51. Laws ER, Sheehan JP, Sheehan JM, Jagnathan J, Jane JA Jr, Oskouian R (2004) Stereotactic radiosurgery for pituitary adenomas: a review of the literature. J Neurooncol 69:257–272

    Article  PubMed  Google Scholar 

  52. Hoybye C, Grenback E, Rahn T, Degerblad M, Thoren M, Hulting AL (2001) Adrenocorticotropic hormone-producing pituitary tumors: 12- to 22-year follow-up after treatment with stereotactic radiosurgery. Neurosurgery 49:284–291, discussion 291–282

    Article  PubMed  CAS  Google Scholar 

  53. Mahmoud-Ahmed AS, Suh JH, Mayberg MR (2001) Gamma knife radiosurgery in the management of patients with acromegaly: a review. Pituitary 4:223–230

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology, La Timone Hospital, Assistance Publique-Hôpitaux de Marseille and Université de la Mediterranée, Marseille, France

    Frédéric Castinetti, Isabelle Morange & Thierry Brue

  2. Department of Neurosurgery, La Timone Hospital, Assistance Publique-Hôpitaux de Marseille and Université de la Mediterranée, Marseille, France

    Henry Dufour

  3. Department of Stereotactic Neurosurgery, La Timone Hospital, Assistance Publique-Hôpitaux de Marseille and Université de la Mediterranée, Marseille, France

    Jean Regis

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  1. Frédéric Castinetti
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  2. Isabelle Morange
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  3. Henry Dufour
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  5. Thierry Brue
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Correspondence to Thierry Brue.

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Castinetti, F., Morange, I., Dufour, H. et al. Radiotherapy and radiosurgery in acromegaly. Pituitary 12, 3–10 (2009). https://doi.org/10.1007/s11102-007-0078-y

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