Skip to main content

Advertisement

SpringerLink
Log in

Gamma knife radiosurgery for clinically persistent acromegaly

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Gamma knife radiosurgery (GKRS) is an important additional strategy for unresected clinically active pituitary adenomas. Radiosurgery for acromegaly aims to achieve tumor growth control and endocrine remission, potentially obviating the need for lifetime medication suppression therapy. Forty patients with clinically active acromegaly underwent GKRS between 1988 and 2009. Thirty-four patients had undergone prior surgical resection. The median follow-up interval was 72 months (range 24–145). Endocrine remission was defined as growth hormones (GH) level <2.5 ng/ml and a normal insulin-like growth factor 1 (IGF-1) level (age and sex adjusted) off growth hormone inhibiting drugs for at least 3 months. Endocrine control was defined as normal GH and IGF-1 levels on suppression medication. Endocrine remission was achieved in 19 (47.5 %) patients and endocrine control in four additional (10.0 %) patients. Patients with lower IGF-1 level and with tumors that were less invasive of the cavernous sinus before GKRS were associated with better GH remission rates. Imaging-defined local tumor control was achieved in 39 (97.5 %) patients (27 had tumor regression). One patient with delayed tumor progression underwent a second GKRS procedure. Three other patients had repeat GKRS because of persistently elevated and clinically symptomatic GH and IGF-1 levels. Sixteen (40.0 %) patients eventually developed a new pituitary axis deficiency at a median onset of 36 months after radiosurgery. No patient developed new visual dysfunction. Gamma knife radiosurgery, which is most often applied in clinically symptomatic acromegaly persistent after initial microsurgery, was most effective when the tumor was less invasive of the cavernous sinus and when patients had lower IGF-1 levels before GKRS. Almost one half of the patients no longer required long term medication suppression.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Holdaway IM, Rajasoorya C (1999) Epidemiology of acromegaly. Pituitary 2:29–41

    Article  PubMed  CAS  Google Scholar 

  2. Del Porto LA, Liubinas SV, Kaye AH (2011) Treatment of persistent and recurrent acromegaly. J Clin Neurosci 18:181–190

    Article  PubMed  Google Scholar 

  3. Laws ER, Vance ML, Thapar K (2000) Pituitary surgery for the management of acromegaly. Horm Res 53(Suppl 3):71–75

    Article  PubMed  CAS  Google Scholar 

  4. 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/Eur Fed Endocr Soc 152:379–387

    Article  CAS  Google Scholar 

  5. Laws ER (2008) Surgery for acromegaly: evolution of the techniques and outcomes. Rev Endocr Metab Disord 9:67–70

    Article  PubMed  Google Scholar 

  6. 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 

  7. 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 62:210–216

    Article  Google Scholar 

  8. 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 

  9. 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 64:588–595

    Article  Google Scholar 

  10. Bush ZM, Vance ML (2008) Management of acromegaly: is there a role for primary medical therapy? Rev Endocr Metab Disord 9:83–94

    Article  PubMed  Google Scholar 

  11. Thoren M, Rahn T, Guo WY, Werner S (1991) Stereotactic radiosurgery with the cobalt-60 gamma unit in the treatment of growth hormone-producing pituitary tumors. Neurosurgery 29:663–668

    Article  PubMed  CAS  Google Scholar 

  12. 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

    Article  PubMed  CAS  Google Scholar 

  13. 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 

  14. 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 

  15. Kobayashi T, Mori Y, Uchiyama Y, Kida Y, Fujitani S (2005) Long-term results of gamma knife surgery for growth hormone-producing pituitary adenoma: is the disease difficult to cure? J Neurosurg 102:119–123

    Article  PubMed  Google Scholar 

  16. 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 

  17. 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/Eur Fed Endocr Soc 157:255–263

    Article  CAS  Google Scholar 

  18. Jagannathan J, Sheehan JP, Pouratian N, Laws ER, Jr, Steiner L, Vance ML (2008) Gamma knife radiosurgery for acromegaly: outcomes after failed transsphenoidal surgery. Neurosurgery 62:1262–1269 (discussion 1269–1270)

    Article  PubMed  Google Scholar 

  19. Ronchi CL, Attanasio R, Verrua E, Cozzi R, Ferrante E, Loli P, Montefusco L, Motti E, Ferrari DI, Giugni E, Beck-Peccoz P, Arosio M (2009) Efficacy and tolerability of gamma knife radiosurgery in acromegaly: a 10-year follow-up study. Clin Endocrinol 71:846–852

    Article  Google Scholar 

  20. Iwai Y, Yamanaka K, Yoshimura M, Kawasaki I, Yamagami K, Yoshioka K (2010) Gamma knife radiosurgery for growth hormone-producing adenomas. J Clin Neurosci 17:299–304

    Article  PubMed  Google Scholar 

  21. Poon TL, Leung SC, Poon CY, Yu CP (2010) Predictors of outcome following Gamma Knife surgery for acromegaly. J Neurosurg 113(Suppl):149–152

    PubMed  Google Scholar 

  22. Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A (2009) Guidelines for acromegaly management: an update. J Clin Endocrinol Metab 94:1509–1517

    Article  PubMed  CAS  Google Scholar 

  23. Gutt B, Wowra B, Alexandrov R, Uhl E, Schaaf L, Stalla GK, Schopohl J (2005) Gamma-knife surgery is effective in normalising plasma insulin-like growth factor I in patients with acromegaly. Exp Clin Endocrinol Diabetes 113:219–224

    Article  PubMed  CAS  Google Scholar 

  24. Pouratian N, Sheehan J, Jagannathan J, Laws ER, Jr, Steiner L, Vance ML (2006) Gamma knife radiosurgery for medically and surgically refractory prolactinomas. Neurosurgery 59:255–266 (discussion 255–266)

    Article  PubMed  Google Scholar 

  25. Mercado M, Borges F, Bouterfa H, Chang TC, Chervin A, Farrall AJ, Patocs A, Petersenn S, Podoba J, Safari M, Wardlaw J (2007) A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly. Clin Endocrinol 66:859–868

    Article  CAS  Google Scholar 

  26. Buhk JH, Jung S, Psychogios MN, Goricke S, Hartz S, Schulz-Heise S, Klingebiel R, Forsting M, Bruckmann H, Dorfler A, Jordan M, Buchfelder M, Knauth M (2010) Tumor volume of growth hormone-secreting pituitary adenomas during treatment with pegvisomant: a prospective multicenter study. J Clinical Endocrinol Metab 95:552–558

    Article  CAS  Google Scholar 

  27. Yang LP, Keating GM (2010) Octreotide long-acting release (LAR): a review of its use in the management of acromegaly. Drugs 70:1745–1769

    Article  PubMed  CAS  Google Scholar 

  28. Marazuela M, Paniagua AE, Gahete MD, Lucas T, Alvarez-Escola C, Manzanares R, Cameselle-Teijeiro J, Luque-Ramirez M, Luque RM, Fernandez-Rodriguez E, Castano JP, Bernabeu I (2011) Somatotroph tumor progression during pegvisomant therapy: a clinical and molecular study. J Clin Endocrinol Metab 96:E251–E259

    Article  PubMed  CAS  Google Scholar 

  29. Ewins DL, Javaid A, Coskeran PB, Shah S, Butler J, Deprez PH, Miell J, Calam J, Barrett JJ, Dawson JM et al (1992) Assessment of gall bladder dynamics, cholecystokinin release and the development of gallstones during octreotide therapy for acromegaly. Q J Med 83:295–306

    PubMed  CAS  Google Scholar 

  30. Sheehan JP, Pouratian N, Steiner L, Laws ER, Vance ML (2011) Gamma Knife surgery for pituitary adenomas: factors related to radiological and endocrine outcomes. J Neurosurg 114:303–309

    Article  PubMed  Google Scholar 

  31. Fukuoka S, Ito T, Takanashi M, Hojo A, Nakamura H (2001) Gamma knife radiosurgery for growth hormone-secreting pituitary adenomas invading the cavernous sinus. Stereotact Funct Neurosurg 76:213–217

    Article  PubMed  CAS  Google Scholar 

  32. 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 

  33. Jackson IM, Noren G (1999) Role of gamma knife radiosurgery in acromegaly. Pituitary 2:71–77

    Article  PubMed  CAS  Google Scholar 

  34. 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 

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

    Article  CAS  Google Scholar 

  36. 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 55:183–189

    Article  CAS  Google Scholar 

  37. 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 

  38. Park KJ, Kano H, Parry PV, Niranjan A, Flickinger JC (2011) Lunsford LD. Long-term Outcomes after Gamma Knife Stereotactic Radiosurgery for Non-Functional Pituitary Adenomas. Neurosurgery, Kondziolka D

    Google Scholar 

  39. Feigl GC, Pistracher K, Berghold A, Mokry M (2010) Pituitary insufficiency as a side effect after radiosurgery for pituitary adenomas: the role of the hypothalamus. J Neurosurg 113(Suppl):153–159

    PubMed  CAS  Google Scholar 

  40. Leenstra JL, Tanaka S, Kline RW, Brown PD, Link MJ, Nippoldt TB, Young WF, Jr, Pollock BE (2010) Factors associated with endocrine deficits after stereotactic radiosurgery of pituitary adenomas. Neurosurgery 67:27–32 (discussion 32–23)

    Article  PubMed  Google Scholar 

  41. Rieger A, Rainov NG, Ebel H, Sanchin L, Shibib K, Helfrich C, Hoffmann O, Burkert W (1997) Factors predicting pituitary adenoma invasiveness in acromegalic patients. Neurosurg Rev 20:182–187

    Article  PubMed  CAS  Google Scholar 

  42. Thapar K, Kovacs K, Stefaneanu L, Scheithauer B, Killinger DW, Lioyd RV, Smyth HS, Barr A, Thorner MO, Gaylinn B, Laws ER Jr (1997) Overexpression of the growth-hormone-releasing hormone gene in acromegaly-associated pituitary tumors. An event associated with neoplastic progression and aggressive behavior. Am J pathol 151:769–784

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work described in this report was funded by a research grant to Dr. Kano from AB Elekta, Stockholm, Sweden and from the Osaka Medical Research Foundation for Incurable Diseases. Drs. Lunsford and Kondziolka are consultants for AB Elekta and Dr. Lunsford is a stockholder.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurological Surgery, University of Pittsburgh School of Medicine, University of Pittsburgh, Suite B-400, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Xiaomin Liu, Hideyuki Kano, Douglas Kondziolka, Kyung-Jae Park, Ajay Niranjan & L. Dade Lunsford

  2. Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Douglas Kondziolka, John C. Flickinger & L. Dade Lunsford

  3. Center for Image-Guided Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Xiaomin Liu, Hideyuki Kano, Douglas Kondziolka, Kyung-Jae Park, Ajay Niranjan, John C. Flickinger & L. Dade Lunsford

  4. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Aditya Iyer

  5. Department of Neurosurgery and Gamma Knife Center, 2nd Hospital of Tianjin Medical University, Tianjin, 300070, China

    Xiaomin Liu

  6. Department of Neurosurgery, College of Medicine, Korea University, Seoul, Korea

    Kyung-Jae Park

Authors
  1. Xiaomin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideyuki Kano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Douglas Kondziolka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyung-Jae Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aditya Iyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ajay Niranjan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John C. Flickinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L. Dade Lunsford
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Dade Lunsford.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, X., Kano, H., Kondziolka, D. et al. Gamma knife radiosurgery for clinically persistent acromegaly. J Neurooncol 109, 71–79 (2012). https://doi.org/10.1007/s11060-012-0862-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-012-0862-z

Keywords

Search

Navigation