, Volume 52, Issue 3, pp 451–457 | Cite as

Pros and cons in endocrine practice: pre-surgical treatment with somatostatin analogues in acromegaly

  • Marco LosaEmail author
  • Jens Bollerslev
Pros and Cons in Endocrine Practice


The aim of this commentary is to balance the pros and cons for pre-surgical SSA treatment in a modern perspective ending up with a pragmatic recommendation for treatment based on the current evidence and expertise of the authors. Even though prospective and randomized studies in this particular area are hampered by obvious limitations, the interpretation of the four published trials has in general been in favor of pre-treatment with SSA, showing a better outcome following surgery. However, major drawbacks of these studies, such as non-optimal diagnostic criteria for cure, potential selection bias, and timing of the postoperative evaluation in SSA pre-treated patients, limit their overall interpretation. Three matched-controlled studies showed remarkably similar results with no apparent beneficial effect of SSA pre-treatment on surgical outcome. Both prospective, randomized studies and retrospective studies did not find any significant difference in the rate of endocrine and non-endocrine complications related to surgery, despite the beneficial clinical effects of SSA treatment in most acromegalic patients. The newly diagnosed patient with acromegaly should be carefully evaluated in the trans-disciplinary neuroendocrine team and treatment individualized accordingly. The issue of SSA pre-treatment to improve surgical outcome is yet to be settled and further methodologically sound studies are probably necessary to clarify this point.


Acromegaly Somatostatin analogues Pituitary neoplasms Pituitary surgery 



First generation somatostatin analogue


Dopamine agonist




Transsphenoidal surgery




Conflict of interest

The authors have nothing to declare.


  1. 1.
    L. Katznelson, E.R. Laws Jr, S. Melmed, M.E. Molitch, M.H. Murad, A. Utz et al., Acromegaly: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99(11), 3933–3951 (2014). doi: 10.1210/jc.2014-2700 CrossRefPubMedGoogle Scholar
  2. 2.
    S. Melmed, A. Colao, A. Barkan, M. Molitch, A.B. Grossman, D. Kleinberg et al., Guidelines for acromegaly management: an update. J. Clin. Endocrinol. Metab. 94(5), 1509–1517 (2009). doi: 10.1210/jc.2008-2421 CrossRefPubMedGoogle Scholar
  3. 3.
    M. Fleseriu, A.R. Hoffman, L. Katznelson, American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: management of acromegaly patients: what is the role of pre-operative medical therapy? Endocr. Pract. 21(6), 668–673 (2015). doi: 10.4158/EP14575.DSCR CrossRefPubMedGoogle Scholar
  4. 4.
    A. Giustina, P. Chanson, D. Kleinberg, M.D. Bronstein, D.R. Clemmons, A. Klibanski et al., Expert consensus document: a consensus on the medical treatment of acromegaly. Nat. Rev. Endocrinol. 10(4), 243–248 (2014). doi: 10.1038/nrendo.2014.21 CrossRefPubMedGoogle Scholar
  5. 5.
    P. Nomikos, M. Buchfelder, R. Fahlbusch, The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’. Eur. J. Endocrinol. 152(3), 379–387 (2005). doi: 10.1530/eje.1.01863 CrossRefPubMedGoogle Scholar
  6. 6.
    P. Mortini, M. Losa, R. Barzaghi, N. Boari, M. Giovanelli, Results of transsphenoidal surgery in a large series of patients with pituitary adenoma. Neurosurgery 56(6), 1222–1233 (2005). discussion 33 CrossRefPubMedGoogle Scholar
  7. 7.
    C.R. Ku, E.H. Kim, M.C. Oh, E.J. Lee, S.H. Kim, Surgical and endocrinological outcomes in the treatment of growth hormone-secreting pituitary adenomas according to the shift of surgical paradigm. Neurosurgery 71(2 Suppl Operative), ons192–ons203 (2012). doi: 10.1227/NEU.0b013e318265a288. discussion ons203 PubMedGoogle Scholar
  8. 8.
    D.B. Hazer, S. Isik, D. Berker, S. Guler, A. Gurlek, T. Yucel et al., Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria. J. Neurosurg. 119(6), 1467–1477 (2013). doi: 10.3171/2013.8.JNS13224 CrossRefPubMedGoogle Scholar
  9. 9.
    Y.Y. Wang, C. Higham, T. Kearney, J.R. Davis, P. Trainer, K.K. Gnanalingham, Acromegaly surgery in Manchester revisited—the impact of reducing surgeon numbers and the 2010 consensus guidelines for disease remission. Clin. Endocrinol. (Oxf). 76(3), 399–406 (2012). doi: 10.1111/j.1365-2265.2011.04193.x CrossRefPubMedGoogle Scholar
  10. 10.
    A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva et al., A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95(7), 3141–3148 (2010). doi: 10.1210/jc.2009-2670 CrossRefPubMedGoogle Scholar
  11. 11.
    P.U. Freda, L. Katznelson, A.J. van der Lely, C.M. Reyes, S. Zhao, D. Rabinowitz, Long-acting somatostatin analog therapy of acromegaly: a meta-analysis. J. Clin. Endocrinol. Metab. 90(8), 4465–4473 (2005)CrossRefPubMedGoogle Scholar
  12. 12.
    A.L. Barkan, R.V. Lloyd, W.F. Chandler, M.K. Hatfield, S.S. Gebarski, R.P. Kelch et al., Preoperative treatment of acromegaly with long-acting somatostatin analog SMS 201-995: shrinkage of invasive pituitary macroadenomas and improved surgical remission rate. J. Clin. Endocrinol. Metab. 67(5), 1040–1048 (1988)CrossRefPubMedGoogle Scholar
  13. 13.
    S. Bacigaluppi, F. Gatto, P. Anania, N.L. Bragazzi, D.C. Rossi, G. Benvegnu et al., Impact of pre-treatment with somatostatin analogs on surgical management of acromegalic patients referred to a single center. Endocrine (2015). doi: 10.1007/s12020-015-0619-5 PubMedGoogle Scholar
  14. 14.
    M. Bex, R. Abs, G. T’Sjoen, J. Mockel, B. Velkeniers, K. Muermans et al., AcroBel—the Belgian registry on acromegaly: a survey of the ‘real-life’ outcome in 418 acromegalic subjects. Eur. J. Endocrinol. 157(4), 399–409 (2007)CrossRefPubMedGoogle Scholar
  15. 15.
    G. Sesmilo, S. Gaztambide, E. Venegas, A. Pico, C. Del Pozo, C. Blanco et al., Changes in acromegaly treatment over four decades in Spain: analysis of the Spanish Acromegaly Registry (REA). Pituitary 16(1), 115–121 (2013). doi: 10.1007/s11102-012-0384-x CrossRefPubMedGoogle Scholar
  16. 16.
    A. Giustina, M.D. Bronstein, F.F. Casanueva, P. Chanson, E. Ghigo, K.K. Ho et al., Current management practices for acromegaly: an international survey. Pituitary 14(2), 125–133 (2011). doi: 10.1007/s11102-010-0269-9 CrossRefPubMedGoogle Scholar
  17. 17.
    S.M. Carlsen, M. Lund-Johansen, T. Schreiner, S. Aanderud, O. Johannesen, J. Svartberg et al., Preoperative octreotide treatment in newly diagnosed acromegalic patients with macroadenomas increases cure short-term postoperative rates: a prospective, randomized trial. J. Clin. Endocrinol. Metab. 93(8), 2984–2990 (2008). doi: 10.1210/jc.2008-0315 CrossRefPubMedGoogle Scholar
  18. 18.
    Z.G. Mao, Y.H. Zhu, H.L. Tang, D.Y. Wang, J. Zhou, D.S. He et al., Preoperative lanreotide treatment in acromegalic patients with macroadenomas increases short-term postoperative cure rates: a prospective, randomised trial. Eur. J. Endocrinol. 162(4), 661–666 (2010). doi: 10.1530/EJE-09-0908 CrossRefPubMedGoogle Scholar
  19. 19.
    Z.Q. Li, Z. Quan, H.L. Tian, M. Cheng, Preoperative lanreotide treatment improves outcome in patients with acromegaly resulting from invasive pituitary macroadenoma. J. Int. Med. Res. 40(2), 517–524 (2012). doi: 10.1177/147323001204000213 CrossRefPubMedGoogle Scholar
  20. 20.
    M. Shen, X. Shou, Y. Wang, Z. Zhang, J. Wu, Y. Mao et al., Effect of presurgical long-acting octreotide treatment in acromegaly patients with invasive pituitary macroadenomas: a prospective randomized study. Endocr. J. 57(12), 1035–1044 (2010)CrossRefPubMedGoogle Scholar
  21. 21.
    D. Ferone, F. Gatto, F. Minuto, Pre-surgical treatment with somatostatin analogues in patients with acromegaly: the case for. J. Endocrinol. Invest. 35(6), 613–615 (2012)CrossRefPubMedGoogle Scholar
  22. 22.
    S.L. Fougner, O.C. Borota, J.P. Berg, J.K. Hald, J. Ramm-Pettersen, J. Bollerslev, The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma. Clin. Endocrinol. (Oxf). 68(3), 458–465 (2008)CrossRefPubMedGoogle Scholar
  23. 23.
    S.L. Fougner, O. Casar-Borota, A. Heck, J.P. Berg, J. Bollerslev, Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly. Clin. Endocrinol. (Oxf). 76(1), 96–102 (2012). doi: 10.1111/j.1365-2265.2011.04163.x CrossRefPubMedGoogle Scholar
  24. 24.
    S.L. Fougner, T. Lekva, O.C. Borota, J.K. Hald, J. Bollerslev, J.P. Berg, The expression of E-cadherin in somatotroph pituitary adenomas is related to tumor size, invasiveness, and somatostatin analog response. J. Clin. Endocrinol. Metab. 95(5), 2334–2342 (2010). doi: 10.1210/jc.2009-2197 CrossRefPubMedGoogle Scholar
  25. 25.
    O. Casar-Borota, A. Heck, S. Schulz, J.M. Nesland, J. Ramm-Pettersen, T. Lekva et al., Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas assessed by monoclonal antibodies was reduced by octreotide and correlated with the acute and long-term effects of octreotide. J. Clin. Endocrinol. Metab. 98(11), E1730–E1739 (2013). doi: 10.1210/jc.2013-2145 CrossRefPubMedGoogle Scholar
  26. 26.
    A. Heck, K.E. Emblem, O. Casar-Borota, J. Bollerslev, G. Ringstad, Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly. Endocrine (2015). doi: 10.1007/s12020-015-0766-8 Google Scholar
  27. 27.
    A. Heck, G. Ringstad, S.L. Fougner, O. Casar-Borota, T. Nome, J. Ramm-Pettersen et al., Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly. Clin. Endocrinol. (Oxf). 77(1), 72–78 (2012). doi: 10.1111/j.1365-2265.2011.04286.x CrossRefPubMedGoogle Scholar
  28. 28.
    A. Beckers, Does preoperative somatostatin analog treatment improve surgical cure rates in acromegaly? A new look at an old question. J. Clin. Endocrinol. Metab. 93(8), 2975–2977 (2008). doi: 10.1210/jc.2008-1351 CrossRefPubMedGoogle Scholar
  29. 29.
    M. Losa, V.G. Crippa, Pre-surgical treatment with somatostatin analogues in patients with acromegaly: the case against. J. Endocrinol. Invest. 35(6), 616–618 (2012)CrossRefPubMedGoogle Scholar
  30. 30.
    F. Pita-Gutierrez, S. Pertega-Diaz, S. Pita-Fernandez, L. Pena, G. Lugo, S. Sangiao-Alvarellos et al., Place of preoperative treatment of acromegaly with somatostatin analog on surgical outcome: a systematic review and meta-analysis. PLoS One 8(4), e61523 (2013). doi: 10.1371/journal.pone.0061523 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    A.K. Flogstad, J. Halse, T. Haldorsen, I. Lancranjan, P. Marbach, C. Bruns et al., Sandostatin LAR in acromegalic patients: a dose-range study. J. Clin. Endocrinol. Metab. 80(12), 3601–3607 (1995)PubMedGoogle Scholar
  32. 32.
    S.L. Fougner, J. Bollerslev, J. Svartberg, M. Oksnes, J. Cooper, S.M. Carlsen, Preoperative octreotide treatment of acromegaly: long-term results of a randomised controlled trial. Eur. J. Endocrinol. 171(2), 229–235 (2014). doi: 10.1530/EJE-14-0249 CrossRefPubMedGoogle Scholar
  33. 33.
    L. Zhang, X. Wu, Y. Yan, J. Qian, Y. Lu, C. Luo, Preoperative somatostatin analogs treatment in acromegalic patients with macroadenomas. A meta-analysis. Brain Dev. 37(2), 181–190 (2015). doi: 10.1016/j.braindev.2014.04.009 CrossRefPubMedGoogle Scholar
  34. 34.
    V.S. Nunes, J.M. Correa, M.E. Puga, E.M. Silva, C.L. Boguszewski, Preoperative somatostatin analogues versus direct transsphenoidal surgery for newly-diagnosed acromegaly patients: a systematic review and meta-analysis using the GRADE system. Pituitary 18(4), 500–508 (2015). doi: 10.1007/s11102-014-0602-9 CrossRefPubMedGoogle Scholar
  35. 35.
    U. Plockinger, H.J. Quabbe, Presurgical octreotide treatment in acromegaly: no improvement of final growth hormone (GH) concentration and pituitary function. A long-term case-control study. Acta Neurochir (Wien). 147(5), 485–493 (2005). doi: 10.1007/s00701-005-0511-9. discussion 93 CrossRefPubMedGoogle Scholar
  36. 36.
    N.R. Biermasz, H. van Dulken, F. Roelfsema, Direct postoperative and follow-up results of transsphenoidal surgery in 19 acromegalic patients pretreated with octreotide compared to those in untreated matched controls. J. Clin. Endocrinol. Metab. 84(10), 3551–3555 (1999)CrossRefPubMedGoogle Scholar
  37. 37.
    M. Losa, P. Mortini, L. Urbaz, P. Ribotto, T. Castrignanò, M. Giovanelli, Presurgical treatment with somatostatin analogs in patients with acromegaly: effects on the remission and complication rates. J. Neurosurg. 104(6), 899–906 (2006)CrossRefPubMedGoogle Scholar
  38. 38.
    A. Colao, D. Ferone, P. Cappabianca, M.L. del Basso De Caro, P. Marzullo, A. Monticelli et al., Effect of octreotide pretreatment on surgical outcome in acromegaly. J. Clin. Endocrinol. Metab. 82(10), 3308–3314 (1997)CrossRefPubMedGoogle Scholar
  39. 39.
    T. Abe, D.K. Ludecke, Effects of preoperative octreotide treatment on different subtypes of 90 GH-secreting pituitary adenomas and outcome in one surgical centre. Eur. J. Endocrinol. 145(2), 137–145 (2001)CrossRefPubMedGoogle Scholar
  40. 40.
    A. Stevenaert, A. Beckers, Presurgical Octreotide: treatment in acromegaly. Metabolism 45(8 Suppl 1), 72–74 (1996)CrossRefPubMedGoogle Scholar
  41. 41.
    S. Petersenn, M. Buchfelder, M. Reincke, C.M. Strasburger, H. Franz, R. Lohmann et al., Results of surgical and somatostatin analog therapies and their combination in acromegaly: a retrospective analysis of the German Acromegaly Register. Eur. J. Endocrinol. 159(5), 525–532 (2008). doi: 10.1530/EJE-08-0498 CrossRefPubMedGoogle Scholar
  42. 42.
    S.M. Carlsen, J. Svartberg, T. Schreiner, S. Aanderud, O. Johannesen, S. Skeie et al., Six-month preoperative octreotide treatment in unselected, de novo patients with acromegaly: effect on biochemistry, tumour volume, and postoperative cure. Clin. Endocrinol. (Oxf). 74(6), 736–743 (2011). doi: 10.1111/j.1365-2265.2011.03982.x CrossRefPubMedGoogle Scholar
  43. 43.
    A. Colao, R.S. Auriemma, M. Galdiero, G. Lombardi, R. Pivonello, Effects of initial therapy for five years with somatostatin analogs for acromegaly on growth hormone and insulin-like growth factor-I levels, tumor shrinkage, and cardiovascular disease: a prospective study. J. Clin. Endocrinol. Metab. 94(10), 3746–3756 (2009). doi: 10.1210/jc.2009-0941 CrossRefPubMedGoogle Scholar
  44. 44.
    M. Andries, D. Glintborg, A. Kvistborg, C. Hagen, M. Andersen, A 12-month randomized crossover study on the effects of lanreotide Autogel and octreotide long-acting repeatable on GH and IGF-l in patients with acromegaly. Clin. Endocrinol. (Oxf). 68(3), 473–480 (2008)CrossRefPubMedGoogle Scholar
  45. 45.
    H. Schmitt, M. Buchfelder, M. Radespiel-Troger, R. Fahlbusch, Difficult intubation in acromegalic patients: incidence and predictability. Anesthesiology 93(1), 110–114 (2000)CrossRefPubMedGoogle Scholar
  46. 46.
    S. Larkin, R. Reddy, N. Karavitaki, S. Cudlip, J. Wass, O. Ansorge, Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naive patients with somatotroph adenomas. Eur. J. Endocrinol. 168(4), 491–499 (2013). doi: 10.1530/EJE-12-0864 CrossRefPubMedGoogle Scholar
  47. 47.
    T. Lekva, J.P. Berg, A. Heck, S. Lyngvi Fougner, O.K. Olstad, G. Ringstad et al., Attenuated RORC expression in the presence of EMT progression in somatotroph adenomas following treatment with somatostatin analogs is associated with poor clinical recovery. PLoS One 8(6), e66927 (2013). doi: 10.1371/journal.pone.0066927 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    A. Colao, M.D. Bronstein, P. Freda, F. Gu, C.C. Shen, M. Gadelha et al., Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J. Clin. Endocrinol. Metab. 99(3), 791–799 (2014). doi: 10.1210/jc.2013-2480 PubMedPubMedCentralGoogle Scholar
  49. 49.
    M.R. Gadelha, M.D. Bronstein, T. Brue, M. Coculescu, M. Fleseriu, M. Guitelman et al., Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2(11), 875–884 (2014). doi: 10.1016/S2213-8587(14)70169-X CrossRefPubMedGoogle Scholar
  50. 50.
    M. Puig Domingo, Treatment of acromegaly in the era of personalized and predictive medicine. Clin. Endocrinol. (Oxf). 83(1), 3–14 (2015). doi: 10.1111/cen.12731 CrossRefPubMedGoogle Scholar
  51. 51.
    M. Puig-Domingo, E. Resmini, B. Gomez-Anson, J. Nicolau, M. Mora, E. Palomera et al., Magnetic resonance imaging as a predictor of response to somatostatin analogs in acromegaly after surgical failure. J. Clin. Endocrinol. Metab. 95(11), 4973–4978 (2010). doi: 10.1210/jc.2010-0573 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Pituitary Unit, Department of Neurosurgery, Istituto Scientifico San RaffaeleUniversità Vita-SaluteMilanItaly
  2. 2.Section of Specialized Endocrinology, Medical Clinic BOslo University HospitalOsloNorway
  3. 3.Faculty of MedicineUniversity in OsloOsloNorway

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