Endocrine

pp 1–8 | Cite as

Predictors of surgical outcome and early criteria of remission in acromegaly

  • Ximene Antunes
  • Nina Ventura
  • Gustavo Bittencourt Camilo
  • Luiz Eduardo Wildemberg
  • Andre Guasti
  • Paulo José M. Pereira
  • Aline Helen Silva Camacho
  • Leila Chimelli
  • Paulo Niemeyer
  • Mônica R. Gadelha
  • Leandro Kasuki
Endocrine Surgery
  • 34 Downloads

Abstract

Background

Transsphenoidal surgery (TSS) is the cornerstone of acromegaly treatment, however there are no robust predictors of surgical outcome and remission can only be defined three months after surgery.

Purpose

To analyze if biochemical, demographical, radiological, and immunohistochemical characteristics are predictors of surgical remission and investigate if immediate postoperative GH and IGF-I levels can help defining remission earlier.

Methods

Consecutive acromegaly patients submitted to TSS between 2013-2016 were evaluated. Remission criteria was defined as normal IGF-I and GH <1 mcg/L three months after surgery. Data of age, sex, GH and IGF-I levels, tumor volume, cavernous sinus invasion, T2-weighted signal, Ki-67, and granulation pattern were correlated with remission status. GH and IGF-I levels at 24, 48 h, and one week postoperative were evaluated as early criteria of remission.

Results

Sixty-nine patients were included (84% macroadenomas) and surgical remission was achieved in 45%. No difference between cured and not cured patients concerning age, gender, preoperative GH or IGF-I levels, tumor volume, T2-weighted signal, Ki-67 and tumor granularity was observed. Remission was obtained in 20 of 36 (56%) of the non-invasive tumors, and in 3 of 16 (19%) of the invasive tumors (p = 0.017). A GH <1.57 mcg/L 48 h after surgery was able to predict remission with 93% sensitivity and 86% specificity and an IGF-I < 231% ULNR one week after surgery predicted remission with 86% sensitivity and 93% specificity.

Conclusion

Cavernous sinus invasion is the only preoperative predictor of surgical remission. GH at 48 h and IGF-I one week after surgery can define earlier not cured patients.

Key words

Acromegaly Surgery Predictors of surgical outcome Early criteria of remission 

Notes

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12020_2018_1590_MOESM1_ESM.docx (19 kb)
Supplementary Table

References

  1. 1.
    L. Katznelson, E.R. Laws Jr., S. Melmed, M.E. Molitch, M.H. Murad, A. Utz, J.A. Wass, S. Endocrine, Acromegaly: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99(11), 3933–3951 (2014).  https://doi.org/10.1210/jc.2014-2700 CrossRefPubMedGoogle Scholar
  2. 2.
    S.M.S. Michael Buchfelder, The surgical treatment of acromegaly. Pituitary (2016).  https://doi.org/10.1007/s11102-016-0765-7
  3. 3.
    J.A. Jane Jr., R.M. Starke, M.A. Elzoghby, D.L. Reames, S.C. Payne, M.O. Thorner, J.C. Marshall, E.R. Laws Jr., M.L. Vance, Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J. Clin. Endocrinol. Metab. 96(9), 2732–2740 (2011).  https://doi.org/10.1210/jc.2011-0554 CrossRefPubMedGoogle Scholar
  4. 4.
    P. Petrossians, L. Borges-Martins, C. Espinoza, A. Daly, D. Betea, H. Valdes-Socin, A. Stevenaert, P. Chanson, A. Beckers, Gross total resection or debulking of pituitary adenomas improves hormonal control of acromegaly by somatostatin analogs. Eur. J. Endocrinol. 152(1), 61–66 (2005)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).  https://doi.org/10.1530/eje.1.01863 CrossRefPubMedGoogle Scholar
  6. 6.
    H. Sun, J. Brzana, C.G. Yedinak, S.H. Gultekin, J.B. Delashaw, M. Fleseriu, Factors associated with biochemical remission after microscopic transsphenoidal surgery for acromegaly. Journal of neurological surgery. Part B. Skull Base 75(1), 47–52 (2014).  https://doi.org/10.1055/s-0033-1354578 PubMedGoogle Scholar
  7. 7.
    K. Kiseljak-Vassiliades, N.E. Carlson, M.T. Borges, B.K. Kleinschmidt-DeMasters, K.O. Lillehei, J.M. Kerr, M.E. Wierman, Growth hormone tumor histological subtypes predict response to surgical and medical therapy. Endocrine 49(1), 231–241 (2015).  https://doi.org/10.1007/s12020-014-0383-y CrossRefPubMedGoogle Scholar
  8. 8.
    P.R. Mazal, T. Czech, R. Sedivy, M. Aichholzer, J. Wanschitz, N. Klupp, H. Budka, Prognostic relevance of intracytoplasmic cytokeratin pattern, hormone expression profile, and cell proliferation in pituitary adenomas of akromegalic patients. Clin. Neuropathol. 20(4), 163–171 (2001)PubMedGoogle Scholar
  9. 9.
    Y. Bakhtiar, H. Hirano, K. Arita, S. Yunoue, S. Fujio, A. Tominaga, T. Sakoguchi, K. Sugiyama, K. Kurisu, J. Yasufuku-Takano, K. Takano, Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae. Eur. J. Endocrinol. 163(4), 531–539 (2010).  https://doi.org/10.1530/EJE-10-0586 CrossRefPubMedGoogle Scholar
  10. 10.
    S. Ahmed, M. Elsheikh, I.M. Stratton, R.C. Page, C.B. Adams, J.A. Wass, Outcome of transphenoidal surgery for acromegaly and its relationship to surgical experience. Clin. Endocrinol. 50(5), 561–567 (1999)CrossRefGoogle Scholar
  11. 11.
    V. Briceno, H.A. Zaidi, J.A. Doucette, K.B. Onomichi, A. Alreshidi, R.A. Mekary, T.R. Smith, Efficacy of transsphenoidal surgery in achieving biochemical cure of growth hormone-secreting pituitary adenomas among patients with cavernous sinus invasion: a systematic review and meta-analysis. Neurol. Res 39(5), 387–398 (2017).  https://doi.org/10.1080/01616412.2017.1296653 CrossRefPubMedGoogle Scholar
  12. 12.
    C.C. van Bunderen, N.C. van Varsseveld, J.C. Baayen, W.R. van Furth, E.S. Aliaga, M.J. Hazewinkel, C.B. Majoie, N.J. Freling, P. Lips, E. Fliers, P.H. Bisschop, M.L. Drent, Predictors of endoscopic transsphenoidal surgery outcome in acromegaly: patient and tumor characteristics evaluated by magnetic resonance imaging. Pituitary 16(2), 158–167 (2013).  https://doi.org/10.1007/s11102-012-0395-7 CrossRefPubMedGoogle Scholar
  13. 13.
    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 52(2), 333–343 (2016).  https://doi.org/10.1007/s12020-015-0766-8 CrossRefPubMedGoogle Scholar
  14. 14.
    A. Heck, G. Ringstad, S.L. Fougner, O. Casar-Borota, T. Nome, J. Ramm-Pettersen, J. Bollerslev, Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly. Clin. Endocrinol. 77(1), 72–78 (2012).  https://doi.org/10.1111/j.1365-2265.2011.04286.x CrossRefGoogle Scholar
  15. 15.
    M. Shen, Q. Zhang, W. Liu, M. Wang, J. Zhu, Z. Ma, W. He, S. Li, X. Shou, Y. Li, Z. Zhang, H. Ye, M. He, B. Lu, Z. Yao, Y. Lu, N. Qiao, Z. Ye, Y. Zhang, Y. Yang, Y. Zhao, Y. Wang, Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly. Neuroradiology 58(11), 1057–1065 (2016).  https://doi.org/10.1007/s00234-016-1728-4 CrossRefPubMedGoogle Scholar
  16. 16.
    A.S. Micko, A. Wohrer, S. Wolfsberger, E. Knosp, Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification. J. Neurosurg. 122(4), 803–811 (2015).  https://doi.org/10.3171/2014.12.JNS141083 CrossRefPubMedGoogle Scholar
  17. 17.
    A. Obari, T. Sano, K. Ohyama, E. Kudo, Z.R. Qian, A. Yoneda, N. Rayhan, M. Mustafizur Rahman, S. Yamada, Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. Endocr. Pathol. 19(2), 82–91 (2008).  https://doi.org/10.1007/s12022-008-9029-z CrossRefPubMedGoogle Scholar
  18. 18.
    H. Nishioka, N. Fukuhara, K. Horiguchi, S. Yamada, Aggressive transsphenoidal resection of tumors invading the cavernous sinus in patients with acromegaly: predictive factors, strategies, and outcomes. J. Neurosurg. 121(3), 505–510 (2014).  https://doi.org/10.3171/2014.3.JNS132214 CrossRefPubMedGoogle Scholar
  19. 19.
    A.E. Yildirim, M. Sahinoglu, D. Divanlioglu, F. Alagoz, A.G. Gurcay, E. Daglioglu, H.O. Okay, A.D. Belen, Endoscopic endonasal transsphenoidal treatment for acromegaly: 2010 consensus criteria for remission and predictors of outcomes. Turk. Neurosurg. 24(6), 906–912 (2014).  https://doi.org/10.5137/1019-5149.JTN.11288-14.1 PubMedGoogle Scholar
  20. 20.
    A. Bourdelot, J. Coste, V. Hazebroucq, S. Gaillard, L. Cazabat, X. Bertagna, J. Bertherat, Clinical, hormonal and magnetic resonance imaging (MRI) predictors of transsphenoidal surgery outcome in acromegaly. Eur. J. Endocrinol. 150(6), 763–771 (2004)CrossRefPubMedGoogle Scholar
  21. 21.
    A. Abosch, J.B. Tyrrell, K.R. Lamborn, L.T. Hannegan, C.B. Applebury, C.B. Wilson, Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial outcome and long-term results. J. Clin. Endocrinol. Metab. 83(10), 3411–3418 (1998).  https://doi.org/10.1210/jcem.83.10.5111 CrossRefPubMedGoogle Scholar
  22. 22.
    D.B. Hazer, S. Isik, D. Berker, S. Guler, A. Gurlek, T. Yucel, M. Berker, 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).  https://doi.org/10.3171/2013.8.JNS13224 CrossRefPubMedGoogle Scholar
  23. 23.
    R.M. Starke, D.M. Raper, S.C. Payne, M.L. Vance, E.H. Oldfield, J.A. Jane Jr., Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J. Clin. Endocrinol. Metab. 98(8), 3190–3198 (2013).  https://doi.org/10.1210/jc.2013-1036 CrossRefPubMedGoogle Scholar
  24. 24.
    M. Shirvani, R. Motiei-Langroudi, Transsphenoidal surgery for growth hormone-secreting pituitary adenomas in 130 patients. World Neurosurg. 81(1), 125–130 (2014).  https://doi.org/10.1016/j.wneu.2013.01.021 CrossRefPubMedGoogle Scholar
  25. 25.
    J.A. Gondim, J.P. Almeida, L.A. de Albuquerque, E. Gomes, M. Schops, T. Ferraz, Pure endoscopic transsphenoidal surgery for treatment of acromegaly: results of 67 cases treated in a pituitary center. Neurosurg. Focus 29(4), E7 (2010).  https://doi.org/10.3171/2010.7.FOCUS10167 CrossRefPubMedGoogle Scholar
  26. 26.
    R. Attanasio, M. Montini, M. Valota, L. Cortesi, R. Barbo, F. Biroli, G. Tonnarelli, M. Albizzi, R.M. Testa, G. Pagani, An audit of treatment outcome in acromegalic patients attending our center at Bergamo, Italy. Pituitary 11(1), 1–11 (2008).  https://doi.org/10.1007/s11102-007-0059-1 CrossRefPubMedGoogle Scholar
  27. 27.
    I. Potorac, P. Petrossians, A.F. Daly, F. Schillo, C. Ben Slama, S. Nagi, M. Sahnoun, T. Brue, N. Girard, P. Chanson, G. Nasser, P. Caron, F. Bonneville, G. Raverot, V. Lapras, F. Cotton, B. Delemer, B. Higel, A. Boulin, S. Gaillard, F. Luca, B. Goichot, J.L. Dietemann, A. Beckers, J.F. Bonneville, Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences. Endocr. Relat. Cancer 22(2), 169–177 (2015).  https://doi.org/10.1530/ERC-14-0305 CrossRefPubMedGoogle Scholar
  28. 28.
    A. Hagiwara, Y. Inoue, K. Wakasa, T. Haba, T. Tashiro, T. Miyamoto, Comparison of growth hormone-producing and non-growth hormone-producing pituitary adenomas: imaging characteristics and pathologic correlation. Radiology 228(2), 533–538 (2003).  https://doi.org/10.1148/radiol.2282020695 CrossRefPubMedGoogle Scholar
  29. 29.
    M. Puig-Domingo, E. Resmini, B. Gomez-Anson, J. Nicolau, M. Mora, E. Palomera, C. Marti, I. Halperin, S.M. Webb, 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).  https://doi.org/10.1210/jc.2010-0573 CrossRefPubMedGoogle Scholar
  30. 30.
    H. Babu, A. Ortega, M. Nuno, A. Dehghan, A. Schweitzer, H.V. Bonert, J.D. Carmichael, O. Cooper, S. Melmed, A.N. Mamelak, Long-term endocrine outcomes following endoscopic endonasal transsphenoidal surgery for acromegaly and associated prognostic factors. Neurosurgery 81(2), 357–366 (2017).  https://doi.org/10.1093/neuros/nyx020 CrossRefPubMedGoogle Scholar
  31. 31.
    R.A. Feelders, M. Bidlingmaier, C.J. Strasburger, J.A. Janssen, P. Uitterlinden, L.J. Hofland, S.W. Lamberts, A.J. van der Lely, W.W. de Herder, Postoperative evaluation of patients with acromegaly: clinical significance and timing of oral glucose tolerance testing and measurement of (free) insulin-like growth factor I, acid-labile subunit, and growth hormone-binding protein levels. J. Clin. Endocrinol. Metab. 90(12), 6480–6489 (2005).  https://doi.org/10.1210/jc.2005-0901 CrossRefPubMedGoogle Scholar
  32. 32.
    P. Dutta, M. Korbonits, N. Sachdeva, P. Gupta, A. Srinivasan, J.S. Devgun, A. Bajaj, K.K. Mukherjee, Can immediate postoperative random growth hormone levels predict long-term cure in patients with acromegaly? Neurol. India 64(2), 252–258 (2016).  https://doi.org/10.4103/0028-3886.177622 CrossRefPubMedGoogle Scholar
  33. 33.
    S. Valdemarsson, S. Ljunggren, M. Bramnert, O. Norrhamn, C.H. Nordstrom, Early postoperative growth hormone levels: high predictive value for long-term outcome after surgery for acromegaly. J. Intern Med 247(6), 640–650 (2000)CrossRefPubMedGoogle Scholar
  34. 34.
    S. Sarkar, K.S. Jacob, R. Pratheesh, A.G. Chacko, Transsphenoidal surgery for acromegaly: predicting remission with early postoperative growth hormone assays. Acta Neurochir. 156(7), 1379–1387 (2014).  https://doi.org/10.1007/s00701-014-2098-5. discussion 1387CrossRefPubMedGoogle Scholar
  35. 35.
    E.H. Kim, M.C. Oh, E.J. Lee, S.H. Kim, Predicting long-term remission by measuring immediate postoperative growth hormone levels and oral glucose tolerance test in acromegaly. Neurosurgery 70(5), 1106–1113 (2012).  https://doi.org/10.1227/NEU.0b013e31823f5c16. discussion 1113CrossRefPubMedGoogle Scholar
  36. 36.
    M.D. Krieger, W.T. Couldwell, M.H. Weiss, Assessment of long-term remission of acromegaly following surgery. J. Neurosurg. 98(4), 719–724 (2003).  https://doi.org/10.3171/jns.2003.98.4.0719 CrossRefPubMedGoogle Scholar
  37. 37.
    J.H. Kim, K.Y. Hur, J.H. Lee, J.H. Lee, Y.B. Se, H.I. Kim, S.H. Lee, D.H. Nam, S.Y. Kim, K.W. Kim, D.S. Kong, Y.H. Kim, Outcome of endoscopic transsphenoidal surgery for acromegaly. World Neurosurg. 104, 272–278 (2017).  https://doi.org/10.1016/j.wneu.2017.04.141 CrossRefPubMedGoogle Scholar
  38. 38.
    J. Kreutzer, M.L. Vance, M.B. Lopes, E.R. Laws Jr., Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. J. Clin. Endocrinol. Metab. 86(9), 4072–4077 (2001).  https://doi.org/10.1210/jcem.86.9.7819 CrossRefPubMedGoogle Scholar
  39. 39.
    M. Yu, D.E. Bruns, J.A. Jane Jr., R.M. Nass, E.H. Oldfield, M.L. Vance, M.O. Thorner, Decrease of serum IGF-I following transsphenoidal pituitary surgery for acromegaly. Clin. Chem. 63(2), 486–494 (2017).  https://doi.org/10.1373/clinchem.2016.262592 CrossRefPubMedGoogle Scholar
  40. 40.
    J.A. Takahashi, A. Shimatsu, K. Nakao, N. Hashimoto, Early postoperative indicators of late outcome in acromegalic patients. Clin. Endocrinol. 60(3), 366–374 (2004)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ximene Antunes
    • 1
  • Nina Ventura
    • 2
  • Gustavo Bittencourt Camilo
    • 3
  • Luiz Eduardo Wildemberg
    • 1
    • 4
  • Andre Guasti
    • 5
  • Paulo José M. Pereira
    • 5
  • Aline Helen Silva Camacho
    • 6
    • 7
  • Leila Chimelli
    • 6
  • Paulo Niemeyer
    • 5
  • Mônica R. Gadelha
    • 1
    • 4
  • Leandro Kasuki
    • 1
    • 4
    • 8
  1. 1.Neuroendocrinology Research Center / Endocrinology Division – Medical School and Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Radiology Division - Instituto Estadual do Cérebro Paulo NiemeyerRio de JaneiroBrazil
  3. 3.Radiology Division - Instituição Hospital e Maternidade Terezinha de Jesus -Juiz de ForaMinas GeraisBrazil
  4. 4.Neuroendocrinology Division – Instituto Estadual do Cérebro Paulo NiemeyerRio de JaneiroBrazil
  5. 5.Neurosurgery Division – Instituto Estadual do Cérebro Paulo NiemeyerRio de JaneiroBrazil
  6. 6.Neuropathology and Molecular Genetics Laboratory – Instituto Estadual do Cérebro Paulo NiemeyerRio de JaneiroBrazil
  7. 7.Pathology Division – Instituto Nacional do CâncerRio de JaneiroBrazil
  8. 8.Endocrinology Division – Hospital Federal de BonsucessoRio de JaneiroBrazil

Personalised recommendations