, Volume 52, Issue 2, pp 333–343 | Cite as

Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly

  • Ansgar Heck
  • Kyrre E. Emblem
  • Olivera Casar-Borota
  • Jens Bollerslev
  • Geir Ringstad
Original Article


In growth hormone (GH)-producing adenomas, T2-weighted MRI signal intensity is a marker for granulation pattern and response to somatostatin analogs (SSA). Prediction of treatment response is necessary for individualized treatment, and T2 intensity assessment might improve preoperative classification of somatotropinomas. The objectives of this study are (I) to explore the feasibility of quantitative T2-weighted MRI histogram analyses in newly diagnosed somatotroph adenomas and their relation to clinical and histological parameters and (II) to compare the quantitative method to conventional, visual assessment of T2 intensity. The study was a retrospective cohort study of 58 newly diagnosed patients. In 34 of these, response to primary SSA treatment after median 6 months was evaluated. Parameters from the T2 histogram analyses (T2 intensity ratio and T2 homogeneity ratio) were correlated to visually assessed T2 intensity (hypo-, iso-, hyperintense), baseline characteristics, response to SSA treatment, and histological granulation pattern (anti-Cam5.2). T2 intensity ratio was lowest in the hypointense tumors and highest in the hyperintense tumors (0.66 ± 0.10 vs. 1.07 ± 0.11; p < 0.001). T2 intensity at baseline correlated with reduction in GH (r = −0.67; p < 0.001) and IGF-1 (r = −0.36; p = 0.037) after primary SSA treatment (n = 34). The T2 homogeneity ratio correlated with adenoma size reduction (r = −0.45; p = 0.008). Sparsely granulated adenomas had a higher T2 intensity than densely or intermediately granulated adenomas. T2 histogram analyses are an applicable tool to assess T2 intensity in somatotroph adenomas. Quantitatively assessed T2 intensity ratio in GH-producing adenomas correlates with conventional assessment of T2 intensity, baseline characteristics, response to SSA treatment, and histological granulation pattern.


Acromegaly T2 MRI Somatostatin analog Granulation 


Compliance with ethical standards

Conflict of interest

AH has received speaker fees from Novartis, Ipsen, NovoNordisk, and Pfizer and participated in Novartis’ nordic advisory board. KEE has intellectual property rights at NordicNeuroLab AS. JB has received an unrestricted research Grant from Novartis, Pfizer, and Merck Norway AS. The other authors have nothing to disclose.


  1. 1.
    S. Melmed, A. Colao, A. Barkan, M. Molitch, A.B. Grossman, D. Kleinberg, D. Clemmons, P. Chanson, E. Laws, J. Schlechte, M.L. Vance, K. Ho, A. Giustina, Acromegaly Consensus Group: guidelines for acromegaly management: an update. J. Clin. Endocrinol. Metab. 94(5), 1509–1517 (2009). doi: 10.1210/jc.2008-2421 CrossRefPubMedGoogle Scholar
  2. 2.
    A. Giustina, P. Chanson, D. Kleinberg, M.D. Bronstein, D.R. Clemmons, A. Klibanski, A.J. van der Lely, C.J. Strasburger, S.W. Lamberts, K.K.Y. Ho, F.F. Casanueva, S. Melmed, 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
  3. 3.
    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). doi: 10.1210/jc.2014-2700 CrossRefPubMedGoogle Scholar
  4. 4.
    S.M. Carlsen, M. Lund-Johansen, T. Schreiner, S. Aanderud, O. Johannesen, J. Svartberg, J.G. Cooper, J.K. Hald, S.L. Fougner, J. Bollerslev, Preoperative Octreotide Treatment of Acromegaly study group: 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
  5. 5.
    Z.-G. Mao, Y.-H. Zhu, H.-L. Tang, D.-Y. Wang, J. Zhou, D.-S. He, H. Lan, B.-N. Luo, H.-J. Wang, 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
  6. 6.
    M. Shen, X. Shou, Y. Wang, Z. Zhang, J. Wu, Y. Mao, S. Li, Y. Zhao, 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
  7. 7.
    S. Bacigaluppi, F. Gatto, P. Anania, N.L. Bragazzi, D.C. Rossi, G. Benvegnu, E. Nazzari, R. Spaziante, M. Giusti, D. Ferone, G. Zona, 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
  8. 8.
    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. (2014). doi: 10.1016/j.braindev.2014.04.009 Google Scholar
  9. 9.
    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
  10. 10.
    S.M. Carlsen, J. Svartberg, T. Schreiner, S. Aanderud, O. Johannesen, S. Skeie, M. Lund-Johansen, S.L. Fougner, J. Bollerslev, Preoperative Octreotide Treatment of Acromegaly study group: six-month preoperative octreotide treatment in unselected, de novo patients with acromegaly: effect on biochemistry, tumour volume, and postoperative cure. Clin. Endocrinol. 74(6), 736–743 (2011). doi: 10.1111/j.1365-2265.2011.03982.x CrossRefGoogle Scholar
  11. 11.
    A. Colao, R.S. Auriemma, G. Lombardi, R. Pivonello, Resistance to somatostatin analogs in acromegaly. Endocr. Rev. 32(2), 247–271 (2011). doi: 10.1210/er.2010-0002 CrossRefPubMedGoogle Scholar
  12. 12.
    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. 76(1), 96–102 (2012). doi: 10.1111/j.1365-2265.2011.04163.x CrossRefGoogle Scholar
  13. 13.
    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). doi: 10.1148/radiol.2282020695 CrossRefPubMedGoogle Scholar
  14. 14.
    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). doi: 10.1210/jc.2010-0573 CrossRefPubMedGoogle Scholar
  15. 15.
    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). doi: 10.1111/j.1365-2265.2011.04286.x CrossRefGoogle Scholar
  16. 16.
    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). doi: 10.1530/ERC-14-0305 CrossRefPubMedGoogle Scholar
  17. 17.
    K.E. Emblem, B. Nedregaard, T. Nome, P. Due-Tonnessen, J.K. Hald, D. Scheie, O.C. Borota, M. Cvancarova, A. Bjornerud, Glioma grading by using histogram analysis of blood volume heterogeneity from MR-derived cerebral blood volume maps. Radiology 247(3), 808–817 (2008). doi: 10.1148/radiol.2473070571 CrossRefPubMedGoogle Scholar
  18. 18.
    W.B. Pope, X.J. Qiao, H.J. Kim, A. Lai, P. Nghiemphu, X. Xue, B.M. Ellingson, D. Schiff, D. Aregawi, S. Cha, V.K. Puduvalli, J. Wu, W.K. Yung, G.S. Young, J. Vredenburgh, D. Barboriak, L.E. Abrey, T. Mikkelsen, R. Jain, N.A. Paleologos, P.L. Rn, M. Prados, J. Goldin, P.Y. Wen, T. Cloughesy, Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study. J. Neurooncol. 108(3), 491–498 (2012). doi: 10.1007/s11060-012-0847-y CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    S. Melmed, F.F. Casanueva, F. Cavagnini, P. Chanson, L. Frohman, A. Grossman, K. Ho, D. Kleinberg, S. Lamberts, E. Laws, G. Lombardi, M.L. Vance, K.V. Werder, J. Wass, A. Giustina, Acromegaly treatment consensus workshop participants: guidelines for acromegaly management. J. Clin. Endocrinol. Metab. 87(9), 4054–4058 (2002)CrossRefPubMedGoogle Scholar
  20. 20.
    D. Ferone, W.W. de Herder, R. Pivonello, J.M. Kros, P.M. van Koetsveld, T. de Jong, F. Minuto, A. Colao, S.W.J. Lamberts, L.J. Hofland, Correlation of in vitro and in vivo somatotropic adenoma responsiveness to somatostatin analogs and dopamine agonists with immunohistochemical evaluation of somatostatin and dopamine receptors and electron microscopy. J. Clin. Endocrinol. Metab. 93(4), 1412–1417 (2008). doi: 10.1210/jc.2007-1358 CrossRefPubMedGoogle Scholar
  21. 21.
    P.J. Caron, J.S. Bevan, S. Petersenn, D. Flanagan, A. Tabarin, G. Prevost, P. Maisonobe, A. Clermont, P. Investigators, Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J. Clin. Endocrinol. Metab. 99(4), 1282–1290 (2014). doi: 10.1210/jc.2013-3318 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    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). doi: 10.1007/s12022-008-9029-z CrossRefPubMedGoogle Scholar
  23. 23.
    P. Lundin, F. Pedersen, Volume of pituitary macroadenomas - assessment by MRI. J. Comput. Assist. Tomogr. 16(4), 519–528 (1992). doi: 10.1097/00004728-199207000-00004 CrossRefPubMedGoogle Scholar
  24. 24.
    A.L. Edal, K. Skjodt, H.J. Nepper-Rasmussen, SIPAP–a new MR classification for pituitary adenomas. Suprasellar, infrasellar, parasellar, anterior and posterior. Acta Radiol. 38(1), 30–36 (1997)CrossRefPubMedGoogle Scholar
  25. 25.
    E. Knosp, E. Steiner, K. Kitz, C. Matula, Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33(4), 610–617 (1993); discussion 617–618 CrossRefPubMedGoogle Scholar
  26. 26.
    J.F. Bonneville, F. Bonneville, F. Cattin, Magnetic resonance imaging of pituitary adenomas. Eur. Radiol. 15(3), 543–548 (2005). doi: 10.1007/s00330-004-2531-x CrossRefPubMedGoogle Scholar
  27. 27.
    A. Giustina, R. Berardelli, C. Gazzaruso, G. Mazziotti, Insulin and GH-IGF-I axis: endocrine pacer or endocrine disruptor? Acta Diabetol. (2014). doi: 10.1007/s00592-014-0635-6 PubMedGoogle Scholar
  28. 28.
    N.C. Olarescu, A. Heck, K. Godang, T. Ueland, J. Bollerslev, The metabolic risk in newly diagnosed patients with acromegaly is related to fat distribution and circulating adipokines and improves after treatment. Neuroendocrinology (2015). doi: 10.1159/000371818 PubMedGoogle Scholar
  29. 29.
    S. Bhayana, G.L. Booth, S.L. Asa, K. Kovacs, S. Ezzat, The implication of somatotroph adenoma phenotype to somatostatin analog responsiveness in acromegaly. J. Clin. Endocrinol. Metab. 90(11), 6290–6295 (2005). doi: 10.1210/jc.2005-0998 CrossRefPubMedGoogle Scholar
  30. 30.
    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). doi: 10.1007/s12020-014-0383-y CrossRefPubMedGoogle Scholar
  31. 31.
    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). doi: 10.1530/EJE-10-0586 CrossRefPubMedGoogle Scholar
  32. 32.
    S. Yamada, T. Aiba, T. Sano, K. Kovacs, Y. Shishiba, S. Sawano, K. Takada, Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology. Neurosurgery 33(1), 20–27 (1993)CrossRefPubMedGoogle Scholar
  33. 33.
    P. Boulby, T2: the transverse relaxation time, in Quantitative MRI of the brain—measuring changes caused by disease, vol. 1, ed. by P. Tofts (Wiley, Chichester, 2004), pp. 143–201Google Scholar
  34. 34.
    A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva, P. Trainer, E. Ghigo, K. Ho, S. Melmed, G. Acromegaly Consensus, 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

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Ansgar Heck
    • 1
    • 2
  • Kyrre E. Emblem
    • 3
  • Olivera Casar-Borota
    • 4
    • 5
  • Jens Bollerslev
    • 1
    • 2
  • Geir Ringstad
    • 6
  1. 1.Section of Specialized Endocrinology, Department of EndocrinologyOslo University Hospital, RikshospitaletOsloNorway
  2. 2.Faculty of MedicineUniversity of OsloOsloNorway
  3. 3.The Intervention CentreOslo University Hospital, RikshospitaletOsloNorway
  4. 4.Department of Immunology, Genetics and PathologyUppsala UniversityUppsalaSweden
  5. 5.Department of PathologyOslo University HospitalOsloNorway
  6. 6.Department of Radiology and Nuclear MedicineOslo University Hospital, RikshospitaletOsloNorway

Personalised recommendations