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Neuroradiology

, Volume 58, Issue 11, pp 1057–1065 | Cite as

Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly

  • Ming Shen
  • Qilin Zhang
  • Wenjuan Liu
  • Meng Wang
  • Jingjing Zhu
  • Zengyi Ma
  • Wenqiang He
  • Shiqi Li
  • Xuefei Shou
  • Yiming Li
  • Zhaoyun Zhang
  • Hongying Ye
  • Min He
  • Bin Lu
  • Zhenwei Yao
  • Yun Lu
  • Nidan Qiao
  • Zhao Ye
  • Yichao Zhang
  • Yeping Yang
  • Yao ZhaoEmail author
  • Yongfei WangEmail author
Diagnostic Neuroradiology

Abstract

Introduction

The difficulty of predicting the efficacy of somatostatin analogs (SSA) is not fully resolved. Here, we quantitatively evaluated the predictive value of relative signal intensity (rSI) on T1- and T2-weighted magnetic resonance imaging (MRI) for the short-term efficacy (3 months) of SSA therapy in patients with active acromegaly and assessed the correlation between MRI rSI and expression of somatostatin receptors (SSTR).

Methods

This was a retrospective review of prospectively recorded data. Ninety-two newly diagnosed patients (37 males and 55 females) with active acromegaly were recruited. All patients were treated with pre-surgical SSA, followed by reassessment and transspenoidal surgery. rSI values were generated by calculating the ratio of SI in the tumor to the SI of normal frontal white matter. The Youden indices were calculated to determine the optimal cutoff of rSI to determine the efficacy of SSA. The correlation between rSI and expression of SSTR2/5 was analyzed by the Spearman rank correlation coefficient.

Results

T2 rSI was strongly correlated with biochemical sensitivity to SSA. The cutoff value of T2 rSI to distinguish biochemical sensitivity was 1.205, with a positive predictive value (PPV) of 81.5 % and a negative predictive value (NPV) of 77.3 %. No correlation was found between MRI and tumor size sensitivity. Moreover, T2 rSI was negatively correlated with the expression of SSTR5.

Conclusion

T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly.

Keywords

Acromegaly Magnetic resonance imaging Relative signal intensity Somatostatin analog Somatostatin receptor 

Notes

Acknowledgments

This study was supported by grants from the National High Technology Research and Development Program of China (No. 2014AA02061), the National Program for Support of Top-Notch Young Professionals, the National Natural Science Foundation of China (No. 81172391, No. 81370938, No. 81370884), the Program for New Century Excellent Talents in University (NCET-10-0356), the Shanghai Rising-Star Tracking Program (12QH1400400), the China Pituitary Adenoma Specialist Council (CPASC), the Shanghai Science and Technology Committee (11PJ1402000) and the Shanghai Municipal Commission of Health and Family Planning (XYQ2011002, XYQ2013120).

Compliance with ethical standards

We declare that all human and animal studies have been approved by the ethics committee at Huashan Hospital and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We declare that all patients gave informed consent prior to inclusion in this study.

Conflict of interest

We declare that we have no conflict of interest.

Supplementary material

234_2016_1728_MOESM1_ESM.xlsx (13 kb)
ESM 1 (XLSX 13 kb)
234_2016_1728_MOESM2_ESM.docx (16 kb)
Supplementary Table 1 (DOCX 15 kb)

References

  1. 1.
    Katznelson L, Atkinson JL, Cook DM, Ezzat SZ, Hamrahian AH, Miller KK, American Association of Clinical E (2011) American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly--2011 update. Endocr Pract 17(Suppl 4):1–44CrossRefPubMedGoogle Scholar
  2. 2.
    Melmed S (2009) Acromegaly pathogenesis and treatment. J Clin Invest 119(11):3189–3202. doi: 10.1172/JCI39375 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Melmed S, Jackson I, Kleinberg D, Klibanski A (1998) Current treatment guidelines for acromegaly. J Clin Endocrinol Metab 83(8):2646–2652. doi: 10.1210/jcem.83.8.4995 PubMedGoogle Scholar
  4. 4.
    Colao A, Auriemma RS, Lombardi G, Pivonello R (2011) Resistance to somatostatin analogs in acromegaly. Endocr Rev 32(2):247–271. doi: 10.1210/er.2010-0002 CrossRefPubMedGoogle Scholar
  5. 5.
    Park C, Yang I, Woo J, Kim S, Kim J, Kim Y, Sohn S, Kim E, Lee M, Park H, Jung J, Park S (2004) Somatostatin (SRIF) receptor subtype 2 and 5 gene expression in growth hormone-secreting pituitary adenomas: the relationship with endogenous srif activity and response to octreotide. Endocr J 51(2):227–236CrossRefPubMedGoogle Scholar
  6. 6.
    Taboada GF, Luque RM, Bastos W, Guimaraes RF, Marcondes JB, Chimelli LM, Fontes R, Mata PJ, Filho PN, Carvalho DP, Kineman RD, Gadelha MR (2007) Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas. Eur J Endocrinol 156(1):65–74. doi: 10.1530/eje.1.02313 CrossRefPubMedGoogle Scholar
  7. 7.
    Fougner SL, Casar-Borota O, Heck A, Berg JP, Bollerslev J (2012) 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. doi: 10.1111/j.1365-2265.2011.04163.x CrossRefGoogle Scholar
  8. 8.
    Bhayana S, Booth GL, Asa SL, Kovacs K, Ezzat S (2005) The implication of somatotroph adenoma phenotype to somatostatin analog responsiveness in acromegaly. J Clin Endocrinol Metab 90(11):6290–6295. doi: 10.1210/jc.2005-0998 CrossRefPubMedGoogle Scholar
  9. 9.
    Jenkins PJ, Emery M, Howling SJ, Evanson J, Besser GM, Monson JP (2004) Predicting therapeutic response and degree of pituitary tumour shrinkage during treatment of acromegaly with octreotide LAR. Horm Res 62(5):227–232. doi: 10.1159/000081418 PubMedGoogle Scholar
  10. 10.
    Biermasz NR, Pereira AM, Smit JW, Romijn JA, Roelfsema F (2005) Intravenous octreotide test predicts the long term outcome of treatment with octreotide-long-acting repeatable in active acromegaly. Growth Hormon IGF Res 15(3):200–206. doi: 10.1016/j.ghir.2005.02.007 CrossRefGoogle Scholar
  11. 11.
    Puig-Domingo M, Resmini E, Gomez-Anson B, Nicolau J, Mora M, Palomera E, Marti C, Halperin I, Webb SM (2010) Magnetic resonance imaging as a predictor of response to somatostatin analogs in acromegaly after surgical failure. J Clin Endocrinol Metab 95(11):4973–4978. doi: 10.1210/jc.2010-0573 CrossRefPubMedGoogle Scholar
  12. 12.
    Heck A, Ringstad G, Fougner SL, Casar-Borota O, Nome T, Ramm-Pettersen J, Bollerslev J (2012) 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. doi: 10.1111/j.1365-2265.2011.04286.x CrossRefGoogle Scholar
  13. 13.
    Pokrajac A, Claridge AG, Shakoor SK, Trainer PJ (2006) The octreotide test dose is not a reliable predictor of the subsequent response to somatostatin analogue therapy in patients with acromegaly. Eur J Endocrinol 154(2):267–274. doi: 10.1530/eje.1.02073 CrossRefPubMedGoogle Scholar
  14. 14.
    Heck A, Emblem KE, Casar-Borota O, Bollerslev J, Ringstad G (2016) Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly. Endocrine 52(2):333–343. doi: 10.1007/s12020-015-0766-8 CrossRefPubMedGoogle Scholar
  15. 15.
    Di Chiro G, Nelson KB (1962) The volume of the sella turcica. Am J Roentgenol Radium Therapy Nucl Med 87:989–1008Google Scholar
  16. 16.
    Ma Z, He W, Zhao Y, Yuan J, Zhang Q, Wu Y, Chen H, Yao Z, Li S, Wang Y (2015) Predictive value of PWI for blood supply and T1-spin echo MRI for consistency of pituitary adenoma. Neuroradiology. doi: 10.1007/s00234-015-1591-8 Google Scholar
  17. 17.
    Bala A, Lojek E, Marchel A (2015) Cognitive functioning of patients with a PRL-secreting pituitary adenoma: a preliminary report. Neurology. doi: 10.1212/WNL.0000000000002252 PubMedGoogle Scholar
  18. 18.
    Abosch A, Tyrrell JB, Lamborn KR, Hannegan LT, Applebury CB, Wilson CB (1998) Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial outcome and long-term results. J Clin Endocrinol Metab 83(10):3411–3418. doi: 10.1210/jcem.83.10.5111 CrossRefPubMedGoogle Scholar
  19. 19.
    Bates AS, Van’t Hoff W, Jones JM, Clayton RN (1993) An audit of outcome of treatment in acromegaly. Q J Med 86(5):293–299PubMedGoogle Scholar
  20. 20.
    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, Acromegaly Consensus G (2009) Guidelines for acromegaly management: an update. J Clin Endocrinol Metab 94(5):1509–1517. doi: 10.1210/jc.2008-2421 CrossRefPubMedGoogle Scholar
  21. 21.
    Fougner SL, Bollerslev J, Svartberg J, Oksnes M, Cooper J, Carlsen SM (2014) Preoperative octreotide treatment of acromegaly: long-term results of a randomised controlled trial. Eur J Endocrinol 171(2):229–235. doi: 10.1530/EJE-14-0249 CrossRefPubMedGoogle Scholar
  22. 22.
    Shen M, Shou X, Wang Y, Zhang Z, Wu J, Mao Y, Li S, Zhao Y (2010) Effect of presurgical long-acting octreotide treatment in acromegaly patients with invasive pituitary macroadenomas: a prospective randomized study. Endocr J 57(12):1035–1044CrossRefPubMedGoogle Scholar
  23. 23.
    Taboada GF, Luque RM, Neto LV, Machado Ede O, Sbaffi BC, Domingues RC, Marcondes JB, Chimelli LM, Fontes R, Niemeyer P, de Carvalho DP, Kineman RD, Gadelha MR (2008) Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. Eur J Endocrinol 158(3):295–303. doi: 10.1530/EJE-07-0562 CrossRefPubMedGoogle Scholar
  24. 24.
    Gadelha MR, Kasuki L, Korbonits M (2013) Novel pathway for somatostatin analogs in patients with acromegaly. Trends Endocrinol Metab 24(5):238–246. doi: 10.1016/j.tem.2012.11.007 CrossRefPubMedGoogle Scholar
  25. 25.
    Potorac I, Petrossians P, Daly AF, Schillo F, Ben Slama C, Nagi S, Sahnoun M, Brue T, Girard N, Chanson P, Nasser G, Caron P, Bonneville F, Raverot G, Lapras V, Cotton F, Delemer B, Higel B, Boulin A, Gaillard S, Luca F, Goichot B, Dietemann JL, Beckers A, Bonneville JF (2015) Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences. Endocr Relat Cancer 22(2):169–177. doi: 10.1530/ERC-14-0305 CrossRefPubMedGoogle Scholar
  26. 26.
    Bourdelot A, Coste J, Hazebroucq V, Gaillard S, Cazabat L, Bertagna X, Bertherat J (2004) Clinical, hormonal and magnetic resonance imaging (MRI) predictors of transsphenoidal surgery outcome in acromegaly. Eur J Endocrinol 150(6):763–771CrossRefPubMedGoogle Scholar
  27. 27.
    Cozzi R, Montini M, Attanasio R, Albizzi M, Lasio G, Lodrini S, Doneda P, Cortesi L, Pagani G (2006) Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage. J Clin Endocrinol Metab 91(4):1397–1403. doi: 10.1210/jc.2005-2347 CrossRefPubMedGoogle Scholar
  28. 28.
    Guler HP, Zapf J, Schmid C, Froesch ER (1989) Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates. Acta Endocrinol (Copenh) 121(6):753–758Google Scholar
  29. 29.
    Heck A, Emblem KE, Casar-Borota O, Bollerslev J, Ringstad G (2015) Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly. Endocrine. doi: 10.1007/s12020-015-0766-8 Google Scholar
  30. 30.
    Pierallini A, Caramia F, Falcone C, Tinelli E, Paonessa A, Ciddio AB, Fiorelli M, Bianco F, Natalizi S, Ferrante L, Bozzao L (2006) Pituitary macroadenomas: preoperative evaluation of consistency with diffusion-weighted MR imaging--initial experience. Radiology 239(1):223–231. doi: 10.1148/radiol.2383042204 CrossRefPubMedGoogle Scholar
  31. 31.
    Mahmoud OM, Tominaga A, Amatya VJ, Ohtaki M, Sugiyama K, Sakoguchi T, Kinoshita Y, Takeshima Y, Abe N, Akiyama Y, El-Ghoriany AI, Abd Alla AK, El-Sharkawy MA, Arita K, Kurisu K, Yamasaki F (2011) Role of PROPELLER diffusion-weighted imaging and apparent diffusion coefficient in the evaluation of pituitary adenomas. Eur J Radiol 80(2):412–417. doi: 10.1016/j.ejrad.2010.05.023 CrossRefPubMedGoogle Scholar
  32. 32.
    Patel YC (1999) Somatostatin and its receptor family. Front Neuroendocrinol 20(3):157–198. doi: 10.1006/frne.1999.0183 CrossRefPubMedGoogle Scholar
  33. 33.
    Giustina A, Karamouzis I, Patelli I, Mazziotti G (2013) Octreotide for acromegaly treatment: a reappraisal. Expert Opin Pharmacother 14(17):2433–2447. doi: 10.1517/14656566.2013.847090 CrossRefPubMedGoogle Scholar
  34. 34.
    Kato M, Inoshita N, Sugiyama T, Tani Y, Shichiri M, Sano T, Yamada S, Hirata Y (2012) Differential expression of genes related to drug responsiveness between sparsely and densely granulated somatotroph adenomas. Endocr J 59(3):221–228CrossRefPubMedGoogle Scholar
  35. 35.
    Mayr B, Buslei R, Theodoropoulou M, Stalla GK, Buchfelder M, Schofl C (2013) Molecular and functional properties of densely and sparsely granulated GH-producing pituitary adenomas. Eur J Endocrinol 169(4):391–400. doi: 10.1530/EJE-13-0134 CrossRefPubMedGoogle Scholar
  36. 36.
    Gatto F, Feelders RA, van der Pas R, Kros JM, Waaijers M, Sprij-Mooij D, Neggers SJ, van der Lelij AJ, Minuto F, Lamberts SW, de Herder WW, Ferone D, Hofland LJ (2013) Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly. J Clin Endocrinol Metab 98(1):E66–E71. doi: 10.1210/jc.2012-2609 CrossRefPubMedGoogle Scholar
  37. 37.
    Casar-Borota O, Heck A, Schulz S, Nesland JM, Ramm-Pettersen J, Lekva T, Alafuzoff I, Bollerslev J (2013) 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. doi: 10.1210/jc.2013-2145 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Ming Shen
    • 1
    • 2
  • Qilin Zhang
    • 1
    • 2
  • Wenjuan Liu
    • 2
    • 3
  • Meng Wang
    • 3
    • 4
  • Jingjing Zhu
    • 2
    • 5
  • Zengyi Ma
    • 1
    • 2
  • Wenqiang He
    • 1
    • 2
  • Shiqi Li
    • 1
    • 2
  • Xuefei Shou
    • 1
    • 2
  • Yiming Li
    • 2
    • 3
  • Zhaoyun Zhang
    • 2
    • 3
  • Hongying Ye
    • 2
    • 3
  • Min He
    • 2
    • 3
  • Bin Lu
    • 2
    • 3
  • Zhenwei Yao
    • 2
    • 6
  • Yun Lu
    • 7
  • Nidan Qiao
    • 1
    • 2
  • Zhao Ye
    • 1
    • 2
  • Yichao Zhang
    • 1
    • 2
  • Yeping Yang
    • 2
    • 3
  • Yao Zhao
    • 1
    • 2
    Email author
  • Yongfei Wang
    • 1
    • 2
    Email author
  1. 1.Department of Neurosurgery, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina
  2. 2.Shanghai Pituitary Tumor CenterShanghaiChina
  3. 3.Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina
  4. 4.Division of Endocrinology, the Second Affiliated HospitalSoochow UniversitySuzhouChina
  5. 5.Department of Neuropathology, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina
  6. 6.Department of Radiology, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina
  7. 7.Department of Nuclear Medicine, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina

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