Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly
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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).
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.
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.
T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly.
KeywordsAcromegaly Magnetic resonance imaging Relative signal intensity Somatostatin analog Somatostatin receptor
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.
- 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
- 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.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.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
- 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.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
- 15.Di Chiro G, Nelson KB (1962) The volume of the sella turcica. Am J Roentgenol Radium Therapy Nucl Med 87:989–1008Google Scholar
- 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
- 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
- 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
- 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.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
- 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.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
- 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.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