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Magnetic resonance spectroscopy may serve as a presurgical predictor of somatostatin analog therapy response in patients with growth hormone-secreting pituitary macroadenomas

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Abstract

Purpose

Somatostatin analogs (SSAs) are considered one of the most effective medical treatments for patients with growth hormone-secreting pituitary adenomas (GH-PAs). The postoperative electron microscopy (EM) pathological subtype and SSTR2 expression in the tumor are the most established predictors of patient response to SSA therapy. The aim of this study was to evaluate how will magnetic resonance spectroscopy (MRS) measurements before surgery predict the EM pathological subtypes and SSTR2 expression of tumors, and thereby serve as an indicator for the therapeutic sensitivity to SSAs of patients with GH-PAs.

Methods

Eighteen patients with GH pituitary macroadenomas who underwent transsphenoidal surgery were included in this retrospective study. The preoperative MRS data and T2 signal intensity were obtained from patients by 1.5 T MR spectroscopy of the sellar mass. The EM pathological subtypes of tumors were determined after surgery through examination of cell granulations. The expressions of somatostatin receptor 2 (SSTR2), SSTR5, P21, P27, and Ki-67 were evaluated by immunohistochemistry.

Results

The MRS parameters that were found to significantly predict the EM pathological subtypes of tumors, as calculated by the receiver operating characteristic curve, were the choline (Ch) value at 3140.5 MR units (sensitivity 69.2%, specificity 100%) and the choline/creatine (Ch/Cr) ratio at 1.27 (sensitivity 92.3%, specificity 100%). Further, the Ch/Cr ratio, but not other MRS data, was shown to negatively correlate with the expression of SSTR2 (P = 0.02). The Ch/Cr ratio was also found to positively correlate with the Ki-67 value (P < 0.05) and T2 signal (P < 0.05), but not with other factors that were examined in this study. Moreover, the Ch/Cr ratio could predict the EM pathological subtypes of tumors with an accuracy of 83.3% (5/6) for patients with an isointense T2 signal.

Conclusion

The Ch/Cr ratio by MRS could effectively predict the tumor subtype and was significantly correlated with the expression of SSTR2, which was consistent with other predictors. It was also able to distinguish the patients with isointense T2 signals. Our results provide a potentially new and non-invasive method to predict the response to SSAs in patients with GH pituitary macroadenomas.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (no. 81528014) and New Clinical Technology Project of Xinqiao Hospital (no. 2015LCXJS034). The authors sincerely thank Prof. Qinglai Yang (Department of Microbiology and Immunology, Emory University School of Medicine) for helping to proofread for language and to format the manuscript.

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Authors and Affiliations

  1. Multidisciplinary Center for Pituitary Adenomas of Chongqing, Chongqing, 400037, China

    J. Hu, J. Yan, X. Zheng, Y. Zhang, Q. Ran, X. Tang, T. Shu, R. Shen, L. Duan, D. Zhang, Q. Guo, H. Yang & S. Li

  2. Department of Neurosurgery, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China

    J. Hu, J. Yan, X. Zheng, Y. Zhang, H. Yang & S. Li

  3. Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China

    Q. Ran, T. Shu & D. Zhang

  4. Department of Pathology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China

    X. Tang & Q. Guo

  5. Department of Endocrinology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China

    R. Shen & L. Duan

  6. Department of Biology and Biochemistry, University of Houston, Houston, TX, USA

    W. Zhang

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  1. J. Hu
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The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical standards

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

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

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40618_2018_939_MOESM1_ESM.tif

Supplemental Figure 1. The schematic images of 1H-MRSI data. Green point represent area of GH adenoma(A) and temporal lobe as self control(B). C: Oscillogram of 1H-MRSI, CH, choline-containing compound, value 6369; Cr, creatine, value 1969; NAA, N-acetylaspartate, value 816. D and E: The T2 intensity of GH-PAs hypointense and hyperintense respectively. F: Sagittal view was used to calculate tumor volume and help to locate the green point used in A and B (TIFF 2985 kb)

40618_2018_939_MOESM2_ESM.tif

Supplemental Figure 2. The ultrastructure of GH adenoma cells under electronic microscope. A: Densely granulated (DG), GH tumor with a large number of spherical secretory granules, the longest diameter varies between 300-600 nm (×8900). B: Sparsely granulated (SG), GH tumors with fibrous bodies and reduced size and number of secretory granules, the majority diameter were measured only 100-250 nm (×8900) (TIFF 2079 kb)

40618_2018_939_MOESM3_ESM.tif

Supplemental Figure 3. Immunohistochemical expression of SSTR2, SSTR5, P27 and P21 in GH-PAs. Representative examples of low—IRS(1-3), medium—IRS(4-9), and high—IRS(9-12) are demonstrated (magnification,×400) (TIFF 3462 kb)

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Hu, J., Yan, J., Zheng, X. et al. Magnetic resonance spectroscopy may serve as a presurgical predictor of somatostatin analog therapy response in patients with growth hormone-secreting pituitary macroadenomas. J Endocrinol Invest 42, 443–451 (2019). https://doi.org/10.1007/s40618-018-0939-4

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