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. 2019 Apr;42(4):443-451. doi: 10.1007/s40618-018-0939-4. Epub 2018 Aug 31.

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.

Keywords: Granulation; Growth hormone-secreting pituitary adenomas; Proton magnetic resonance spectroscopic imaging; Somatostatin receptor subtype 2.

MeSH terms

  • Adenoma / drug therapy
  • Adenoma / metabolism
  • Adenoma / pathology*
  • Adenoma / surgery
  • Adult
  • Aged
  • Biomarkers / analysis
  • Female
  • Follow-Up Studies
  • Growth Hormone-Secreting Pituitary Adenoma / drug therapy
  • Growth Hormone-Secreting Pituitary Adenoma / metabolism
  • Growth Hormone-Secreting Pituitary Adenoma / pathology*
  • Growth Hormone-Secreting Pituitary Adenoma / surgery
  • Hormone Antagonists / pharmacology*
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Preoperative Care*
  • Prognosis
  • Receptors, Somatostatin / metabolism*
  • Retrospective Studies
  • Somatostatin / analogs & derivatives*

Substances

  • Biomarkers
  • Hormone Antagonists
  • Receptors, Somatostatin
  • SSTR2 protein, human
  • Somatostatin