title: Biological characteristics of growth hormone-producing pituitary adenomas are different according to responsiveness to thyrotropin-releasing hormone.
abstract: OBJECTIVE
  The paradoxical response of GH to TRH in patients with acromegaly has been previously reported. However, few reports have focused on tumor characteristics reflected by this response. This study aimed to clarify the relationship between TRH-induced GH responsiveness and other tumor characteristics.
  
  
  METHODS
  Patients with acromegaly who underwent initial surgery between 2000 and 2012 were divided into TRH-responder and nonresponder groups. Clinical features were compared between the two groups with respect to tumor size, Knosp grade, endocrinological profiles, and histopathological findings revealed by cytokeratin staining. Tumor size was quantitatively evaluated with volumetry. Cytokeratin staining patterns were categorized into three groups: sparsely granulated type, densely granulated type, and intermediate type.
  
  
  RESULTS
  Sixty-two patients were included in the study. TRH responders (n = 45) showed significantly smaller tumor size than nonresponders (n = 17) (2.78 ± 4.71 vs. 7.56 ± 9.00 ml, P < 0.005). In addition, TRH responders showed significantly higher preoperative basal GH per volume ratio than nonresponders (10.1 ± 8.4 vs. 7.72 ± 11.85 ng/ml(2), P < 0.05). Logarithmic regression modeling showed significant correlation between TRH responsiveness and tumor volume (r = -0.341; P < 0.01). The difference between cytokeratin staining patterns was also significant: sparsely granulated-type adenomas were found in only 13% of TRH responders but in 64% of nonresponders (P < 0.0005). TRH responders showed higher GH suppression rates in the octreotide test compared with nonresponders (86 vs. 68%, P < 0.01).
  
  
  CONCLUSIONS
  The present data suggest that the responsiveness of serum GH level to TRH reflects significant tumor biological characteristics.
authors.affiliation: Departments of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Arita
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Satoru
authors.initials: S
authors.lastname: Oshino
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kitamura
authors.forename: Michio
authors.initials: M
authors.lastname: Otsuki
authors.forename: Soji
authors.initials: S
authors.lastname: Kasayama
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimokawa
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
authors.forename: Youichi
authors.initials: Y
authors.lastname: Saitoh
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism* / Q000473:pathology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
chemical_list: D019382:Human Growth Hormone; D013973:Thyrotropin-Releasing Hormone