Michio Otsuki    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor and Division head
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Biological characteristics of growth hormone-producing pituitary adenomas are different according to responsiveness to thyrotropin-releasing hormone
Journal	Formal name：The Journal of clinical endocrinology and metabolism Abbreviation：J Clin Endocrinol Metab ISSN code：19457197 (Electronic)0021972X (Linking)
Domestic / Foregin	Foregin
Volume, Issue, Page	97(8),pp.2741-2747
Author and coauthor	Arita, H. Kinoshita, M. Oshino, S. Kitamura, T. Otsuki, M. Kasayama, S. Shimokawa, T. Shimomura, I. Yoshimine, T. Saitoh, Y.
Publication date	2012
Summary	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). CONCLUSION: The present data suggest that the responsiveness of serum GH level to TRH reflects significant tumor biological characteristics.
DOI	10.1210/jc.2012-1125
Document No.	22569237