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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.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2013 Nov; Vol. 98 (11), pp. E1730-9. Date of Electronic Publication: 2013 Oct 03. - Publication Year :
- 2013
-
Abstract
- Context: Reduced expression of somatostatin receptors (SSTRs) in somatotroph adenomas and their potential down-regulation after medical treatment may explain the unsatisfactory response to octreotide in particular acromegalic patients. The expression of SSTRs other than SSTR2a has not been studied in large, unselected cohorts using novel rabbit monoclonal antibodies.<br />Objective: We aimed to determine the expression of SSTRs 1, 2a, 3, and 5 in somatotroph adenomas, to correlate expression with clinical characteristics and the response to octreotide, and to ascertain whether preoperative octreotide treatment affected SSTR expression.<br />Design, Setting, Patients: The study included 78 adenomas from patients operated on consecutively during 2000 to 2010. After exclusion of 13 patients, immunohistochemical analysis with rabbit monoclonal antibodies against SSTRs 1, 2a, 3, and 5 (clones UMB-7, -1, -5, and -4) was performed on 65 adenomas.<br />Intervention: Twenty-eight patients received preoperative octreotide, and 37 patients were operated on without pretreatment. Twenty-six patients were randomized to direct surgery (n = 13) or to octreotide pretreatment (n = 13).<br />Main Outcome Measure: SSTR expression was evaluated using a 12-grade scoring system. The responses to the octreotide test dose (GH reduction) and to 6 months of octreotide (IGF-I reduction) were measured.<br />Results: The majority of adenomas showed membranous expression of SSTRs 2a and 5. SSTR2a expression was reduced in the pretreated group and correlated with the acute octreotide test results and the effect of octreotide treatment. In a linear regression model with SSTR2a expression as the determinant, the correlation with the acute test response improved after adjustment for medical pretreatment.<br />Conclusion: Rabbit monoclonal antibodies are reliable markers of SSTRs in somatotroph adenomas. SSTR2a expression correlated with the response to octreotide and was reduced after octreotide treatment, indicating the need for adjustment when SSTR2a expression is correlated with baseline characteristics. Evaluation of SSTR subtypes may be an important aspect of improving the medical treatment for acromegaly.
- Subjects :
- Adult
Animals
Antibodies, Monoclonal pharmacology
Antineoplastic Agents, Hormonal therapeutic use
Combined Modality Therapy
Female
Humans
Male
Middle Aged
Preoperative Care methods
Rabbits
Receptors, Somatostatin immunology
Time
Treatment Outcome
Acromegaly drug therapy
Acromegaly metabolism
Acromegaly surgery
Adenoma drug therapy
Adenoma metabolism
Adenoma surgery
Growth Hormone-Secreting Pituitary Adenoma drug therapy
Growth Hormone-Secreting Pituitary Adenoma metabolism
Growth Hormone-Secreting Pituitary Adenoma surgery
Octreotide therapeutic use
Receptors, Somatostatin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 98
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 24092823
- Full Text :
- https://doi.org/10.1210/jc.2013-2145