• J. Clin. Endocrinol. Metab. · Nov 2013

    Randomized Controlled Trial

    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.

    • Olivera Casar-Borota, Ansgar Heck, Stefan Schulz, Jahn Marthin Nesland, Jon Ramm-Pettersen, Tove Lekva, Irina Alafuzoff, and Jens Bollerslev.
    • Section of Specialized Endocrinology, Oslo University Hospital, Rikshospitalet, PO Box 4950 Nydalen, 0424 Oslo, Norway. ansgar.heck@medisin.uio.no.
    • J. Clin. Endocrinol. Metab. 2013 Nov 1; 98 (11): E1730-9.

    ContextReduced 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.ObjectiveWe 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.Design, Setting, PatientsThe 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.InterventionTwenty-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).Main Outcome MeasureSSTR 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.ResultsThe 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.ConclusionRabbit 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.

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