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      Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues

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          Abstract

          The expression of somatostatin receptor subtypes (SSTRs) in pituitary growth hormone- (GH-) secreting adenomas may predict the response to somatostatin analogues (SSA). Our aim was to evaluate the value of the immunohistochemical (IHC) scores of 2 subtypes, SSTR2 and SSTR5, in predicting the short-term efficacy of SSA therapy in patients with active acromegaly. Ninety-three newly diagnosed acromegalic patients were included in our study. These patients were categorized into either a SSA-pretreated group (SA, n = 63) or a direct-surgery group (DS, n = 30), depending on whether or not presurgical SSA treatment was received. IHC analysis, using a 12-grade scoring system, with rabbit monoclonal antibodies against SSTR2 and SSTR5, was performed on all adenoma tissues. The reduction of GH, IGF-1, and tumor size after treatment with SSA for 3 months was measured. Compared with that in the DS group, SSTR2 expression was lower in the SA group. Additionally, in the SA group, SSTR2 expression was positively correlated with the reduction of IGF-1 and tumor volume. However, there was no correlation between the SSTR5 score and the efficacy of SSA. In conclusion, the protein expression of SSTR2, but not of SSTR5, is a valuable indicator in predicting biochemical and tumor size response to short-term SSA treatment in acromegalic patients.

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          Acromegaly pathogenesis and treatment.

          Shlomo Melmed (2009)
          Dysregulated growth hormone (GH) hypersecretion is usually caused by a GH-secreting pituitary adenoma and leads to acromegaly - a disorder of disproportionate skeletal, tissue, and organ growth. High GH and IGF1 levels lead to comorbidities including arthritis, facial changes, prognathism, and glucose intolerance. If the condition is untreated, enhanced mortality due to cardiovascular, cerebrovascular, and pulmonary dysfunction is associated with a 30% decrease in life span. This Review discusses acromegaly pathogenesis and management options. The latter include surgery, radiation, and use of novel medications. Somatostatin receptor (SSTR) ligands inhibit GH release, control tumor growth, and attenuate peripheral GH action, while GH receptor antagonists block GH action and effectively lower IGF1 levels. Novel peptides, including SSTR ligands, exhibiting polyreceptor subtype affinities and chimeric dopaminergic-somatostatinergic properties are currently in clinical trials. Effective control of GH and IGF1 hypersecretion and ablation or stabilization of the pituitary tumor mass lead to improved comorbidities and lowering of mortality rates for this hormonal disorder.
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            Resistance to somatostatin analogs in acromegaly.

            R Auriemma, Rosario Pivonello, Annamaria Colao … (2011)
            Somatostatin analogs (SA) are widely used in acromegaly, either as first-line or adjuvant treatment after surgery. First-line treatment with these drugs is generally used in the patients with macroadenomas or in those with clinical conditions so severe as to prevent unsafe reactions during anesthesia. Generally, the response to SA takes into account both control of GH and IGF-I excess, with consequent improvement of clinical symptoms directly related to GH and IGF-I excess, and tumor shrinkage. This latter effect is more prominent in the patients treated first-line and bearing large macroadenomas, but it is also observed in patients with microadenomas, even with little clinical implication. Predictors of response are patients' gender, age, initial GH and IGF-I levels, and tumor mass, as well as adequate expression of somatostatin receptor types 2 and 5, those with the highest affinity for octreotide and lanreotide. Only sporadic cases of somatostatin receptor gene mutation or impaired signaling pathways have been described in GH-secreting tumors so far. The response to SA also depends on treatment duration and dosage of the drug used, so that a definition of resistance based on short-term treatments using low doses of long-acting SA is limited. Current data suggest that response to these drugs is better analyzed taking together biochemical and tumoral effects because only the absence of both responses might be considered as a poor response or resistance. This latter evidence seems to occur in 25% of treated patients after 12 months of currently available long-acting SA.
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              Tumor Shrinkage With Lanreotide Autogel 120 mg as Primary Therapy in Acromegaly: Results of a Prospective Multicenter Clinical Trial

              Philippe J. Caron, John Bevan, Stephan Petersenn … (2013)
              Context: Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation. Objective: The aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas. Design: PRIMARYS was a 48-week, multicenter, open-label, single-arm study. Setting: The study was conducted at specialist endocrine centers. Patients: Treatment-naïve acromegalic patients with GH-secreting macroadenomas participated in the study. Intervention: Lanreotide Autogel 120 mg was administered sc every 28 days (without dose titration). Outcome Measures: The primary endpoint was the proportion of patients with clinically significant (≥20%) tumor volume reduction (TVR) at week 48/last post-baseline value available using central assessments from three readers. The null hypothesis (H 0) for the primary endpoint was that the proportion with TVR was ≤55%. Secondary endpoints included: TVR at other time points, GH and IGF-1, acromegalic symptoms, quality of life (QoL), and safety. Results: Sixty-four of 90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/last post-baseline value available was achieved by 62.9% (95% confidence interval, 52.0, 72.9) of 89 patients in the primary analysis (intention-to-treat population; H 0 not rejected) and 71.9–75.3% in sensitivity (n = 89) and secondary analyses (n = 63) (H 0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance. Conclusions: Primary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor volume, GH and IGF-1, and acromegalic symptoms, and improves QoL.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Endocrinol
                Journal ID (iso-abbrev): Int J Endocrinol
                Journal ID (publisher-id): IJE
                Title: International Journal of Endocrinology
                Publisher: Hindawi
                ISSN (Print): 1687-8337
                ISSN (Electronic): 1687-8345
                Publication date (Print): 2017
                Publication date (Electronic): 15 March 2017
                Volume: 2017
                Electronic Location Identifier: 9606985
                Affiliations
                1Division of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai 200040, China
                2Institute of Endocrinology and Diabetology, Fudan University, Shanghai 200040, China
                3Department of Endocrinology, Kunshan Rehabilitation Hospital, Suzhou, Jiangsu 215314, China
                4Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China
                5Shanghai Pituitary Tumor Center, Shanghai 200040, China
                6Department of Pathology, Huashan Hospital, Fudan University, Shanghai 200040, China
                7Department of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215004, China
                Author notes

                Academic Editor: Andrea G. Lania

                Author information
                http://orcid.org/0000-0001-5366-1353
                Article
                DOI: 10.1155/2017/9606985
                PMC ID: 5370518
                SO-VID: 171ca36d-ecbb-4193-9e32-aabbba3d9190
                Copyright © Copyright © 2017 Wenjuan Liu et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 28 November 2016
                Date accepted : 23 January 2017
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81370938
                Award ID: 81471041
                Funded by: Shanghai Municipal Commission of Health and Family Planning
                Award ID: XYQ2011002
                Funded by: Shanghai Science and Technology Commission
                Award ID: 11PJ1402000
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

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