Z A Efstathiadou1, A Bargiota2, A Chrisoulidou3, G Kanakis4, L Papanastasiou5, A Theodoropoulou6, S K Tigas7, D A Vassiliadi8, M Alevizaki9, S Tsagarakis10. 1. Department of Endocrinology, "Hippokration" General Hospital of Thessaloniki, Konstantinoupoleos 49, 54642, Thessaloníki, Greece. zefsta@hotmail.com. 2. Department of Endocrinology, University of Thessaly, Larissa, Greece. 3. Department of Endocrinology-Endocrine Oncology, Theagenion Cancer Hospital, Thessaloniki, Greece. 4. Endocrine Unit, Athens Naval and VA General Hospital, Athens, Greece. 5. Department of Endocrinology and Diabetes Center, Athens General Hospital "G. Gennimatas", Athens, Greece. 6. Division of Endocrinology, Department of Internal Medicine, University Hospital of Patras, Rio, Greece. 7. Department of Endocrinology, University of Ioannina, Ioannina, Greece. 8. Endocrine Unit, Second Department of Internal Medicine, University of Athens, Medical School, "Attikon" Hospital, Athens, Greece. 9. Endocrine Unit, Department of Medical Therapeutics, Athens University School of Medicine, Athens, Greece. 10. Department of Endocrinology, Evangelismos Hospital, Athens, Greece.
Abstract
OBJECTIVE: Somatic mutations in the GNAS1 gene, which encodes the alpha-subunit of G stimulatory proteins (gsp), are frequently detected in somatotroph pituitary tumors and have been associated to specific clinical and histopathological characteristics. However, the question whether the presence of a somatic gsp mutation affects the response to somatostatin analog treatment remains unresolved. DESIGN: Following a literature search, we performed a meta-analysis, including 8 eligible studies, in order to estimate the effect of gsp mutation on the percent reduction of growth hormone (GH) levels during an acute octreotide suppression test (OST). A total of 310 patients with acromegaly [126 gsp (+) and 184 gsp (-)] were included in the analysis. RESULTS: The presence of the gsp mutation was related with a greater reduction in GH levels on OST [Weighted Mean Difference (WMD): 9.08 % (95 % CI, 2.73, 15.42); p = 0.005; random effects model]. There was significant heterogeneity for this effect estimate (I(2) = 58 %, p value for heterogeneity = 0.02). A sensitivity analysis after exclusion of a study with different methodology of OST provided similar estimates [WMD: 6.93 % (95 % CI, 1.40, 12.46); p = 0.01], albeit with no significant heterogeneity (I(2) = 35 %, p value for heterogeneity = 0.16). CONCLUSIONS: The present meta-analysis suggests a role for gsp mutation as a prognostic factor of treatment response to somatostatin analogs.
OBJECTIVE: Somatic mutations in the GNAS1 gene, which encodes the alpha-subunit of G stimulatory proteins (gsp), are frequently detected in somatotroph pituitary tumors and have been associated to specific clinical and histopathological characteristics. However, the question whether the presence of a somatic gsp mutation affects the response to somatostatin analog treatment remains unresolved. DESIGN: Following a literature search, we performed a meta-analysis, including 8 eligible studies, in order to estimate the effect of gsp mutation on the percent reduction of growth hormone (GH) levels during an acute octreotide suppression test (OST). A total of 310 patients with acromegaly [126 gsp (+) and 184 gsp (-)] were included in the analysis. RESULTS: The presence of the gsp mutation was related with a greater reduction in GH levels on OST [Weighted Mean Difference (WMD): 9.08 % (95 % CI, 2.73, 15.42); p = 0.005; random effects model]. There was significant heterogeneity for this effect estimate (I(2) = 58 %, p value for heterogeneity = 0.02). A sensitivity analysis after exclusion of a study with different methodology of OST provided similar estimates [WMD: 6.93 % (95 % CI, 1.40, 12.46); p = 0.01], albeit with no significant heterogeneity (I(2) = 35 %, p value for heterogeneity = 0.16). CONCLUSIONS: The present meta-analysis suggests a role for gsp mutation as a prognostic factor of treatment response to somatostatin analogs.
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