Balance between somatostatin and D2 receptor expression drives TSH-secreting adenoma response to somatostatin analogues and dopastatins

Federico Gatto, F Barbieri, M Gatti, R Wurth, S Schulz, JL Ravetti, G Zona, MD Culler, A Saveanu, M Giusti, F Minuto, Leo Hofland, D Ferone, T Florio

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Abstract

Context First-line therapy for thyrotropin-secreting pituitary adenomas (TSHomas) is neurosurgery, while medical treatment rests mainly on somatostatin analogues. Clinically available sst2-preferring analogues, octreotide and lanreotide, induce normalization of hormone levels in approximately 90% of patients and tumour shrinkage in 45%. Objective We evaluated somatostatin 1, 2, 3 and 5 and dopamine D2 receptor expression in tumour samples from three TSHomas, and the relationships between receptor expression, in vitro antiproliferative response and clinical data, including octreotide test and three months of therapy with octreotide long-acting repeatable (LAR). TSHoma cell proliferation was tested in vitro using octreotide, cabergoline and two chimeric compounds, BIM-23A760 and BIM-23A387. Results All patients showed significant TSH lowering to acute octreotide test, but a hormonal response to long-term treatment was observed in only two patients, showing a high sst5/sst2 ratio. Patient 2, characterized by high expression of sst2 and sst1 and a relative lower expression of sst5, experienced tachyphylaxis after prolonged octreotide treatment. In vitro, the somatostatin/dopamine receptor agonist BIM-23A760 caused the highest antiproliferative effect among those tested. Combined trea Conclusions A high sst5/sst2 ratio might be predictive of a positive outcome to long-term treatment with somatostatin analogues in TSHomas. Moreover, combined somatostatin and D2 receptor targeting might be considered as a potential tool to improve the response rate in octreotide-resistant tumours.
Original languageUndefined/Unknown
Pages (from-to)407-414
Number of pages8
JournalClinical Endocrinology
Volume76
Issue number3
DOIs
Publication statusPublished - 2012

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