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In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5

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Abstract

Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of pituitary adenomas. Medical therapy with somatostatin analogues (SSAs) effectively reduces TSH secretion in approximately 80% of patients and induces shrinkage in about 45% of tumors. According with previous data, resistance to SSA treatment might be due to heterogeneity in somatostatin receptors (SSTRs) expression. We report the case of TSHoma in a 41-year-old man treated with octreotide LAR that caused a dramatic decrease of TSH and thyroid hormones and tumor shrinkage already after 3 months of pre-surgical therapy. In search of potential molecular determinants of octreotide effectiveness, we measured, in primary cultures from this tumor, SSTR and dopamine D2 receptor (D2R) expression, and octreotide and/or cabergoline effects on TSH secretion and cell proliferation. SSTR5 and D2R expression was higher than SSTR2. Octreotide significantly inhibited TSH secretion more effectively than cabergoline (P < 0.001), whereas the combined treatment was comparable with cabergoline alone. Similarly, octreotide resulted more effective than cabergoline on cell proliferation, while the combination did not show any additive or synergistic effects. In conclusion, the significant antisecretive and antiproliferative effect of octreotide in this patient might be related to the high expression of SSTR5, in the presence of SSTR2. After reviewing the literature, indeed, in line with previous observations, we hypothesize that SSTR5/SSTR2 ratio in TSHomas may represent a useful marker in predicting the outcome of therapy with SSAs. The role of D2R should be further explored considering that the presence of D2R can influence SSTRs functionality.

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Acknowledgments

We sincerely acknowledge Anne-Laure Germanetti for performing the quantitative RT-PCR analysis. This study was partially supported by grant from Italian Minister of Instruction, University and Research (PRIN 2008 n. 2008LFK7J5_004).

Conflict of interest

The Authors report no conflict of interest in the present manuscript.

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Authors and Affiliations

  1. Department of Endocrine and Medical Sciences (DiSEM) & Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV, 6, 16132, Genova, Italy

    Federico Gatto, Marica Arvigo, Francesca Annunziata, Francesco Minuto & Diego Ferone

  2. Laboratory of Pharmacology, Department of Oncology, Biology and Genetics, University of Genova, Genova, Italy

    Federica Barbieri, Alessandra Pattarozzi & Tullio Florio

  3. Neuroradiology Unit, San Martino University Hospital, Genova, Italy

    Lara Castelletti & Lucio Castellan

  4. Interactions Cellulaires Neuroendocriniennes, Unité Mixte de Recherche, Centre National de la Recherche Scientifique, Institut Fédératif Jean Roche, Faculté de Médecine Nord, Marseille Cedex, France

    Alexandru Saveanu

  5. Department of Neurosurgery, San Martino University Hospital, Genova, Italy

    Gianluigi Zona

Authors
  1. Federico Gatto
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  2. Federica Barbieri
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  3. Lara Castelletti
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  4. Marica Arvigo
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  5. Alessandra Pattarozzi
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  6. Francesca Annunziata
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  7. Alexandru Saveanu
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  8. Francesco Minuto
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  9. Lucio Castellan
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  10. Gianluigi Zona
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  11. Tullio Florio
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  12. Diego Ferone
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Corresponding author

Correspondence to Diego Ferone.

Additional information

Federico Gatto and Federica Barbieri equally contributed to the paper.

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Gatto, F., Barbieri, F., Castelletti, L. et al. In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5. Pituitary 14, 141–147 (2011). https://doi.org/10.1007/s11102-010-0271-2

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  • DOI: https://doi.org/10.1007/s11102-010-0271-2

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