title: In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5.
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.
authors.affiliation: Department of Endocrine and Medical Sciences (DiSEM) & Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV, 6, 16132 Genova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Gatto
authors.forename: Federica
authors.initials: F
authors.lastname: Barbieri
authors.forename: Lara
authors.initials: L
authors.lastname: Castelletti
authors.forename: Marica
authors.initials: M
authors.lastname: Arvigo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pattarozzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Annunziata
authors.forename: Alexandru
authors.initials: A
authors.lastname: Saveanu
authors.forename: Francesco
authors.initials: F
authors.lastname: Minuto
authors.forename: Lucio
authors.initials: L
authors.lastname: Castellan
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zona
authors.forename: Tullio
authors.initials: T
authors.lastname: Florio
authors.forename: Diego
authors.initials: D
authors.lastname: Ferone
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D052684:Thyrotrophs / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5; D013972:Thyrotropin; D015282:Octreotide