title: Somatostatin Receptor Expression in GH-Secreting Pituitary Adenomas Treated with Long-Acting Somatostatin Analogues in Combination with Pegvisomant.
abstract: BACKGROUND
  Growth hormone-secreting pituitary adenomas (somatotroph adenoma) predominantly express somatostatin receptors (SSTRs) subtypes 2 and 5. Higher SSTR2 expression on somatotroph adenomas results in a better response to somatostatin analogues (SSAs), which preferentially bind, but also downregulate, SSTR2. The effect of the combined treatment with SSAs and the GH receptor antagonist pegvisomant (PEGV) on SSTR expression in somatotroph adenomas is currently unknown.
  
  
  OBJECTIVE
  To assess SSTR2 and SSTR5 expression in three groups of somatotroph adenomas: drug-naive, treated with long-acting (LA) SSA monotherapy, or LA-SSA/PEGV combination therapy before surgery. Additionally, we evaluated the required PEGV dose to achieve insulin-like growth factor I (IGF-I) normalization in relation to the SSTR expression.
  
  
  METHODS
  At our Pituitary Center Rotterdam, we selected acromegalic patients who underwent transsphenoidal neurosurgery. All patients were eventually treated with LA-SSA/PEGV combination therapy during their medical history. SSTR2 and SSTR5 expression in somatotroph adenoma tissues was determined using immunohistochemistry.
  
  
  RESULTS
  Out of 39 somatotroph adenoma tissue samples, 23 were drug-naive, 9 received pretreatment with LA-SSA and 7 LA-SSA/PEGV combined treatment. SSTR2 expression was significantly higher in treatment-naive compared to combined treatment somatotroph adenomas (p = 0.048), while SSTR5 expression did not differ. Noteworthy, SSTR2 expression in naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization during postsurgical medical treatment (ρ = -0.538, p = 0.024).
  
  
  CONCLUSIONS
  In our specific cohort, the SSTR2 expression was lower in patients pretreated with LA-SSA/PEGV compared to the drug-naive acromegalic patients. Additionally, the SSTR2 expression in treatment-naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization.
authors.affiliation: Endocrinology Section, Department of Internal Medicine, Pituitary Center Rotterdam, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Sanne E
authors.initials: SE
authors.lastname: Franck
authors.forename: Federico
authors.initials: F
authors.lastname: Gatto
authors.forename: Aart Jan
authors.initials: AJ
authors.lastname: van der Lely
authors.forename: Joseph A M J L
authors.initials: JAMJL
authors.lastname: Janssen
authors.forename: Alof H G
authors.initials: AHG
authors.lastname: Dallenga
authors.forename: A Paul
authors.initials: AP
authors.lastname: Nagtegaal
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: Sebastian J C M M
authors.initials: SJCMM
authors.lastname: Neggers
mesh_terms: D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D019382:Human Growth Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009493:Neurosurgery / Q000379:methods; D009666:Nose / Q000601:surgery; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D018709:Statistics, Nonparametric
chemical_list: D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C094573:somatostatin receptor 5; C406545:pegvisomant
keywords: Acromegaly; Growth hormone; Growth hormone receptor antagonist; Insulin-like growth factor I; Pegvisomant; Pituitary adenoma; Somatostatin analogues; Somatostatin receptor