In Vitro Head-to-Head Comparison Between Octreotide and Pasireotide in GH-Secreting Pituitary Adenomas

J Clin Endocrinol Metab. 2017 Jun 1;102(6):2009-2018. doi: 10.1210/jc.2017-00135.

Abstract

Context: First-generation somatostatin analogs (SSAs), such as octreotide (OCT), are the first line medical therapy for acromegaly. Pasireotide (PAS), a newly developed SSA, has shown promising results in the treatment of acromegaly.

Objective: To compare the antisecretory effect of OCT and PAS in primary cultures of growth hormone (GH)-secreting pituitary adenomas (GH-omas). To correlate responses with the adenoma somatostatin receptor (SSTR) profile.

Design: The effect of OCT and PAS on GH (and PRL) secretion was tested in 33 GH-oma cultures. SSTR expression was evaluated in adenoma samples.

Setting and patients: Patients with acromegaly referred to the Erasmus Medical Center (Rotterdam, The Netherlands).

Interventions: OCT and PAS treatment for 72 hours (10 nM).

Main outcome measures: GH (and PRL) concentrations in cell culture media. SSTR expression in adenoma samples.

Results: The overall effect of OCT (-36.8%) and PAS (-37.1%) on GH secretion was superimposable. We identified three adenoma groups: PAS+ (PAS more effective than OCT), n = 6; PAS = OCT, n = 22; and OCT+ (OCT more effective than PAS), n = 5. PAS+ adenomas showed lower somatostatin receptor subtype (sst)2 messenger RNA (mRNA) and sst2/sst5 mRNA ratio, compared with the other groups (P < 0.05). PAS inhibited PRL hypersecretion more than OCT (P < 0.01).

Conclusions: Overall, OCT and PAS equally reduced GH secretion in vitro. Adenomas with lower sst2 mRNA expression and lower sst2/sst5 mRNA ratio were better responders to PAS compared with OCT. SSTR evaluation in GH-omas may become a tool for tailored SSA treatment in acromegaly.

Publication types

  • Comparative Study

MeSH terms

  • Adenoma / genetics
  • Adenoma / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Female
  • Growth Hormone-Secreting Pituitary Adenoma / genetics
  • Growth Hormone-Secreting Pituitary Adenoma / metabolism*
  • Human Growth Hormone / drug effects*
  • Human Growth Hormone / metabolism
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Octreotide / pharmacology*
  • Polymerase Chain Reaction
  • Prolactin / drug effects*
  • Prolactin / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacology
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Antineoplastic Agents, Hormonal
  • RNA, Messenger
  • Receptors, Somatostatin
  • somatostatin receptor 3
  • Human Growth Hormone
  • Somatostatin
  • somatostatin receptor 5
  • Prolactin
  • pasireotide
  • somatostatin receptor 2
  • Octreotide