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

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.

• Authors: Federico Gatto, Richard A Feelders, Sanne E Franck, Peter M van Koetsveld, Fadime Dogan, Johan M Kros, Sebastian J C M M Neggers, Aart-Jan van der Lely, Steven W J Lamberts, Diego Ferone, Leo J Hofland
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 102 Issue 6 Pg. 2009-2018 (06 01 2017) ISSN: 1945-7197 [Electronic] United States
• PMID: 28323931 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2017 Endocrine Society

Chemical References

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

Topics

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