In vitro head-to-head comparison between octreotide and pasireotide in gh-secreting pituitary adenomas

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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

53 Citaten (Scopus)

Samenvatting

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 (236.8%) and PAS (237.1%) 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.

Originele taal-2Engels
Pagina's (van-tot)2009-2018
Aantal pagina's10
TijdschriftJournal of Clinical Endocrinology and Metabolism
Volume102
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - 1 jun. 2017
Extern gepubliceerdJa

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