Dissecting the In Vitro Efficacy of Octreotide and Cabergoline in GH- and GH/PRL-Secreting Pituitary Tumors

Federico Gatto*, Richard A Feelders, Peter M van Koetsveld, Fadime Dogan, Sebastian J C C M M Neggers, Aart-Jan van der Lelij, Jessica Amarù, Diego Ferone, Leo J Hofland

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Context Cabergoline (CAB) is an off-label medical therapy for acromegaly, overshadowed by first-generation somatostatin receptor ligands, eg, octreotide (OCT). Objective This was a head-to-head comparison between OCT and CAB in inhibiting growth hormone (GH) secretion in primary cultures of GH- and GH/prolactin (PRL)-secreting tumors; we also investigated the role of somatostatin (SST) and dopamine type 2 (D2R) receptor expression. Methods We evaluated the antisecretory effect of OCT and CAB, together with receptor mRNA expression, in 23 tumor cultures obtained from acromegaly patients referred to the Erasmus Medical Center (Rotterdam, The Netherlands). GH concentrations in cell culture media were determined after 72-hour OCT and CAB treatment (10 nM). Results OCT showed a slightly higher efficacy compared with CAB (GH decrease -39.5% vs -32.5%, P = 0.079). The effect of the 2 drugs was superimposable in GH/PRL co-secreting tumors (-42.1% vs -44.8%), where SST1 and D2R had a higher expression compared with the pure GH-secreting tumors (P = 0.020 and P = 0.026). OCT was more effective than CAB in 8/23 cultures, while CAB was more effective than OCT in 3/23 (CAB+ group). In CAB+ tumors, SST1 expression was higher compared with the other groups (P = 0.034). At receiver operating characteristic (ROC) curve analysis, SST1 and D2R discriminated between GH and GH/PRL co-secretion (AUC 0.856, P = 0.013; AUC 0.822, P = 0.024). SST1 was the best predictor of CAB response (>= 50% GH reduction, AUC 0.913, P = 0.006; 80% sensitivity, 94% specificity). Conclusion OCT is 5% to 10% more effective than CAB in vitro. SST1 mRNA expression can represent a reliable marker of GH/PRL co-secreting tumors showing a preferential response to CAB treatment.
Original languageEnglish
Article numberdgac675
Pages (from-to)E98-E109
JournalThe Journal of clinical endocrinology and metabolism
Volume108
Issue number5
Early online date22 Nov 2022
DOIs
Publication statusPublished - 1 May 2023

Bibliographical note

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© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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