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

CONTEXT: Cabergoline (CAB) is an off-label medical therapy for acromegaly, overshadowed by first-generation somatostatin receptor ligands, e.g. octreotide (OCT). OBJECTIVE: Head-to-head comparison between OCT and CAB in inhibiting growth hormone (GH) secretion in primary cultures of GH- and GH/PRL-secreting tumors. To investigate the role of somatostatin (SST) and dopamine type 2 (D2R) receptor expression. DESIGN: To evaluate the antisecretory effect of OCT and CAB, together with receptor mRNA expression, in 23 tumor cultures. SETTING AND PATIENTS: Acromegaly patients referred to the Erasmus Medical Center (Rotterdam, The Netherlands). INTERVENTIONS: 72-hour OCT and CAB treatment (10 nM). MAIN OUTCOME MEASURES: GH concentrations in cell culture media. RESULTS: OCT showed a slightly higher efficacy compared with CAB (GH decrease -39.5% vs. -32.5%, p = 0.079). The effect of the two drugs was superimposable in GH/PRL co-secreting tumors (-42.1% vs. -44.8%), where SST1 and D2R had a higher expression compared to the pure GH-secreting ones (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 to the other groups (p = 0.034). At 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). CONCLUSIONS: OCT is 5-10% 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