Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 102, Issue 6, Pages 2009-2018Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2017-00135
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Funding
- Novartis Italy
- Ipsen
- Novartis
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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 sst(2)/sst(5) 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 sst(2) mRNA expression and lower sst(2)/sst(5) 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.
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