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

Autor: Steven W. J. Lamberts, Sanne E Franck, Diego Ferone, Sebastian J C M M Neggers, Leo J. Hofland, Richard A Feelders, Fadime Dogan, Aart Jan van der Lely, Peter M. van Koetsveld, Federico Gatto, Johan M. Kros
Přispěvatelé: Internal Medicine, Pathology
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
genetic structures
Endocrinology
Diabetes and Metabolism

Clinical Biochemistry
Octreotide
Polymerase Chain Reaction
Biochemistry
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Tumor Cells
Cultured

Receptors
Somatostatin

Human Growth Hormone
Somatostatin receptor
Middle Aged
Immunohistochemistry
Growth hormone secretion
Somatostatin
Female
medicine.drug
Adenoma
Adult
medicine.medical_specialty
Adolescent
Antineoplastic Agents
Hormonal

030209 endocrinology & metabolism
Context (language use)
In Vitro Techniques
Young Adult
03 medical and health sciences
Internal medicine
Acromegaly
medicine
Humans
RNA
Messenger

Aged
business.industry
Biochemistry (medical)
medicine.disease
eye diseases
Pasireotide
Prolactin
030104 developmental biology
chemistry
sense organs
Growth Hormone-Secreting Pituitary Adenoma
business
Zdroj: Journal of Clinical Endocrinology and Metabolism, 102(6), 2009-2018. Endocrine Society
ISSN: 1945-7197
0021-972X
Popis: 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.
Databáze: OpenAIRE