Effect of growth hormone replacement therapy on plasma diacron-reactive oxygen metabolites and endothelial function in Japanese patients: The GREAT clinical study

• Published in: ENDOCRINE JOURNAL Vol. 65; no. 1; pp. 101 - 111
• Main Authors: Suzuki, Kunihiro, Yanagi, Kazunori, Shimizu, Masanori, Wakamatsu, Sho, Niitani, Takafumi, Hosonuma, Soichiro, Sagara, Masaaki, Aso, Yoshimasa
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Japan Endocrine Society 01.01.2018; Japan Science and Technology Agency
• Subjects: Arteriosclerosis; Atherogenesis; Blood pressure; Diacron-reactive oxygen metabolites levels; Growth hormone; Growth hormone deficiency; Growth hormone replacement; Growth hormones; Hormone replacement therapy; Hyperemia; Insulin; Insulin-like growth factor I; Insulin-like growth factors; Metabolites; Oxidative stress; Patients; Peripheral arterial tonometry; Pituitary; Growth hormone replacement; Diacron-reactive oxygen metabolites levels; Peripheral arterial tonometry; Growth hormone deficiency
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.EJ17-0330

Patients with growth hormone deficiency (GHD) have an increased risk of atherosclerosis and vascular mortality. Evidence suggests that endothelial dysfunction is involved in all stages of atherogenesis. This study examined the effect of growth hormone (GH) replacement therapy on diacron-reactive oxygen metabolites (d-ROMs) and endothelial function in Japanese patients with GHD, using peripheral arterial tonometry. This was an open-label, prospective, case-control study. Nine patients with GHD who had not previously received any GH replacement therapy were enrolled. The following parameters were evaluated at baseline (before treatment), and after 24 weeks of GH replacement therapy: endothelial function using the reactive hyperemia index (RHI; EndoPAT® system), d-ROMs, blood pressure, and fasting lipid levels. Plasma GH and insulin-like growth factor-1 (IGF-1) levels were measured at baseline and after 24 weeks of GH replacement therapy. We also enrolled eight controls with pituitary disease but no GH deficiency. Over 24 weeks of GH replacement therapy, the serum IGF-1 levels normalized with significant improvement in the RHI (from 1.65 ± 0.33 to 1.92 ± 0.26, p < 0.05) and decreased d-ROM levels (from 356.8 ± 64.1 to 303.1 ± 43.3 U.CARR, p < 0.05). There were no significant improvements in the RHI or d-ROM levels in controls. GH replacement therapy in Japanese patients with GHD may be mediated by the reduced oxidative stress and the d-ROMs associated with the treatment.