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Metabolic Effects of 20-Kilodalton Human Growth Hormone (20K-hGH) for Adults with Growth Hormone Deficiency: Results of an Exploratory Uncontrolled Multicenter Clinical Trial of 20K-hGH

Research and Development Operations (M.H., Y.S.), Nihon Schering K.K., Osaka 532-0004; Department of Medicine 2 (T.T., K.T.), Tokyo Women’s Medical University, Tokyo 162-0054; Department of Medicine 2 (Y.K.), Shimane Medical School, Izumo 693-8501; Department of Internal Medicine 3 (K.C.), Kobe University Graduate School of Medicine, Kobe 650-0017; Clinical Research Institute (A.S.), Center for Endocrine and Metabolic Diseases, Kyoto National Hospital, Kyoto 612-8555; and Toho Medical School (M.I.), Toho University, Tokyo 143-8541, Japan

Address all correspondence and reprint requests to: Mr. Masakane Hayakawa, Project Management Department, R&D Operations, Nihon Schering K.K., 6-64, Nishimiyahara 2-chome, Yodogawa-ku, Osaka 532-0004, Japan. E-mail: mahayakawa{at}schering.co.jp.

The biological effects of 20-kDa human GH (20K-hGH), which is produced in the pituitary by alternative splicing of GH mRNA and comprises approximately 6% of all GH in serum, have not been reported.

We have investigated the metabolic effects of recombinant 20K-hGH in adult patients with GH deficiency in an exploratory study. Three doses of 20K-hGH (0.006, 0.012, and 0.024 mg/kg·d), were administered for 16 wk to three groups (consisting of 18 or 19 subjects), respectively. The 20K-hGH dose-dependently increased serum IGF-I and IGFBP-3 levels, and the lowest dose (0.006 mg/kg) was enough to normalize both hormones by wk 4. Serum osteocalcin levels and urinary deoxypyridinoline excretion were also dose-dependently increased. There was a significant decrease in body fat mass with an increase of lean body mass at the lowest dose of 0.006 mg/kg·d. Blood glucose and serum insulin were increased significantly at 4 wk only in the high-dose group (0.024 mg/kg). Glucose tolerance was slightly impaired in 26–39% of patients in all treatment groups as judged by oral glucose tolerance tests, but there was no development of overt diabetes. The major adverse event in the 20K-hGH treatment was peripheral edema, similar to the incidence reported for 22K-hGH.

The data demonstrated that 20K-hGH had metabolic effects comparable to those of 22K-hGH in humans. The results suggest that 20K-hGH could be used to treat GH-deficient patients, although further studies may be required to investigate the optimum dose and superiority of 20K-hGH over 22K-hGH in a comparative study.

Abbreviations: ALT, Alanine aminotransferase; ANP, atrial natriuretic peptide; AST, aspartate aminotransferase; BFM, body fat mass; BP, binding protein; Cho, cholesterol; CT, computed tomography; CV, coefficient(s) of variation; DL, detection limit(s); EF, ejection fraction; %FS, fractional shortening; GHD, GH deficiency or GH deficient; HbA1c, glycosylated hemoglobin; HDL, high-density lipoprotein; hGH, human GH; hGHR, human GH receptor(s); IGT, impaired glucose tolerance; IRMA, immunoradiometric assay(s); 20K-hGH, 20-kDa hGH; LBM, lean body mass; LDL, low-density lipoprotein; NEFA, nonesterified fatty acid; OGTT, oral glucose tolerance test; QOL, quality of life; V/S, visceral fat to sc fat ratio.

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