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

J Clin Endocrinol Metab. 2004 Apr;89(4):1562-71. doi: 10.1210/jc.2003-030716.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Abdomen
  • Adipose Tissue / pathology
  • Adult
  • Body Composition
  • Bone and Bones / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Glucose / metabolism
  • Human Growth Hormone / administration & dosage*
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / chemistry
  • Human Growth Hormone / deficiency*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / metabolism
  • Lipids / blood
  • Male
  • Metabolism, Inborn Errors / drug therapy
  • Middle Aged
  • Molecular Weight
  • Quality of Life
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / chemistry
  • Treatment Outcome

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • Lipids
  • Recombinant Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Glucose