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

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.

Automated 22-kD Growth Hormone–Specific Assay without Interference from Pegvisomant

“…This finding highlights the large differences in isoform specificity among currently available assays. One could argue that, in theory, by measuring only 22-kD GH, information about other isoforms contributing to total bioactive GH might be missed (5,28,29 ). However, 22-kD GH is the most abundant, bioactive form of GH, and no evidence exists to suggest isolated changes in other isoforms during specific clinical situations.…”

Growth hormone assays: current methodologies and their limitations

“…It is a matter of debate whether a more specific or a more permissive recognition of GH isoforms is preferable from a clinical point of view. It has been shown convincingly that different isoforms are biologically active [34], and therefore one is potentially missing information with assays measuring only one isoform [14].…”

Pituitary development and physiology

“…Alternative splicing with omission of amino acids 32-46 results in a 20-kDa protein, which circulates in lower quantities. In humans, the somatic growth and diabetogenic effects of the 20 kDa and 22 kDa forms are similar [92].…”