Treatment of Growth Hormone-Deficient Adults with Recombinant Human Growth Hormone Increases the Concentration of Growth Hormone in the Cerebrospinal Fluid and Affects Neurotransmitters

Abstract

In a double-blind, placebo-controlled trial, the effects of recombinant human growth hormone were studied on cerebrospinal fluid concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), monoamine metabolites, neuropeptides and endogenous opioid peptides. Twenty patients, 10 patients in each of 2 groups, with adult-onset, growth hormone deficiency were treated for 1 month with recombinant human growth hormone (0.25 U/kg/week) or placebo. All the patients received the appropriate thyroid, adrenal and gonadal hormone replacement. In cerebrospinal fluid, the mean concentration of growth hormone increased from 13.3 ± 4.4 to 149.3 ± 22.2 µU/1 (p = 0.002), during recombinant human growth hormone treatment. The cerebrospinal fluid IGF-1 concentration increased from 0.67 ± 0.04 to 0.99 ± 0.10 µg/1 (p = 0.005) and the IGFBP-3 concentration rose from 13.4 ± 1.25 to 17.5 ± 1.83 µg/l(p = 0.002). The dopamine metabolite homovanillic acid decreased from 282.1 ± 36.0 to 234.3 ± 26.5 nmol/l (p = 0.02) and the vasoactive intestinal peptide decreased from 4.1 ± 0.6 to 3.7 ± 0.4 pmol/l (p = 0.03). Cerebrospinal fluid immunoreactive β-endorphin increased from 24.4 ± 1.8 to 29.9 ± 2.1 pmol/l (p = 0.002). There were no significant changes compared to baseline in the cerebrospinal fluid concentrations of enkephalins, dynorphin A, the norepinephrine metabolite 3-methoxy-4-hydroxyphenyl-ethyleneglycol, the serotonin metabolite 5-hydroxyindoleacetic acid, γ-aminobutyric acid, somatostatin or corticotropin-releasing factor. We conclude that treatment with recombinat human growth hormone causes a tenfold increase in growth hormone in the cerebrospinal fluid, thereby indicating that recombinant human growth hormone passes the blood-cerebrospinal fluid barrier. The cerebrospinal fluid concentrations of IGF-1 and IGFBP-3 increased significantly. Simultaneously, the cerebrospinal fluid concentrations of homovanillic acid and vasoactive intestinal peptide decreased and the concentration of β-endorphin immunoreactivities increased significantly. These changes might explain the improved quality-of-life in patients with growth hormone deficiency following replacement therapy with growth hormone.