The GH-IGF system in amyotrophic lateral sclerosis: correlations between pituitary GH secretion capacity, insulin-like growth factors and clinical features

Eur J Neurol. 2010 May;17(5):666-71. doi: 10.1111/j.1468-1331.2009.02896.x. Epub 2009 Dec 7.

Abstract

Background and purpose: The growth hormone (GH) and insulin-like growth factor (IGF) system may be involved in neurodegenerative processes, and some abnormalities have been reported in amyotrophic lateral sclerosis (ALS). Our aim was to investigate the GH-IGF axis in patients with ALS and evaluate correlations between this endocrine system and clinical features.

Methods: Serum levels of GH, IGF-I, IGF-II, insulin, IGF-binding protein 1 (IGF-BP1), and IGF-binding protein 3 (IGF-BP3) were measured in 25 patients with ALS and 25 age-, gender-, and BMI-matched healthy controls. A GHRH plus arginine test was performed in patients and controls. Clinical status of patients was evaluated with the ALS Functional Rating Scale - Revised (ALSFRS-R) and upper motor neuron (UMN) score.

Results: GHRH plus arginine test showed GH deficiency (GHD) in 13 (52%) patients with ALS; severe GHD was found in 6 (24%) and partial GHD in 7 (28%) patients. IGF-I levels were significantly higher in patients with ALS than in healthy controls (182.9 +/- 90.8 vs. 139.4 +/- 58.1 ng/ml; P = 0.015). IGF-I levels were higher in patients with ALS with UMN score >10 than those with UMN score <10 (217.8 +/- 100.8 vs. 155.5 +/- 74.6 ng/ml, P = 0.05). IGF-II levels were significantly lower in patients with ALS than in healthy controls (720.9 +/- 215 vs. 1001.9 +/- 475.4 ng/ml; P = 0.03).

Conclusions: The results demonstrate an impairment of the GH-IGFs system in ALS. The degenerative process in ALS might lead to a compensatory increase in IGF-I in an attempt to provide additional support to motor neurons or degenerating muscle fibers. The decrease in IGF-II levels may also be of pathological significance.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / etiology
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology
  • Female
  • Gonadotropin-Releasing Hormone / metabolism
  • Growth Hormone / blood
  • Growth Hormone / metabolism*
  • Humans
  • Hypothalamo-Hypophyseal System / metabolism
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Protein 1 / metabolism
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor II / metabolism
  • Male
  • Middle Aged
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Pituitary Diseases / complications
  • Pituitary Diseases / metabolism*
  • Pituitary Diseases / pathology
  • Pituitary Gland / metabolism*
  • Up-Regulation / physiology

Substances

  • IGFBP1 protein, human
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Gonadotropin-Releasing Hormone
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Growth Hormone