Effect of chronic metabolic acidosis on the growth hormone/IGF-1 endocrine axis: new cause of growth hormone insensitivity in humans

Kidney Int. 1997 Jan;51(1):216-21. doi: 10.1038/ki.1997.26.


The effects of metabolic acidosis on growth hormone and IGF-1 are poorly understood. We investigated the effects of chronic metabolic acidosis (induced by administration on NH4Cl, 4.2 mmol/kg body wt/day) on the growth hormone/IGF-1 endocrine axis in 6 normal male volunteers during metabolic balance conditions. NH4Cl administration resulted in hyperchloremic metabolic acidosis with plasma bicarbonate decreasing from 25 +/- 0.4 to 15.5 +/- 0.9 mmol/liter (P < 0.001). Metabolic acidosis significantly decreased serum IGF-1 concentration from 45 +/- 6 to 33 +/- 6 nmol/liter (P = 0.002), while serum IGF binding protein 3 concentration was not affected significantly. The growth hormone response to growth hormone releasing factor administration (1 microgram per kg body wt, intravenous bolus) was enhanced significantly during acidosis. The IGF-1 response to growth hormone administration (0.1 U kg body wt subcutaneously, every 12 hr for 48 hr) was blunted significantly during acidosis. Apparent endogenous serum half-life and metabolic clearance rates of growth hormone were not altered significantly by acidosis. Metabolic acidosis in humans results in a significant decrease in serum IGF-1 concentration without a demonstrable effect on IGF binding protein 3, and is related to a resistance to the hepatocellular action of growth hormone. The primary defect in the growth hormone/IGF-1 axis occurs via an impaired IGF-1 response to circulating growth hormone with consequent diminution of normal negative feedback inhibition of IGF-1 on growth hormone, as evidenced by the exaggerated growth hormone response to growth hormone releasing factor administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis / chemically induced
  • Acidosis / metabolism*
  • Ammonium Chloride
  • Chronic Disease
  • Endocrine Glands / metabolism
  • Evaluation Studies as Topic
  • Growth Disorders / metabolism*
  • Growth Disorders / physiopathology
  • Growth Hormone-Releasing Hormone / pharmacology
  • Human Growth Hormone / drug effects
  • Human Growth Hormone / metabolism*
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Male


  • Ammonium Chloride
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Growth Hormone-Releasing Hormone