title: Effect of chronic metabolic acidosis on the growth hormone/IGF-1 endocrine axis: new cause of growth hormone insensitivity in humans.
abstract: 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.
authors.affiliation: Klinik B für Innere Medizin, Kantonsspital, St. Gallen, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Brüngger
authors.forename: H N
authors.initials: HN
authors.lastname: Hulter
authors.forename: R
authors.initials: R
authors.lastname: Krapf
mesh_terms: D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism*; D000643:Ammonium Chloride; D002908:Chronic Disease; D004702:Endocrine Glands / Q000378:metabolism; D005069:Evaluation Studies as Topic; D006130:Growth Disorders / Q000378:metabolism* / Q000503:physiopathology; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male
chemical_list: D000643:Ammonium Chloride; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone