Bile acid metabolism in human hyperthyroidism.
Decreased levels of serum cholesterol are a well-recognized finding in hyperthyroidism. Since the conversion to bile acids is an important pathway for the elimination of cholesterol, we studied primary bile acid kinetics in seven hyperthyroid patients before and after medical treatment. Pool sizes, fractional turnover and synthesis rates of cholic acid and chenodeoxycholic acid were determined after oral administration of 50 mg [13C]cholic acid and 50 mg [13C]chenodeoxycholic acid. 13C/12C isotope ratios in serum were measured by capillary gas chromatography/electron impact mass spectrometry. Compared with the euthyroid state, serum cholesterol levels were distinctly lower in hyperthyroidism (150 +/- 33 vs. 261 +/- 51 mg per dl, p less than 0.01). Thyroid hormone excess caused a 34% reduction in cholic acid synthesis (5.8 +/- 2.8 vs. 7.9 +/- 4.2 mu moles per kg per day, p less than 0.02), which was associated with a 47% decrease in cholic acid pool size (11.7 +/- 3.4 vs. 22.0 +/- 5.2 mu moles per kg, p less than 0.01). Chenodeoxycholic acid kinetics exhibited no apparent changes. Thus, total primary bile acid synthesis was diminished by 20% in hyperthyroidism. After normalization of thyroid function, the ratio of cholic acid/chenodeoxycholic acid pool size increased in all patients. This was paralleled by a rise in the ratio of concentrations of cholic acid/chenodeoxycholic acid in serum. The depression of cholic acid synthesis in the presence of unaltered subjects is compatible with an inhibition of hepatic 12 alpha-hydroxylation by thyroid hormone. Furthermore, evidence is provided that, in man, the low serum cholesterol levels found during hyperthyroidism are not caused by an increased conversion of cholesterol to bile acid.
Pauletzki
J
J
Department of Medicine II, Klinikum Grosshadern, University of Munich, Federal Republic of Germany.
Stellaard
F
F
Paumgartner
G
G
D000368:Aged; D001647:Bile Acids and Salts / Q000378:metabolism*; D002247:Carbon Isotopes; D002635:Chenodeoxycholic Acid / Q000493:pharmacokinetics; D002784:Cholesterol / Q000097:blood; D002793:Cholic Acids / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D001647:Bile Acids and Salts; D002247:Carbon Isotopes; D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; D002784:Cholesterol