Bile acid metabolism in human hyperthyroidism

Abstract

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.

Regulation of bile acid synthesis

“…Other hormones may affect activity of cholesterol 7a-hydroxylase. For example, thyroid hormone increases but thyroidectomy decreases activity of this enzyme (76). In human hyperthyroidism, CA and total bile acid synthesis were suppressed.…”

A Distinct Thyroid Hormone Response Element Mediates Repression of the Human Cholesterol 7α-Hydroxylase (CYP7A1) Gene Promoter

“…Protected regions (Site II and Site III) are indicated by the vertical lines at the right. However, Pauletzki et al (35) also documented a 20% decrease in total primary bile acid synthesis. C, Labeled double-stranded oligonucleotides corresponding to TRE, Site II, or Site III (see Table 1) were incubated with recombinant TR␣ and RXR␣.…”

Hypothyroidism and dyslipidemia: Modern concepts and approaches

“…Thyroid hormone is known to play a role in the regulation of bile acid synthesis. However, this is unlikely to be a primary mechanism for lipid changes in patients with thyroid dysfunction [9].…”