Thyroid-stimulating Hormone Levels Are Inversely Associated With Serum Total Bile Acid Levels: a Cross-Sectional Study

Objective: Bile acids (BAs) synthesized from cholesterol play a critical role in eliminating excess cholesterol to maintain cholesterol homeostasis. BAs are also signaling molecules that are involved in the regulation of lipid, glucose, and energy metabolism. Thyroid-stimulating hormone (TSH) has been found to decrease liver BA synthesis via a sterol regulatory element-binding protein 2/hepatocyte nuclear factor 4 alpha/cholesterol 7α-hydroxylase (SREBP-2/HNF-4α/CYP7A1) pathway in vivo and in vitro. However, the relationship between serum TSH and total BA levels in humans is still unclear. Methods: This was a single-center cross-sectional study of 339 subclinical hypothyroidism (SCH) patients and an equal number of controls matched by age and sex from 11,000 subjects. Results: Serum total BA levels significantly decreased (3.11 ± 2.05 vs. 5.87 ± 2.39, P<.01), while total cholesterol (TC) levels increased (5.02 ± 0.65 vs. 4.88 ± 0.63, P<.01) in subclinical hypothyroidism (SCH) patients compared to control subjects. Serum TSH and BA levels were significantly and negatively correlated in subclinical hypothyroid patients who were also hypercholesterolemic (rs = -0.189, P = .004). Each 1 μIU/mL increase in TSH level was associated with a decrease in log-transformed values of total BAs (logTBAs) by 0.182 after controlling for confounding factors relevant to BA metabolism. The relationship between TSH and serum total BAs was more significant in subjects younger than 65 years. Conclusion: Our results suggested that TSH is correlated with the total BA level in SCH patients independent of thyroid hormone, which suggests a potential physiological role of TSH and the importance of maintaining normal range TSH in SCH patients. Abbreviations: BA = bile acid CYP7A1 = cholesterol 7α-hydroxylase FBG = fasting blood glucose HDL-C = highdensity lipoprotein cholesterol LDL-C = low-density lipoprotein cholesterol logTBAs = log-transformed values of total BAs SCH = subclinical hypothyroidism TC = total cholesterol TG = triglyceride TH = thyroid hormone TSH = thyroid-stimulating hormone