| ObjectiveBile acids (BAs) are a family of steroidal molecules derived from cholesterol and biosynthesised in the pericentral hepatocytes of the liver. Traditionally BAs are known for their ability to act as soluble agents in the gut, aiding in the absorption of dietary lipids through the formation of mixed micelles. However the identification of BAs as ligands of the farnesoid X receptor (FXR) has lead to the realization that these molecules have a wider range of biological effects. BAs regulate lipid and glucose homeostasis such as activation of the FXR and/or the G-protein coupled receptor, TGR5. They can activate signaling pathways including apoptotic, inflammatory and carcinogenic. The important role that thyroid hormones had played in bile acids metabolism has been confirmed.Due to the associated hypercholesterolaemia, bile acid kinetics in hypothyroidism dysfunction has attracted the attentions of many investigators. Although conflicting reports have appeared concerning the relationships of bile acid patterns to human thyroid dysfunction, there are no published convincing and elaborate data on serum bile acids in the patients with thyroid dysfunction. The aim of this study was to clarify the potential effects of thyroid function on the serum bile acids profile in human beings and to find if there exist an association between thyroid dysfunction and the changes of serum bile acid.Methods Nine patients with hyperthyroidism, eight patients with hypothyroidism and eight subclinical hypothyroidism patients, all female, were studied. The healthy control involved eleven healthy volunteers with normal thyroid fanction. All the subjects are all from Shandong Province Hospital. No subjects had clinical evidence of liver, bowel, and gallbladder diseases and diabetes. Their B ultra examinations were within normal range. Informed consent was obtained from all subjects.The concentrations of five representative bile acids were measured by the stable and accurate HPLC-MS/MS method.ResultsIn a single chromatographic run, the five bile acids, were determined simultaneously. A linear correlation over a wide range of bile acid concentrations (3.9-3000ng/ml) was observed. The recovery period for all the analyzed bile acids was39.87-110.66%. The detection limit was about2-4ng/ml.By Mann-Whitney test, we find that the UDCA concentration was significantly75%lower in patients with hyperthyroidism than in hypothyroidism patents (p=0.003). The UDCA concentration in patients with hypothyroidism was42.86%higher than that of subclinical hypothyroidism patents (p=0.006), and was significantly70%higher in healthy controls than in hyperthyroidism patents (p=0.03). The DCA concentration in sera of patients with hyperthyroidism was80.26%lower than that of hypothyroidism patents (p=0.011) and66.%lower than in that of healthy controls (p=0.027). The DCA concentration in patients with hypothyroidism was55.1%higher than that of subclinical hypothyroidism patents (p=0.001). We find that the CA concentration was significantly88.16%lower in patients with hyperthyroidism than in hypothyroidism patents (p=0.002) and it was significanty70%lower in healthy controls (p=0.009). The ratio of the sum of CA and DCA to that of LCA and CDCA (CA+DCA/LCA+CDCA) was significantly71.57%lower in patients with hyperthyroidism than in hypothyroidism patents (p=0.001). The ratio in patients with subclinical hypothyroidism was71.76%lower than that of hyperthyroidism patents (p=0.043), and was significantly43.53%higher in healthy controls than in hyperthyroidism patents (p=0.009). The ratio in healthy controls was59.20%lower than that of hypothyroidism patents (p=0.002), and was significantly51.1%lower in patients of subclinical hypothyroidism than in hypothyroidism patents (p=0.009). The sum concentration of these five bile acids, including CA、UDCA、CDCA、DCA and LCA, hyperthyroidism was79.93%lower than that of hypothyroidism patents (p=0.003) and70.00%lower than in that of healthy controls (p=0.014).The sum concentration in subclinical hypothyroidism patients was66.91%lower than that of hyperthyroidism patents (p=0.027)The concentration of UDCA、CA、CDCA、DCA and the sum concentration of the five bile acids in sera all had a positive correlation with the TSH concentration (rs>0.25, p<0.05). But LCA concentration didn’t correlated to the concentration of TSH.ConclusionWe find that thyroid disorders do have an effect on bile acids metabolism. The concentration of UDCA、CA、CDCA、DCA and the sum concentration of the five bile acids had a positive correlation with that of TSH. Though the mechanism is still uncertain, the determination of these bile acids in serum will provide a useful means for monitoring therapy progress and bring forth new ideas for researches in thyroid related diseases. |
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