Introduction. Previously we have shown an increased prevalence of diagnosed hypothyroidism in common bile duct (CBD) stone patients, compared to gall bladder (GB) stone patients or age, sex and hospital admission adjusted controls. In vitro we have shown that thyroxine (T4) has a spesific, prorelaxing effect on Sphincter Oddi (SO) contractility (Gastroenterology 1998;114:2135). The lack of this prorelaxing effect might explain the increased prevalence of CBD stones in hypothyroidism. We have also shown that hypothyroidism is associated with some changes in the biliary dynamics in human with GB in situ (Gastroenterology 2000;118:1024). The aim of the present study was to investigate biliary dynamics in relation to altered thyroid gland function in rat, which offers a good model due to absence of GB.
Material and Methods. 13-week Spraque-Dawley male rats were used. Euthyroid rats (n=30) had normal diet, hypothyroid rats (n=30) had thiouracil, and hyperthyroid rats (n=30) thiouracil and T4 in feed and water for 4 weeks. At 4 weeks 0.7 ml 99Tc-HIDA was injected IV. Blood pressure (BP) was measured directly from a. carotis. 10 rats from each diet group were sacrificed after 15, 45, or 60 min from Tc-HIDA injection. Liver and intestine were dissected off and blood sample was taken. Tissue radioactivity was measured with gammacounter and serum free T4 (S-FT4)level was measured with immunochemiluminometric assay. Amount of bile flow to intestine was determined by counting the relative intestine vs. liver Tc-HIDA activity in each animal.
Results. S-FT4 was 4.8±0.2, 47.6±1.6 and >80 pmol/l in hypo-, eu-, and hyperthyroid rats, respectively (mean±sem). In the beginning of experiment BP did not differ between the groups. Highest Tc-HIDA activity of liver was measured at 15 min in each group. Tc-HIDA flow from liver to intestine was slower in hypothyroid rats compared to euthyroid rats at 15 min (relative activity intestine vs. liver 4.1±0.6 vs. 7.3±0.9; p=0.01 (mean±sem)) and at 45 min (15.5±1.8 vs. 27.0±3; p=0.004). At 60 min Tc-HIDA flow was faster in hyperthyroid rats compared to euthyroid and hypothyroid rats (31.8±1.7 vs. 18.4±2.3 vs. 15.0±2.7; p=0.005 and 0.002, respectively).
Conclusions. Bile flow from liver to duodenum is reduced in hypothyroidism and enhanced in hyperthyroidism in rat lacking GB. This, together with our previous finding of inhibitory T4 effect on SO contractility, highly supports our suggestion that one important mechanism of induction of hypothyroidism associated CBD stones is reduction in bile flow.
