Altered thyroid status modulates portal pressure in normal rats

Background & Aims: Disturbances in thyroid function in humans and experimen tal animal models have been associated with alterations in liver function a nd portal circulation. We have previously shown that hypothyroidism can sig nificantly reduce portal pressure in portal vein ligated rats as well as in hibit the development of cirrhosis and fulminant hepatic failure following toxic liver injury. The aim of this study was to determine the effects of i ncreased and decreased thyroid function on portal pressure in rats with nor mal liver histology and portal circulation. Methods: Three groups of 12 Wis tar rats each were studied over a 30 day period: euthyroid (Group 1), hyper thyroid (Group 2) and hypothyroid (Group 3). Hyperthyroidism was induced by subcutaneous injection of triiodothyronine (400 mu g/100g body weight) eve ry ten days during the study period. Hypothyroidism was induced by methimaz ole (0.04% in drinking water) from 2 weeks prior to and throughout the 30 d ay study. Serum triiodothyronine (T3) and thyroid stimulating hormone (TSH) levels were determined to confirm the induction of hyper- and hypothyroidi sm. Portal pressure was assessed by direct catheterization of the portal ve in prior to sacrifice. Indirect confirmation of changes in portal circulati on was obtained by determining splenic weight at the time of sacrificing th e animals. Animals were sacrificed at 10 day intervals throughout the 30 da y study. Results: Triiodothyronine treated rats were hyperthyroid compared to controls, with an elevation in serum T3 levels (3.8+/-0.9 mmol/L vs 1.3/-0.4 mmol/L, p<0.05). In rats treated with methimazole, hypothyroidism was confirmed by a 7-fold increase in serum TSH compared to controls (1.8+/-0. 4 vs 0.24+/-0.04 mmol/L, p<0.01). Portal pressure was significantly higher in the triiodothyronine treated rats compared to controls (12.8+/-1.7 and 9 .6+/-0.75 cm H2O, p<0.001). Splenic weights in hyperthyroid rats were signi ficantly higher than in controls (579+/-44 vs 478+/-46 mg, p<0.01). Portal pressure was significantly lower in the methimazole treated group compared to the control group (8.13+/-0.68 vs 9.6+/-0.75 cm H2O, p<0.01) as were spl enic weights (400+/-33 vs 478+/-46 mg, p<0.01). Conclusion: These studies d emonstrate that disturbed thyroid function exerts significant hemodynamic e ffects on the portal circulation in normal rats and complements results fro m previous similar studies in cirrhotic animals.