Altered thyroid status modulates portal pressure in normal rats.
OBJECTIVE
Disturbances in thyroid function in humans and experimental animal models have been associated with alterations in liver function and portal circulation. We have previously shown that hypothyroidism can significantly reduce portal pressure in portal vein ligated rats as well as inhibit the development of cirrhosis and fulminant hepatic failure following toxic liver injury. The aim of this study was to determine the effects of increased and decreased thyroid function on portal pressure in rats with normal liver histology and portal circulation.


METHODS
Three groups of 12 Wistar rats each were studied over a 30 day period: euthyroid (Group 1), hyperthyroid (Group 2) and hypothyroid (Group 3). Hyperthyroidism was induced by subcutaneous injection of triiodothyronine (400 microg/100g body weight) every ten days during the study period. Hypothyroidism was induced by methimazole (0.04% in drinking water) from 2 weeks prior to and throughout the 30 day study. Serum triiodothyronine (T3) and thyroid stimulating hormone (TSH) levels were determined to confirm the induction of hyper- and hypothyroidism. Portal pressure was assessed by direct catheterization of the portal vein prior to sacrifice. Indirect confirmation of changes in portal circulation was obtained by determining splenic weight at the time of sacrificing the animals. Animals were sacrificed at 10 day intervals throughout the 30 day 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 significantly 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 splenic weights (400+/-33 vs 478+/-46 mg, p<0.01).


CONCLUSIONS
These studies demonstrate that disturbed thyroid function exerts significant hemodynamic effects on the portal circulation in normal rats and complements results from previous similar studies in cirrhotic animals.
Oren
R
R
Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Israel.
Dotan
I
I
Brill
S
S
Jones
B E
BE
BenHaim
M
M
Sikuler
E
E
Halpern
Z
Z
D000284:Administration, Oral; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007279:Injections, Subcutaneous; D008713:Methimazole / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D017082:Portal Pressure / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013961:Thyroid Gland / Q000187:drug effects / Q000503:physiopathology*; D013972:Thyrotropin / Q000097:blood; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology
D013956:Antithyroid Agents; D014284:Triiodothyronine; D008713:Methimazole; D013972:Thyrotropin