Pathological anatomy of thyrotoxic liver

The work was performed on experimental material. An experimental model of thyrotoxicosis in laboratory animals, white male rats, was obtained by daily administration оf l-thyroxine at a dose of 1.6 mg per 1 kg of body weight. The duration of the experiment was 45 days. 67 mature rats weighing 250–300 g were selected for the experiment. Rats were removed from the experiment after 7, 14, 21, 28, 35 and 45 days. As a control, we used 22 rats that were not injected with L-thyroxine. The level of thyroid hormones in the blood of rats was determined by enzyme immunoassay. A macroscopic study was performed and the size and mass of the rat liver were determined. For histological examination, pieces of liver tissue were taken, and they were fixed in 10 % buffered formalin for 10 days. Histological preparations were prepared by the standard method, using histological, histochemical and immunohistochemical studies. The results of the study showed that in experimental thyrotoxicosis, the level of thyroid hormones increases: T3 (triiodothyronine) equals 21.37 ± 0.03 mmol/l, 4.75 ± 0.02 mmol/l in the control; T4 (thyroxine) equals 2.55 ± 0.03 mmol/l, 1.80 ± 0.03 mmol/l in the control. Macroscopic examination revealed a 2-fold increase in the size and weight of the liver. Histological examination revealed widespread interstitial edema of the liver stroma, dystrophic and destructive changes, necrosis of hepatocytes, formation of cavities, thinning and atrophy of the liver beams, lymphocytic infiltration. The immunohistochemical study shows a decrease in Ki-67 expression level to 1.8 % compared to the control (5.0 %), which indicates a decrease in reparative processes in the liver.

Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study

Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT4 levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT4, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.