Thyroid hormone therapy in organ donors
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* Roberto Imberti
* Mariapia Vairetti

*   © 2007 Canadian Medical Association or its licensors

Sam Shemie and associates recommend that consideration be given to using thyroid hormone therapy in all organ donors.1 We have experimental data suggesting that administering thyroid hormones to hemodynamically stable organ donors could decrease the success of liver transplants.

In a model of ischemia–reperfusion (warm ischemia) in rats, we showed that pretreatment with thyroxine negatively affects the energetic status of the liver by reducing the preischemic and postreperfusion concentrations of adenosine triphosphate in the liver.2 We also observed that pretreatment with thyroxine reduces the liver tissue concentration of reduced glutathione, an intracellular antioxidant, and increases the susceptibility of isolated rat hepatocytes to anoxia and oxidative stress.2,3 Castilho and associates reported that 3,5,3'-triiodothyronine induces oxidative stress in isolated liver mitochondria, which leads to membrane thiol oxidation and inner membrane permeabilization.4 This process is known as the mitochondrial permeability transition and is characterized by swelling and depolarization of the mitochondria, resulting in an inability to produce adenosine triphosphate.4 There is evidence that hypothyroidism has generalized protective effects against anoxic ischemia and reperfusion injury, conditions that occur during organ storage and transplantation. In the rat, hypothyroidism reduces liver necrosis associated with cold storage, improves liver function and increases the concentration of reduced glutathione in the liver during reperfusion after cold storage;2,3 it also protects rat kidneys from ischemia.5

Although these experimental data were obtained in animals and cannot be directly applied to the clinical setting, they suggest that we should consider the possibility that administration of thyroid hormones might damage human liver tissue during organ harvesting, cold storage and transplantation and therefore should not be administered to all organ donors. It is also worth considering the possibility that pharmacological hypothyroidism might protect the organs of hemodynamically stable donors during cold storage and reperfusion.

## REFERENCES

1.  1. Shemie SD, Ross H, Pagliarello J, et al. Organ donor management in Canada: recommendations of the forum on Medical Management to Optimize Donor Organ Potential. *CMAJ* 2006;174(6 Suppl):S13-S30.
    
    

2.  2. Imberti R, Vairetti M, Gualea MR, et al. The effects of thyroid hormone modulation on rat liver injury associated with ischemia-reperfusion and cold storage. Anesth Analg 1998;86:1187-93.
    
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3.  3. Imberti R, Vairetti M, Silini E, et al. Effects of thyroid hormone modulation on rat liver injury associated with anoxia, oxidative stress and cold storage. Haematologica 1998;83(Suppl):46-7.
    
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4.  4. Castilho RF, Kowaltowski AJ, Vercesi AE. 3,5,3'-Triiodothyronine induces mitochondrial permeability transition mediated by reactive oxygen species and membrane thiol oxidation. Arch Biochem Biophys 1998;354:151-7.
    
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5.  5. Paller MS. Hypothyroidism protects against free radical damage in ischemic acute renal failure. Kidney Int 1986;29:1162-6.
    
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