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Title: Investigations into the pathogenesis and management of hyperthyroidism and thyroid hormone deiodination in the domestic cat
Author: Foster, D. J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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Since L-triiodothyronine (T3) is the hormone responsible for the major clinical manifestations of thyrotoxicosis, investigations are here reported into the hepatic, renal and thyroidal expression of type 1 iodothyronine deiodinase (IDI), the selenoenzyme responsible for conversion of L-thyroxine (T4) to T3 in these tissues. Studies were carried out into the possible role of thyroid stimulating immunoglobulins, selenium status and somatic mutations of the thyrotropin receptor (TSHR) in the pathogenesis of the disease. Using feline thyrocytes, Chinese hamster ovary cells expressing human TSHR (JPO9) and the rat thyrocyte cell line FRTL-5, no populations of immunoglobulins were detectable in the sera of hyperthyroid cats which stimulated cAMP production, displaced TSH binding from its receptor or induced growth compared to euthyroid cats. The plasma selenium status of cats from areas with high (Edinburgh and Sydney) and low (Denmark and Perth) incidences, respectively, of hyperthyroidism were not significantly different from each other. Cats however, have plasma selenium concentrations and red blood cell glutathione peroxidase activities which are approximately 10 times those of selenium replete rats and humans. In 11 hyperthyroid cats; the DNA for the TSHR region between codons 480 and 640 (the most common site for somatic mutations in human toxic nodular goitre) were not found to contain any such mutations. The mainstay of presurgical treatment for hyperthyroidism is the use of carbimazole, a drug which is not well-tolerated by approximately 8 per cent of affected cats. A combination of propranolol and potassium iodate was found to normalise heart rates, serum T3, and to a lesser extent T4 concentrations in a significant number of cats and may be used as an alternative presurgical treatment in those cats which cannot tolerate carbimazole.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available