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Small Animal Hospital, Department of Veterinary Clinical Science, University of Liverpool, Crown Street, Liverpool, Merseyside L7 7EX, UK
¹ Department of Veterinary Pathology, University of Liverpool, Crown Street, Liverpool, Merseyside L69 7ZJ, UK

(Requests for offprints should be addressed to L Blackwood; Email: L.Blackwood{at}liverpool.ac.uk)

Hyperthyroidism is the most common endocrinopathy in cats, and is both clinically and histopathologically very similar to human toxic nodular goitre (TNG). Molecular studies on human TNG have revealed the presence of mis-sense mutations in the thyroid-stimulating hormone receptor (TSHR) gene, most frequently in exon 10. Our hypothesis was that similar mutations exist in hyperthyroid cats. Genomic DNA was extracted from 134 hyperplastic/ adenomatous nodules (from 50 hyperthyroid cats), and analysed for the presence of mutations in exon 10 of the TSHR gene. 11 different mutations were detected, one silent and 10 mis-sense, of which nine were somatic mutations. 28 of the 50 cats (67/134 nodules) had at least one mis-sense mutation. The mis-sense mutations were Met-452Thr in 17 cats (35 nodules), Ser-504Arg (two different mutational forms) in two cats (two nodules), Val-508Arg in one cat (three nodules), Arg-530Gln in one cat (two nodules), Val-557Leu in 13 cats (36 nodules), Thr-631Ala or Thr-631Phe (each mutation seen in one nodule of one cat), Asp-632Tyr in six cats (10 nodules) and Asp-632His in one cat (one nodule). Five of these mutations have been associated previously with human hyperthyroidism. Of the 41 cats for which more than one nodule was available, 14 had nodules with different mutations. The identification of a potential genetic basis for feline hyperthyroidism is novel, increases our understanding of the pathogenesis of this significant feline disease, and confirms its similarity to TNG.