A Mutational Pathway Leading to Thyroid Tumors During Medication for Feline Hyperthyroidism

Abstract

Over 350 million cats worldwide live in homes with their human companions. An inexplicable phenomenon is affecting domestic cats (felis catus) - the global prevalence of feline hyperthyroidism has been increasing since the late 1970s. Feline hyperthyroidism is the result of a malignant thyroid carcinoma in ~2% and a benign functional thyroid adenoma in ~98% of diagnosed cases. Thyroid tumors remain palpable in cats after medication (e.g., methimazole, carbimazole), but few studies have reported such remaining tumors. Hence, we pathologically examined tissues that were sampled from 206 cats by thyroidectomy after such medication at 65 veterinary hospitals. Our results show carcinoma in 11.2% and adenoma in 83.4% of samples. Based on an increase in the carcinoma rate from ~2% at the diagnosis stage to 11.2% at the post-treatment stage, it can be inferred that a thyroid adenoma transforms into a thyroid carcinoma in a hyperthyroid cat through a multistep mutational pathway like the human adenoma-carcinoma sequence. It remains for future study to assess whether this feline phenomenon is somehow related to the human one in terms of the One Health approach; e.g., the incidence rate of thyroid cancers has been increasing in humans since the early 1980s (cf. this tendency cannot be explained only by over-diagnosis and detection technology).