Feline hyperthyroidism: parallels with human hyperthyroidism
Feline hyperthyroidism (FH) is the commonest endocrinopathy in cats. The mean age at presentation is 13 to 14 years of age, and the incidence has been estimated at 1 cat per 300 cats examined. Hyperthyroidism due to thyroid stimulating autoantibodies (a feline Graves disease) has not been reported in cats. FH is analogous, clinically and pathologically, to human toxic nodular goitre (HTNG), though there is no known sex predisposition in cats, unlike the female predisposition to HTNG. Treatment options for feline patients include medical management with thiamazole or carbimazole, thyroidectomy, or radiotherapy with 131I.
In both FH and HTNG, hyperthyroidism is caused by thyroid stimulating hormone (TSH) independent overactivity of hyperfunctioning hyperplastic/adenomatous thyroid nodules, resulting in high circulating concentrations of thyroid hormones. The aetiopathogenesis of both FH and HTNG is complex and multifactorial and is not fully elucidated. Dietary iodine (and possibly selenoprotein) levels impact on the frequency and molecular genetic lesions inf HTNG, and may be important in cats. Exposure to goitrogens may be particularly important in cats, as most goitrogens are metabolised by glucuronidation, a process that is particularly slow in cats.
Up to 82% of HTNG patients have gain-of-function TSH receptor gene mutations. We have recently demonstrated similar mutations in 67 of 134 nodules from 28 of 50 hyperthyroid cats. However, this is only one factor, and in both FH and HTNG, nodules from an individual patient or single thyroid lobe may harbour different mutations, and in some patients and glands, no such mutations are found. Interestingly, gsp mutations have been identified in autonomously functioning human adenomas but not in TNG, and their presence or frequency in FH has not been investigated. Ras mutations are a rare event in human TNG, and although ras over-expression is reported to be common in FH, we have not found K ras mutations in 25 patients evaluated so far.