Investigations on Etiopathogenesis
Since reports of feline hyperthyroidism (HT) began to appear from around the world in 1980, this disease has become the most
common endocrinopathy in cats. The age-specific prevalence of feline HT has increased between 1978 and 1997. Cats are the
only nonhuman mammalian species with a high incidence of HT. Two mechanisms underlying the possible pathogenesis of this disease
have been explored: an autoimmune-related mechanism (similar to toxic nodular goitre [TNG] in humans) or intrinsic autonomy
of the growth and function of follicular cells. Experimental support for an immune etiology is lacking as autoantibodies are
not found in affected cats. Therefore, investigations have focused on possible host factors and/or environmental reasons for
intrinsic autonomy of thyroid follicular function. None of the studies to date have isolated a single dominant factor that
could be universally incriminated in the development of hyperthyroidism in cats. Many authors believe that hyperthyroidism
is a multifactorial disease in this species.
Somatic mutations in the G(s alpha) gene or in exon 10 of the thyroid-stimulating hormone (TSH) receptor gene have been identified
in a few HT cats, providing an interesting parallel to TNG, but failing to account for the majority of cases of feline HT.
Decreased expression of an inhibitory subset of guanosine triphosphate-binding proteins [G(i2) proteins] may help explain
the molecular mechanism of feline HT but fails to provide information about etiology.
Extrinsic factors strongly or consistently associated with HT in case-control studies include: using cat litter, eating a
diet composed mainly of canned food particularly fed from pop-top cans, living in a single-cat household, sleeping on the
floor, and regular treatment of cat bedding with anti-flea products. In evaluating such results, it is important to remember
that epidemiological studies cannot prove causality (show the direction of an association). In addition, factors demonstrating
an association with HT could be confounded by a factor not examined in the survey. Most recently, interest has focused on
the results of an epidemiologic study showing an association between HT and exposure to the flame-retardant chemicals, polybrominated
diphenyl ethers (PBDEs) in canned cats foods or household dust. These intriguing results, however, fail to provide a logical
explanation as to why cats are predisposed to HT if they live close to an ocean or one of the Great Lakes in North America
, why cats of specific breeds are protected from developing this disease, and why colony cats with no exposure to carpets
or furniture also have a high incidence of HT. Environmental iodine concentrations are much higher in regions in close proximity
to the ocean. Iodine intake, however, which has a well-established causal relationship with goitre in humans, has failed to
show a relationship to HT in cats. Purebred cats, especially Siamese and Himalayan cats, are at significantly lower risk of
developing HT than domestic short- or long-haired cats. Speculation has focused around a possible genetic basis for this protective
effect. Another explanation is that light coat color is protective. Tyrosine, the amino acid that is the precursor to melanin,
the dark pigments in skin or hair (regardless of actual coat color), is also the precursor to thyroid hormone, as thyroxine
(T4) contains the amino acid tyrosine in the center, surrounded by four iodine molecules. No studies have been published evaluating
tyrosine intake and thyroid function.
Based on current evidence, the etiology of HT in cats is thought to be multifactoral. An immune mechanism or genetic mutation
have been largely excluded from further consideration.