Thyroid Growth Immunoglobulins in Feline Hyperthyroidism

Abstract

Feline hyperthyroidism bears a strong clinical and pathologic resemblance to toxic nodular goiter in humans. To evaluate whether the observed thyroid growth might be due to circulating thyroid antibodies, as has been postulated in humans, we studied the effect of purified immunoglobulin (Ig) G preparations on a rat thyroid follicular (FRTL-5) cell line. When compared with control, hyperthyroid cat IgG caused significantly increased [3H]-thymidine (Tdr) incorporation into DNA (p less than 0.02) and stimulated cellular proliferation 15-fold. Stimulation of 3H-Tdr incorporation tended to be biphasic and could be inhibited completely by a potent, specific TSH receptor blocking antibody. Hyperthyroid cat IgG also significantly inhibited 125I-bTSH binding to porcine thyroid membranes, an effect that could be reproduced using electrophoretically pure IgG and normal cat thyroid membranes. Unlike its effect on growth, hyperthyroid cat IgG did not stimulate intracellular cAMP, and there was no correlation between thyroid function in vivo and IgG growth-promoting activity in vitro. These data suggest that elevated titers of thyroid growth IgGs, probably acting through the TSH receptor, are present in feline hyperthyroidism and may play a role in goiter formation. Unlike growth, the thyroid hyperfunction observed is not IgG dependent. Further study of feline hyperthyroidism may contribute important insights into human nodular goiter and into the mediation of thyroid growth in general.

ANIMAL MODELS OF DISEASE: Feline hyperthyroidism: an animal model for toxic nodular goiter

“…Although cats with toxic nodular goiter do not have circulating TSIs, high titers of serum thyroid growthstimulating immunoglobulins (TGIs) have been measured in hyperthyroid cats (Brown et al 1992). These autoantibodies, which act to promote thyroid growth but not to stimulate thyroid hormone secretion, also have been reported in human patients with toxic nodular goiter, as well as in patients with Graves' disease, Hashimoto's thyroiditis, and euthyroid goiter (Brown 1995).…”

Thyrotropin-Stimulated DNA Synthesis and Thyroglobulin Expression in Normal and Hyperthyroid Feline Thyrocytes in Monolayer Culture

“…In humans, the most common hyperthyroid disease, Graves' disease, is immune-mediated and results from stimulatory TSH receptor antibodies resulting in constitutive activation of thyroid cells and thyrotoxicosis (28). Several groups have investigated a similar pathogenesis for the feline disease, but have been unable to demonstrate thyroid autoantibodies or any effect of hyperthyroid cat sera on rat FRTL-5 cell lines (16,17). In addition, a recent report showed no activation of cloned cat TSH receptors in response to treatment with sera or purified IgG from hyperthyroid cats (18).…”

“…It has been theorized that weak stimulation of these highly functioning cells causes them to become autonomous (8,10) The pathogenesis of feline hyperthyroidism is unknown. Although investigated, no immune-mediated basis for the disease has been proven, suggesting that its pathogenesis is unlike that of Grave's disease in people (15)(16)(17)(18). Similar to histological findings in TNG, thyroids from hyperthyroid cats consist of multiple hyperplastic nodules of active thyroid tissue surrounded by inactive paranodular tissue (3,15,19).…”

Autoimmune thyroiditis — spontaneous disease models — cat: critical comments

“…These observations would imply that immunity to the TSH-receptor plays a preponderant role in a subgroup of patients with thyroid autoimmunc disorders and either hypothyroidism or hyperthyroidism (Chiovato et al, 1994). In this regard it is relevant to recall that, while no spontaneous animal model of Graves' disease has been described so far, the existence of a TSH-receptor antibody with growth promoting activity has been reported in cats with toxic nodular goiter (Brown et al, 1992). In view of the above observations one could speculate whether cats are more prone to TSH-R autoimmunity than any other species apart from humans.…”