Evidence for an Effect of Antithyroid Drugs on the Natural History of Graves' Disease

Abstract

In the United Kingdom, about half the patients with Graves' disease who are given antithyroid drugs are still in remission one year after treatment is stopped. The most widely held view is that such remission rates are due only to the biochemical effects of the drugs, the disease either spontaneously remitting or abating when the immune system is no longer subject to the stimulatory effects of excessive thyroid hormone. We review here the accumulating evidence against both of these alternatives. In contrast, there is now a large body of work which shows that thyrotrophin receptor antibody levels, central to the aetiology of Graves' hyperthyroidism, fall during antithyroid treatment and that remission may be related to this fall in a fashion which is dependent on the dose and duration of treatment. This immunosuppressive effect is supported by experimental data and on the basis of these results we propose that antithyroid drugs may modify the natural history of Graves' disease and contribute to the remission which occurs in a proportion of treated patients.

Thymic hyperplasia in patients with Graves' disease. Identification of thyrotropin receptors in human thymus.

“…The decrease in thymic size and density by treatment with antithyroid drugs could be produced, at least in part, by an indirect action by lowering circulating thyroid hormone levels, since it has been reported that exogenous thyroid hormone administration to experimental animals resulted in enlargement of both cortical and medullary components of the thymus (29,30), while thyroidectomy induced a reduction of thymic size (31). It has also been suggested that antithyroid drugs not only cause a block of thyroid hormone synthesis, but also have immunosuppressive effects, including lowering TSHreceptor antibody levels (32). Thus, antithyroid drugs might also induce thymic atrophy by mechanisms related to their immunosuppressive effects.…”

Increased serum CXCL10 in Graves’ disease or autoimmune thyroiditis is not associated with hyper- or hypothyroidism per se, but is specifically sustained by the autoimmune, inflammatory process

“…Therefore, the significant decrease in serum CXCL10 after restoration of euthyroidism in GD patients reported here could be reasonably ascribed to the well-known immunomodulatory effect of antithyroid drugs. In fact, besides its ability to decrease thyroid hormone production (28), MMI appears to interfere with the immunologic abnormalities in GD hyperthyroidism, as shown by the 50% of patients successfully cured by the drug and by the significant decrease of serum antithyroid antibodies observed in most treated patients (28,29). Therefore, these drugs may have influenced chemokine levels, especially as the same drugs can reduce cytokine expression by TFC with a final effect of reducing infiltration into the gland (30).…”

Role of Chemokines in Endocrine Autoimmune Diseases

“…MMI, besides its ability to decrease thyroid hormone production (138), has been shown to interfere with some immunological abnormalities typical of Graves' hyperthyroidism. The immunosuppressive effect of MMI is highlighted by the reduction of circulating thyroid antibodies, which occurs during medical treatment with this drug, and by the consistent percentage (nearly 30%) of Graves' patients entering prolonged remission after a course of medical therapy (138,139). These immunological effects of MMI might be mediated, at least in part, by an action on chemokine production, resulting in a decreased lymphocytic infiltration of the gland.…”