Thyroid Auto‐immunity as a Disorder of Immunological Tolerance

Abstract

The immunological response to thyroid damage has been studied in the 101. thyrotoxic patients treated with radioactive iodine (1311). Patients who had positive titres of thyroid complement-fixing (CF) antibody in the sera before treatment invariably showed a rise in titre of this antibody commencing approximately 6 weeks after treatment but always falling to pre-treatment or lower levels after some months. Only in exceptional cases was there any formation of the thyroid CF antibody in patients who had negative thyroid CF tests before treatment; this was so even when the 1311 treatment was repeated on two, three or four occasions. In general, the change in thyroid CF titre was more pronounced than the change in titre of antibody to thyroglobulin.Although the epithelial cells of the human fectal thyroid are riclh in thyroid cytoplasmic antigen, the basement membrane is even more delicate than that noted in Hashimoto thyroiditis affecting the adult gland.A preliminary study has been made of the thymus in Hashimoto thyroiditis. Numerous germinal centres were observed in a thymic biopsy in one case and the radiological appearances of an enlarged thymus were noted in two others.These several findings are considered in terms of the possible meclhanisms of auto-inununity and the view is taken that formation of thyroid auto-antibodies is a result of a genetically determined disorder of immunological tolerance.

Episodic encephalopathy associated with thyroid disorders

“…It is generally accepted that myxoedema represents the end result of chronic thyroiditis (Hall, 1962), and that, although the aetiology of Hashimoto's thyroiditis is not fully known, there is evidence to suggest that it is a disorder secondary to an autoimmune process (Hall, 1962;Irvine, 1964). The presence of clinical features of more than one disorder thought to be due to autoimmune processes occurring in the same patient is well known, and Hashimoto's thyroiditis has been reported in association with other probable autoimmune disorders including myasthenia gravis (Simpson, 1960(Simpson, , 1964, pernicious anaemia (Tudhope and Wilson, 1960), rheumatoid arthritis (Buchanan et al, 1961), polymyositis (Sharvill, 1958), and systemic lupus erythematosus (White et al, 1961).…”

Pathogenesis of the Hyperthyroidism of Graves's Disease

“…The tendency for hyperthyroidism to remit during pregnancy (Munro, 1964) (Roitt and Doniach, 1960). The titre of thyroid antibodies rises transiently after l"1I therapy, which apparently intensifies the antigenic stimulus (Irvine, 1964). I and others have observed L.A.T.S.…”

“…of its thyroid-stimulating property. Irvine (1964) has observed that while irradiation with "'I consistently increases the titre of detectable thyroid antibodies, it has little tendency to provoke the appearance of thyroid antibodies not already detectable. This suggests that the ability to form the various thyroid antibodies in response to the appropriate antigenic stimulus is not universal, but is confined to certain individuals.…”

The aetiology and pathogenesis of hyperthyroidism

“…There is also a clinical association between thyrotoxicosis and Addison's disease in that Blizzard & Kyle (1963) found three cases of thyrotoxicosis in a series of sixty-eight patients with non-tuberculous Addison's disease. Irvine (1964) found two thyrotoxic patients in a series of fifteen cases of Addison's disease thought to be non-tuberculous. In one personal case thyrotoxicosis and exophthalmos preceded clinical Addison's disease by 15 years.…”

“…In the light of all these data it would seem likely that thyrotoxicosis together with other diseases such as Hashimoto's disease and rheumatoid arthritis may arise as a genetically determined disturbance of immunological tolerance (Mackay & Burnet, 1963;Irvine, 1964). In this connection it is of interest that medullary lymphoid follicles have been shown in the thymus in cases of thyrotoxicosis but not in cases of non-toxic goitre.…”