Autoimmunity in the pathogenesis of endocrine exophthalmos

Abstract

It is now fully acceptable that thyroid stimulating antibodies (TSAb) include long-acting thyroid stimulator (LATS) which stimulates the thyroid and adrenal glands in the mouse (El Kabir et al, 1971) and other animals but may have no effect on the human glands, and LATS-protector (LATS-P) or human-specific thyroid-stimulating antibody (HTS) which is probably responsible for the hyperactivity of the thyroid in Graves' disease (Adams, Kennedy and Stewart, 1974; Adams et al, 1974). As in other autoimmune systems there is a larger group of closely allied antibodies, reactive with TSHsensitive receptors in other tissues. Particularly important in this respect are the ophthalmopathic immunoglobulins (O-Ig) which cross-react with the harderian gland in guinea pigs and with adipose tissue cells in several species including man. Such antibodies are cell-stimulating in character as opposed to being cytotoxic, as are thyroid microsomal antibodies. They could be responsible for the proliferation of retro-orbital tissue in exophthalmos; related but not identical antibodies might cause subcutaneous lesions in pretibial myxoedema. There are indications that fibroblasts also proliferate in the orbit and other sites in these conditions but it is uncertain that TSHreceptors exist on connective tissue cells so their stimulation could be due to other mechanisms related to inflammation and repair. Two separate lesions in endocrine exophthalmos are the myositis of the extraocutar muscles and the increased bulk of retrobulbar fat and/or connective tissue. Together these lesions give rise to the diplopia, raised orbital pressure, oedema and proptosis characteristic of the syndrome (Werner, 1972). Autoimmune mechanisms of a different nature are probably involved in the two types of dysfunction. Other factors such as venous stasis play a part in the clinical picture but will not be discussed. The spasm of the levator palpebrae muscle which causes lid retraction and lid lag, is still attributed to the effects of excess circulating thyroid hormones and adrenergic potentiation, and has not so far been implicated immunologically.