Examination of the eye muscles in biopsy and autopsy material has shown prominent fibroblasts, many degenerated fibers, and infiltrations of lymphocytes, mononuclear leukocytes, and lipocytes; hence the term infiltrative ophthalmopathy. These histopathologic findings are suggestive of an autoimmune disease—a hypothesis supported by the finding of serum antibodies that react (inconsistently) with extracts of eye muscles (Kodama et al). Possibly the antibodies target glycosaminoglycans of the orbital fibroblasts. A sensitivity of muscle fibers to beta-adrenergic activity caused by excessive thyroid hormone has also been postulated. Other factors are almost certainly involved, such as the small size of oculomotor motor units, the absence of dystrophin, and the rich mitochondrial content.
Treatment Because the ophthalmoparesis often runs a self-limited course, as does the exophthalmos, therapy is difficult to evaluate. Certainly the maintenance of a euthyroid state seems desirable (Dresner and Kennerdell). If the exophthalmos is slight, topical applications of adrenergic blocking agents (guanethidine eye drops, 5 percent) and ophthalmic ointment to prevent corneal drying are adequate. Severe exophthalmos, marked by periorbital and conjunctival edema, and the extraocular muscle weakness may be partially controlled by high doses of corticosteroids (about 80 mg/d prednisone). Because of the hazards of protracted corticosteroid therapy, this approach should be reserved for patients who would otherwise require surgical intervention to decompress the contents of the orbit. In a number of such cases, it has been possible for the patient treated with corticosteroids to weather the crisis for several weeks or more and avoid the damaging effects of extreme exophthalmos and risks of surgery. Exophthalmos of a degree that threatens to injure the cornea or cause blindness requires tarsorrhaphy or decompression by removal of the roof of the orbit.
This disorder closely resembles familial hypokalemic periodic paralysis (as described in Chap. 46). It consists of attacks of mild to severe weakness of the muscles of the trunk and limbs; usually the cranial muscles are spared. The weakness develops over a period of a few minutes or hours and lasts for part of a day or longer. In some series of patients with periodic paralysis, as many as half have had hyperthyroidism and most of them have been Asian males. Unlike the typical hypokalemic form, thyrotoxic periodic paralysis is not a familial disorder and its onset is usually in early adult life. Nevertheless, in most of the thyrotoxic cases, the serum potassium levels have been low during the attacks of weakness and the administration of 100 to 200 mg of potassium chloride has terminated the episodes. Propranolol in doses of 160 mg daily in divided doses is also helpful in preventing the episodes. More importantly, effective treatment of the hyperthyroidism abolishes the periodic attacks of weakness in more than 90 percent of cases. A mutation in the potassium channel, Kir2.6, has been found to confer susceptibility to the disease. Other aspects of periodic paralysis are discussed in Chap. 46.