Graves' ophthalmopathy is probably the most difficult management problem for the thyroidologist. This review aims to highlight recent advances in our knowledge of the condition in the fields of diagnosis, aetiology and treatment, but it will become apparent that much remains to be understood of the aetiology of Graves' ophthalmopathy which consequently impairs optimal management of the condition.
DiagnosisThe presence of characteristic eye signs, namely periorbital oedema, chemosis, injection of the sclerae, exophthalmos, lid retraction and ophthalmoplegia in any combination, together with hyperthyroidism, present no difficulty in diagnosis. Problems may arise however if the patient is not and has not been thyrotoxic, in which case the condition is termed ophthalmic Graves' disease (OGD); in this subgroup the signs are often unilateral, raising the possibility of a retro-ocular space-occupying lesion in the differential diagnosis.
Biochemical investigationsIn OGD thyroid hormone levels (total or free) by definition are not elevated. However, it should be remembered that patients with Hashimoto's thyroiditis may have eye signs which are also covered by the term OGD (Ormston et al. 1973), so that T3 and T4 may be either normal or low in OGD and occasionally minor elevations of free T3 levels are seen in OGD (Teng & Yeo 1977). In a sequential study of 27 euthyroid patients with OGD followed for three years, one became hyperthyroid and 7 hypothyroid (Teng & Yeo 1977) and therefore long-term follow up of euthyroid OGD patients is important.The TSH response to TRH is abnormal in about half of the patients with OGD, being impaired or absent in 40% and exaggerated in 7% (Teng & Yeo 1977). As expected, a close correlation was also found in this study between T3-induced suppression of thyroidal radioactive iodine uptake and the results of the TRH test, so that the latter alone will suffice as a diagnostic test.
Immunological investigationsThyroglobulin and microsomal antibodies occur in about 75% of patients with OGD, reflecting in part the presence of Hashimoto's thyroiditis in some of these subjects. Such antibodies are readily measured and are valuable markers for OGD. TSH receptor antibodies, measured by their displacement of radiolabelled TSH from its thyroid receptor in vitro, are positive in 40% of OGD patients ) and thyroid-stimulating antibodies, measured by the thyroid slice-cAMP release assay, were found in all 6 patients tested with OGD and an impaired TSH response to TRH; 4 subjects with OGD and a normal TRH test did not have such antibodies (Zakarija et al. 1980). The use of such assays adds little to the diagnostic information more easily available from the TRH test and tests for conventional thyroid autoantibodies.