Epidemiology
  A recent population-based cohort study in Olmsted County, Minnesota has provided reliable epidemiological data (Bartley et al. 1995). The overall age-adjusted incidence rate of GO for women was 16.0 cases and for men 2.9 cases per 100,000 population per year. Incidence rates exhibited an apparent bimodal peak (in the age groups 40 to 44 years and 60 to 64 years in women, and 45 to 49 years and 65 to 69 years in men). Male sex and older age (over 60 years) are associated with more severe ophthalmopathy (Kendler et al. 1993; Perros et al. 1993). The reason for these associations is unknown, but smoking behaviour might be involved. In a case-control study it was found that smoking greatly increased the risk for GO (odds ratio 7.7, 95% CI 4.3 to 13.7); patients with Graves' hyperthyroidism without eye changes were also more often smokers than control subjects (odds ratio 1.9, 95% CI 1.1 to 3.2). Among the patients with GO smokers had more severe eye disease than nonsmokers (Figure 2).


Figure 1:



Unusual presentation of Graves' ophthalmopathy as unilateral 'malignant' eye disease. The male sex, advanced age and heavy smoking all predisposed this patient to the development of severe eye disease; note the absence of exophthalmos in this case of dysthyroid optic neuropathy.


GO is usually but not invariably associated with Graves' hyperthyroidism. In our own series of 125 consecutive GO patients Graves' hyperthyroidism was present in 77%, hypothyroidism in 2%, and euthyroidism in 20% (Wiersinga et al. 1988). In the patients with euthyroid GO thyroid abnormalities (like a blunted TRH test, failure to suppress radioiodine thyroidal uptake with T3, thyroid autoantibodies) are found in 89%, and hyperthyroidism develops subsequently in 14% (Burch and Wartofsky 1993). As evident from pooled data of 842 patients with both GO and Graves' hyperthyroidism, the eye disease becomes manifest before hyperthyroidism in 19.6%, concurrent with hyperthyroidism in 39.4%, and after hyperthyroidism in 41.0% (Burch and Wartofsky 1993). It follows that autoimmune thyroid disease is present in the vast majority if not all GO patients. Conversely, it has been argued that the vast majority if not all patients with Graves' hyperthyroidism also have GO. This view is based on evidence for subclinical GO in Graves' hyperthyroidism without apparent eye disease, encompassing a shift to higher proptosis values in this group compared to healthy subjects, an abnormal increase in intraocular pressure on upgaze in 61%, and enlarged extra-ocular eye muscles on ultrasound or CT scan in 70-100%.