SOLUBLE INTERCELLULAR-ADHESION MOLECULE-1 (SICAM-1) CONCENTRATIONS INGRAVES-DISEASE PATIENTS FOLLOWED UP FOR DEVELOPMENT OF OPHTHALMOPATHY

It is commonly recognized that a few patients with Graves' disease (GD ) develop an overt ophthalmopathy, although most of them show subclini cal extraocular muscle enlargement by appropriate imaging techniques. At present, it is not possible to identify the subgroup of GD patients with subclinical retroorbital connective involvement. Recently, it ha s been shown that increase of soluble intercellular adhesion molecule- 1 (sICAM-1) serum levels is correlated to clinical activity score in a ctive Graves' ophthalmopathy (GO) patients with or without hyperthyroi dism, suggesting that sICAM-1 serum values could reflect the degree of ocular inflammatory activity. The aim of this longitudinal study was to evaluate sICAM-1 serum levels in GD patients without clinical ophth almopathy and to assess their possible relationship with occurrence of GO. We measured sICAM-1 serum levels in 103 initially hyperthyroid GD patients without clinical ophthalmopathy and in 100 healthy subjects. All patients were treated with methimazole for 2 yr. Sera were collec ted from all patients before treatment and then monthly for the first 6 months of therapy, every 2 months in the following 6 months, and fin ally at the end of the follow-up study. Patients developing GO were ex cluded from the follow-up at the onset of ophthalmopathy. During the f ollow-up 17 GD patients (16.5%, group 1) developed overt eye involveme nt (14 as active inflammatory ophthalmopathy and 3 as ophthalmopathy w ithout clinical retroorbital connective inflammation) and 86 (83.5%, g roup 2)did not. At start of the study, the mean of sICAM-1 serum conce ntrations did not differ significantly between the 2 groups, but it wa s significantly higher than in controls in both groups. No significant correlation between serum sICAM-1 concentrations and free thyroid hor mone levels was found in the 2 groups of patients. During the follow-u p study, a further increase of sICAM-1 serum levels was observed in 12 of the 14 patients (85.7%) of group 1 who developed active inflammato ry ophthalmopathy not only at the onset but also before clinical GO ap pearance. On the contrary, the 3 patients of group 1 that developed op hthalmopathy without clinical retroorbital inflammation did not show a ny further increase of sICAM-1 levels at every time of follow-up in co mparison with the starting values, even if their sICAM-1 levels were a lways higher than in normal controls. Finally, group 2 patients showed significantly decreased sICAM-1 levels throughout the follow-up perio d when compared with the starting values, although they were still sig nificantly higher than in controls. These results indicate that a furt her increase of sICAM-1 serum levels before the onset of clinical opht halmopathy may be a marker of subclinical retroorbital connective infl ammation in GD patients. Therefore, our study suggests that serial det erminations of sICAM-1 serum levels could help to identify and trace a t the right time those GD patients prone to developing active inflamma tory ophthalmopathy.