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Background  Ophthalmopathy is a common manifestation of Graves’ disease (GD) occurring in up to 50% of patients. Mild eye signs are also common in patients with Hashimoto’s thyroiditis. Whilst a genetic predisposition to GD has been demonstrated this is not the case for the ophthalmopathy which often runs a separate course.    Objective  We determined the prevalences of eye and eyelid signs and positive thyroid and orbital antibody tests in first and second degree relatives from a single family with multiple cases of Graves’ disease, ophthalmopathy and Hashimoto’s thyroiditis.    Design  The study cohort comprised 16 subjects from the same family, 4 probands namely, 3 with GD and one with Hashimoto’s thyroiditis and hypothyroidism and 12 of their euthyroid first or second degree relatives. We measured antibodies against calsequestrin (CASQ1) and collagen XIII in an enzyme-linked-immunosorbent assays and TSH-Receptor (TSH-R) antibodies as i) TSH-R binding inhibiting immunoglobulin (TBII) and ii) thyroid stimulating immunoglobulin (TSI). Eye signs were classified and quantified using the clinical activity score (CAS), NOSPECS classes, Nunery types 1 and 2 and the margin-reflex-distance (MRD) as a measure of upper eyelid retraction (UER).    Main outcomes  Whilst significant ophthalmopathy was uncommon in the relatives, mild eye signs, in particular UER, were demonstrated in about a third of them. The presence of eye signs was moderately, but not significantly, associated with the detection of CASQ1 and collagen XIII antibodies, but not TSH-R antibodies.    Conclusion  Our study demonstrates a significant prevalence of positive orbital antibody tests and ophthalmopathy in probands with thyroid autoimmunity and their euthyroid relatives, favouring a role of genetic factors in the development of ophthalmopathy in patients with thyroid autoimmunity.

Eye findings and immunological markers in probands and their euthyroid relatives from a single family with multiple cases of thyroid autoimmunity