Risk Factors for the Development of Ophthalmopathy in Patients with Hashimoto’s Thyroiditis

Background: Ophthalmopathy, or thyroid eye disease (TED), is more often associated with Graves’ hyperthyroidism than Hashimoto’s thyroiditis. In the latter disorder, the pathogenesis of the eye signs may be different and the influence of well-known risk factors for the development of eye signs in patients with Graves’ hyperthyroidism, such as smoking, age and gender, have not been studied in patients with Hashimoto’s thyroiditis. The aim of our study was to identify the risk factors which might influence the development of ophthalmopathy in patients with Hashimoto’s thyroiditis.

Methods: A retrospective cross sectional study included 105 patients with Hashimoto’s thyroiditis with and without ophthalmopathy and investigated 6 potential risk factors namely; age, gender, smoking, vitamin D deficiency, serum TSH and serum levels of antibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg). A binary logistic regression test was used to determine whether one or more of the factors were predictive for i) ophthalmopathy ii) upper eyelid retraction (UER), often the only sign in patients with Hashimoto’s thyroiditis iii) the type of ophthalmopathy (congestive ophthalmopathy, ocular myopathy or both) or iv) the activity of the eye disease assessed as Clinical Activity Score (CAS), in patients with Hashimoto’s thyroiditis.

Results: Our analyses showed a protective effect of ageing on the development of ophthalmopathy in patients with Hashimoto’s thyroiditis, the risk decreasing by 5.4% for each additional year and a detrimental effect of smoking, with a risk of ophthalmopathy 5.5 times greater in smokers. Increased serum TSH was not shown to be a risk factor for ophthalmopathy or its severity. High serum levels of TPO antibodies were found to be protective against the development of UER but not ophthalmopathy. None of the tested factors seemed to influence the risk of any ophthalmopathy subtype namely, congestive ophthalmopathy, ocular myopathy or mixed disease. However, gender has an effect on the activity of ophthalmopathy, men with Hashimoto’s thyroiditis related eye disease being 18 times more likely to develop active ophthalmopathy than women.

Conclusions: Because the risk of ophthalmopathy in patients with Hashimoto’s thyroiditis decreases with age, but is linked to smoking at all ages, patients with Hashimoto’s thyroiditis should be advised not to smoke as a preventive measure against development of ophthalmopathy, regardless of their age. Hashimoto’s thyroiditis-related ophthalmopathy is more active in male patients who should therefore be monitored more closely. The mechanism for the observed risk reduction of UER development in the presence of high levels of TPO antibodies could be studied to help with our understanding of the pathophysiology of ophthalmopathy and the development of new therapies.