Surgery, Statins Linked to Lower Graves' Complication Risk

Bridget M. Kuehn

December 15, 2014

Thyroidectomy or long-term statin use may reduce the risk for thyroid-associated ophthalmopathy (TAO) in patients with Graves' disease, according to results from a large, observational study. The study was published online December 11 in JAMA Ophthalmology.

Graves' disease is a thyroid condition that affects about 1% of US women. About half of these patients develop TAO as a complication. This adverse event can become debilitating, causing excessively dry eye, double vision, and in rare cases, permanent vision loss, according to Joshua D. Stein, MD, associate professor of ophthalmology and visual sciences, University of Michigan, Ann Arbor, and colleagues.

At this time, physicians prescribe lubricating drops, glasses with prisms, or surgery to correct double vision or remove extensive tissue build-up, Dr Stein told Medscape Medical News. Physicians may also use corticosteroids to suppress the immune response, said Robert A. Goldberg, MD, professor of ophthalmology and director of the Orbital Disease Center at the University of California, Los Angeles, David Geffen School of Medicine. Rituximab and other immune-suppressing biologics are also being studied, but so far, the data are limited, Dr Goldberg said. Orbital radiotherapy also has demonstrated some efficacy for patients with thyroid diseases, but preventive strategies have been lacking.

"There's really no known way to prevent patients with Graves' disease from developing TAO," said Dr Stein.

Smoking is a known risk factor for developing TAO. Dr Stein and colleagues set out to identify other potential risk or protective factors. To do so, the authors analyzed data from 8404 beneficiaries in a large US managed care network who received a confirmed diagnosis of Graves' disease between 2001 and 2009. They found that 740 of these patients (8.8%) developed TAO. Patients with Graves' disease who underwent surgical thyroidectomy had 74% reduction in their hazard of developing TAO compared with patients who did not undergo the surgery (adjusted hazard ratio, 0.26; 95% confidence interval, 0.12 - 0.51). Patients who used statins for 60 days or more had a 40% reduced hazard for developing TAO (adjusted hazard ratio, 0.60; 95% confidence interval, 0.37 - 0.93). The researchers did not find an association between TAO risk and the use of other cholesterol-lowering medications or cyclooxygenase 2 inhibitors.

"It's a very provocative paper," Dr Goldberg said.

He noted there is a very weak literature suggesting that thyroidectomy might be useful for preventing TAO, but the evidence on statins has been inconsistent.

"This is the first study to show such a strong signal for statins and thyroidectomy," Dr Goldberg said.

He added that he expects to see more studies like this one that use previously unavailable data to mine for insight. However, he noted, this type of study has some limitations. For example, he explained, there may be something else about patients taking statins that makes them less likely to develop TAO. Controlled studies will be necessary to rule out such confounders, he said, but he also noted that the findings provide a good rationale for conducting a controlled study.

Dr Stein said he and his colleagues hypothesize that the anti-inflammatory effects of statins might help reduce the risk for TAO because inflammation is believed to be a contributing factor in TAO. The findings on the effect of thyroid surgery on TAO are likely to add to an ongoing debate about whether thyroid treatment has an effect on TAO. Dr Stein said removing the thyroid may help to quickly control thyroid levels and may reduce the autoantigens that develop as Graves' disease progresses.

Dr Stein and colleagues plan to conduct a large, prospective study to confirm whether statins or thyroidectomy are safe and effective as a preventive strategy or as treatment for TAO.

"Before we start recommending patients with Graves' disease start taking statins or undergo thyroidectomy, we would like to conduct a large, prospective study to confirm the findings of our analysis," Dr Stein said. "Since statins and thyroidectomy are not without side effects, we would want to be sure that these interventions are safe and efficacious and that the benefits of them outweigh the risks before making recommendations to alter practice patterns."

The study was funded by the National Eye Institute K23 Mentored Clinician Scientist Award the Blue Cross Blue Shield of Michigan Foundation; Research to Prevent Blindness; and the Bell Charitable Foundation. The authors and Dr Goldberg have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online December 11, 2014. Abstract

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