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GRAVES’ EYE DISEASE
Effect of radioactive iodine therapy on thyroid eye disease

CTFP October 2021

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BACKGROUND
Radioactive iodine therapy has been used for many years to treat hyperthyroidism due to Graves’ disease, which is the most common cause of hyperthyroidism in the United States. It is currently the most common treatment for Graves’ disease in the United States. Radioactive iodine therapy works because the thyroid is the only organ that can take up and store iodine. Thus radioactive iodine is taken up by the overactive thyroid gland, stored and causes destruction of the gland to treat the hyperthyroidism.

Thyroid eye disease (TED) is a complex disease that causes inflammation of the eyes, eye muscles and the surrounding tissues. TED is most often seen in patients with Graves’ disease. Radioactive iodine therapy has been associated with worsening of TED, particularly in smokers. Because of this, there are different treatment strategies currently in use to dose radioactive iodine in Graves’ disease. Some methods use a fixed dose of radioactive iodine whereas others calculate a dose based on size of the gland and the activity as determined by a radioactive iodine uptake scan.

This study sought to determine if there were any differences in worsening of TED based on the radioactive iodine treatment strategy used. These investigators examined the effect of three different radioactive iodine dosing protocols on treatment of hyperthyroidism and thyroid eye symptoms due to Graves’ disease.

THE FULL ARTICLE TITLE
Ariamanesh S et al 2020 Effect of different 131I dose strategies for treatment of hyperthyroidism on Graves’ ophthalmopathy. Clin Nucl Med 45:514–518. PMID: 32433165.

SUMMARY OF THE STUDY
This study is clinical trial of three different radioactive iodine dosing protocols for the treatment of Graves’ disease. They recruited 92 patients (58 women and 34 men) with hyperthyroidism due to Graves’ disease with no or inactive thyroid eye symptoms at baseline.

The patients were randomized to one of three groups of RAI dosing: Fixed low dose – 7 mCi; Fixed high dose – 15 mCi and Calculated dose – 150 Ci per gram of thyroid tissue. All patients were assessed at baseline, 6 months, and 12 months after receiving a treatment dose of radioactive iodine. They measured thyroid function tests as well as performed measurements of eye disease activity, including degree of eye protrusion (proptosis) and a clinical activity score (CAS). Successful treatment response was defined as development of hypothyroidism, subclinical hypothyroidism, or normal thyroid function. Any patient with persistent hyperthyroidism or subclinical hyperthyroidism after radioactive iodine therapy was considered a non-responder.

At 12 months, the successful treatment of hyperthyroidism was higher in the Fixed High Dose (94.4%) and Calculated Dose (92.9%) groups compared to Fixed Low Dose group (66.7%). The treatment in the Calculated Dose group was as effective as the Fixed High Dose group despite administering lower overall radioactive iodine doses and thus exposing the patient to a lower amount of radioactivity. Eye exams were performed at baseline and 6 months. The patients in the Calculated Dose group had higher clinical activity scores at baseline. Radioactive iodine therapy was associated with a worsening of proptosis and CAS overall, however the CAS was more frequently increased in the Fixed High Dose group (34.4%) compared to the other groups (Fixed Low Dose 13.8%, Calculated Dose 6.4%).

In summary, this study demonstrated that Fixed High Dose and Calculated Dose effectively treat hyperthyroidism but that the Calculated Dose protocol was associated with fewer progressive thyroid eye symptoms.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The calculated dose protocol was able to successfully treat Graves’ hyperthyroidism with overall lower radioactive iodine doses and was less likely to be associated with progressive thyroid eye symptoms than the fixed high dose treatment. Both of these treatment protocols were much better than the fixed low dose protocol in treating the hyperthyroidism. Clinicians who use radioactive iodine to treat Graves’ hyperthyroidism may want to consider giving a calculated dose instead of a fixed high dose of radioactive iodine to minimize potential for worsening thyroid eye disease.

 

— Whitney W. Woodmansee MD

ABBREVIATIONS & DEFINITIONS

Radioactive iodine (RAI): this plays a valuable role in diagnosing and treating thyroid problems since it is taken up only by the thyroid gland. I-131 is the destructive form used to destroy thyroid tissue in the treatment of thyroid cancer and with an overactive thyroid. I-123 is the nondestructive form that does not damage the thyroid and is used in scans to take pictures of the thyroid (Thyroid Scan) or to take pictures of the whole body to look for thyroid cancer (Whole Body Scan).

Radioactive iodine uptake (RAIU): this is a measurement of activity of the thyroid gland and is reported as the percent of a dose of radioactive iodine that is retained in the thyroid gland 24 h after the dose is given. An increase in RAIU usually indicates hyperthyroidism.

Thyroid eye disease (TED): also known as Graves ophthalmopathy. TED is most often seen in patients with Graves’ disease but also can be seen with Hashimoto’s thyroiditis. TED includes inflammation of the eyes, eye muscles and the surrounding tissues. Symptoms include dry eyes, red eyes, bulging of the eyes and double vision.

CAS: Clinical Activity Score, a scoring system used to evaluate patients with Graves’ ophthalmopathy, and is based on classical signs of inflammation (pain, redness, swelling and function) and that helps predict which patients will benefit from immunosuppressive treatment

Proptosis: abnormal protrusion or displacement of an eye or other body part.