BACKGROUND
Graves’ disease is the most common cause of hyperthyroidism in the United States. Radioactive iodine therapy has been used for treatment of Graves’ disease since the 1940s. The thyroid is the only gland that takes up and stores iodine, which is used to make thyroid hormone. Radioactive iodine works by being taken up into the thyroid and destroying the gland. Initially, the goal was to find the right dose of radioactive iodine to bring the thyroid hormone levels back to normal, but this approach did not work well as the hyperthyroidism would often recur if the dose was too low. The current approach is to give a dose of radioactive iodine to completely destroy the thyroid gland, so most patients develop hypothyroidism within the first year of treatment.

One area of debate is when to start thyroid hormone treatment after radioactive iodine therapy. Past studies showed increased risk of Graves’ eye disease, weight gain and poor quality of life if patients develop hypothyroidism. To catch when the thyroid hormone levels fall into hypothyroid range patients need close monitoring. The American Thyroid Association recommends testing thyroid hormone (free T4 and total T3) and TSH levels for the first 2 months then to continue every 4 – 6 weeks for 6 months or until hypothyroidism develops and stable levels are reached with thyroid hormone treatment. There are 3 main management approaches during this period. Medications to decrease the thyroid hormone levels can be continued after radioactive iodine therapy treatment, or these medications can be used with thyroid hormone at the same time (block and replace), or the levels can be checked without any medication until hypothyroidism develops and then treatment with thyroid hormone is started. The main goal of this study was to find out how often and when the thyroid hormone abnormalities developed after radioactive iodine therapy and to compare the effects of different management strategies.

THE FULL ARTICLE TITLE
Perros P et al 2022 Post radioiodine Graves’ management: The PRAGMA study. Clin Endocrinol (Oxf ). Epub 2022 Mar 11. PMID: 35274331.

SUMMARY OF THE STUDY
The study was done in the United Kingdom. Patient information was found through reviewing databases of 31 National Health Service hospitals. Adult patients with confirmed Graves’ disease who were treated with radioactive iodine and had follow up information over 12 months following treatment were included. Medical records were reviewed to collect the thyroid test results and the results were grouped as hypothyroid, hyperthyroid, euthyroid, mild hypothyroid, or mild hyperthyroid then analyzed divided into 3-month quarters.

A total of 812 patients were included in the study. Hyperthyroidism was most common in the first 3-months after RAI (26%). Hypothyroidism was most common in the second quarter (60%). Overall, 80% experienced hypothyroidism at some point and 49% had hyperthyroidism. Only 5% of these patients did not have any abnormal thyroid tests. Differences between the 3 management groups were small, the only significant difference was less hyperthyroidism in the group treated with thyroid hormone only. No increase in the risk of worsening Graves’ eye disease, weight gain, or heart problems were found in the patients who had abnormal thyroid function. Only 21% of patients had the recommended tests at 6 weeks and 28% at 12 weeks, which increased to 80% by 12 months.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The authors concluded that patients often had abnormal thyroid hormone levels in the first 12 months after radioactive iodine therapy, especially in the first 6 months. The effectiveness of conventional management strategies to keep the thyroid function normal was low and there was no significant difference between them. Adherence to national guidelines about follow-up testing was also low, especially in the first 6 months when the abnormalities were more likely to happen.

The reported findings are important especially in showing the high risk of developing hypothyroidism in the first 6 months following radioactive iodine therapy and should raise awareness of both physicians and patients to follow the frequent testing schedule early on as suggested by national guidelines so thyroid hormone treatment can be started in a prompt manner. There is a need to develop better strategies after radioactive iodine therapy treatment to avoid abnormal thyroid function. The findings from this study can also guide physician-patient discussions prior to radioactive iodine therapy treatment of Graves’ disease.

— Ebru Sulanc, MD

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