Individual research recommendation details

Recommendation ID

NG145/3

Question

Are there subgroups of people with Graves' disease who have a particularly good response to antithyroid drugs?

Any explanatory notes
(if applicable)

Why the committee made the recommendations
The evidence suggested that radioactive iodine produced better long-term outcomes than antithyroid drugs in terms of thyroid status, but with a greater risk of thyroid eye disease. There was no convincing evidence of a difference between radioactive iodine and surgery. The economic evidence showed that radioactive iodine offered a better balance of benefits and costs than surgery (total thyroidectomy) and was more cost effective than antithyroid drugs. Although exposure to radiation will always lead to some small increase in relative risk of cancer, the evidence showed that this did not translate into an absolute effect that was clinically important. The committee agreed nonetheless that continued follow-up of people who have undergone radioactive iodine treatment was important and the 'as low as reasonably practicable' (ALARP) principle applied. They also agreed to make a research recommendation on the long-term effectiveness and safety of exposure to radioactive iodine.
The committee agreed, based on the clinical and economic evidence, that radioactive iodine should be offered as first-line definitive treatment for most people with hyperthyroidism secondary to Graves' disease. However they noted a number of important exceptions and specified these in the recommendations. The committee acknowledged that circulating levels of thyroid hormones are likely to rise following radioiodine administration and pre-treatment with anti-thyroid drugs would make radioactive iodine safer and lead to reduced symptoms of thyrotoxicosis. The committee also agreed that the response to antithyroid drugs is better in some people than in others. For adults who are likely to have a particularly good response to antithyroid drugs (mild uncomplicated Graves' disease), radioactive iodine and a course of antithyroid drugs could be equally appropriate options.
Some studies have suggested that some people are more likely to relapse after antithyroid drugs. These include males, younger people, people who smoke, people with a large goitre, people with high levels of thyroid hormones at the time of diagnosis and people with high levels of TRAbs. However, most of the studies were small and retrospective. The committee agreed that it would be very helpful to confirm these findings in large prospective multi-centre studies. They made a research recommendation to inform future guidance.
Calculated or fixed strategy for radioactive iodine
The evidence did not identify a clinically important difference between a calculated or fixed strategy in terms of radioactive iodine dosing. A calculated strategy has an increased cost because of the need for imaging (usually ultrasound) and uptake measurements. There are theoretical benefits from a calculated strategy to administer a more precise dose that could reduce potentially unnecessary additional radiation exposure, but the evidence did not indicate that this precision translated to clinically important benefits. The committee's experience is that, in the UK, radioactive iodine is usually given without calculating the absorbed dose. The committee agreed that there was too much uncertainty around the impact of the differing strategies to make a recommendation and chose to make a research recommendation.

Surgery options
The evidence suggested no clinically important difference between surgical options (total and hemithyroidectomy) for Graves' disease, but tended towards a benefit of total thyroidectomy in terms of relapse rates and harm in terms of increased risk of hypoparathyroidism. These findings were consistent with the committee's own experience. The committee agreed to recommend total thyroidectomy for adults with Graves' disease having surgery. This was based on their experience that people opting for surgery are generally seeking a definitive treatment.

How the recommendations might affect practice
The committee was aware that the recommendations would result in radioactive iodine being offered as first-line definitive treatment to more people than currently. This is likely to be cost effective as shown by the economic evidence.
Full details of the evidence and the committee's discussion are in evidence reviews: I, J, K, L: managing thyrotoxicosis.

Source guidance details

Comes from guidance

Thyroid disease: assessment and management

Number

NG145

Date issued

November 2019

Other details