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TSH antibody levels predict Graves relapse after thionamides

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An underused test

The measurement of antibodies to the thyroid-stimulating hormone receptor is a useful clinical test that should be much more widely used in the United States. It’s a very accurate predictor of who’s going to get recurrent Grave’s disease after antithyroid drugs, but it’s misunderstood and not trusted.

Dr. Terry Davies

When the test was first introduced, many major thyroid experts didn’t accept it and didn’t believe it was useful based on research at the time. The difference with the current study is that it was done carefully.

Dr. Terry Davies is the director of the division of endocrinology, diabetes, and bone diseases at the Mount Sinai Beth Israel Medical Center in New York. He moderated the presentation and was not involved in the work.


AT ENDO 2016


BOSTON – Eighty-six percent of Graves disease patients with TSH receptor antibody levels of at least 2.0 mU/L at the end of thionamide therapy will relapse within 4 years, according to a British review.

TSH receptor antibody (TRAb) levels “are useful not only as a diagnostic tool but also as a prognostic tool. In patients where the risks of recurrent thyrotoxicosis are unacceptably high” – the elderly and those at risk for cardiovascular disease – “strong consideration should be given to primary radioiodine therapy” instead of thionamides, said investigator Nyo Nyo Tun of the Edinburgh Centre for Endocrinology and Diabetes.

Nyo Nyo Tun

Nyo Nyo Tun

Previous studies have suggested age and other risk factors for relapse after thionamides, but “have not [definitively] shown if elevation of TRAb levels” are predictive, she said at the annual meeting of the Endocrine Society.

Primary therapy with thionamides is more common in Europe than in the United States, where radioiodine tends to be the first choice. Part of the problem is that recurrence is known to be high after thionamides. The study suggests that using TRAb can help weed out patients who are likely to fail so that thionamides can be used with greater long-term success. Ms. Tun said the Edinburgh center routinely uses TRAb to guide Graves treatment; patients with high levels either stay on thionamide for prolonged periods or opt for radioiodine.

The investigators retrospectively studied 266 patients with a first presentation of Graves disease who completed a course of thionamide at two U.K. hospitals. In addition to TRAb levels at diagnosis and cessation of thionamide, they assessed age, sex, smoking status, free T4 levels, total T3, and time to normalization of thyroid function over 4 years of follow-up.

After thionamide cessation, thyrotoxicosis recurred in 31% of patients (82/266) at 1 year, 43% (111/261) at 2 years, 54% (125/232) at 3 years, and 66% (128/193) at 4 years.

Very high TRAb levels at diagnosis – those above 12 mU/L – were associated with a statistically significant 84% risk of recurrence over a 4-year period, compared with a 57% risk with diagnosis levels below 5mU/L (P = .002).

TRAb levels below 0.9 mU/L at cessation of an 18-month course of thionamide treatment were associated with a 22% risk of recurrence at 1 year and a 58% risk at 4 years. Those risks were significantly higher in patients whose TRAb levels were at least 2 mU/L at thionamide cessation, who had a 51% risk at 1 year and an 86% risk at 4 years (P less than 0.001). Relapse risk was highest in the first 18 months after cessation.

Younger age and time to TSH normalization also predicted relapse to some extent. Among patients who stayed in remission for 4 years, TSH normalized at a median of about 4 months after the start of drug treatment, but 6 months in those who relapsed. Similarly, patients who relapsed were a median of 39 years old at diagnosis; those who did not were a median of 47.

The investigators had no relevant financial disclosures.

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