Randomized study of Graves’ disease treatments

Summary

This study looked at three common treatments for Graves’ disease (medication, surgery, and radioactive iodine) and their effect on the underlying cause of Graves’ (an autoimmune reaction).

This study was set up in one of the best ways to test the effects of different treatments – namely, a randomized study.  It was not a randomized controlled study, the ideal way to set up a study, because then you would have to give one group a sham (placebo) treatment.  That would be unethical in this case as not treating someone with Graves’ disease can have potentially fatal consequences.  The comparison, then, is among the three treatments, not the three treatments compared with no treatment.

A total of 179 patients with Graves’ disease were randomly assigned to one of three treatment groups – medication (methimazole and T4 hormone together), surgery (which removed almost, but not all of the thyroid gland), or radioioactive iodine (RAI) followed by T4 hormone.   The authors measured thyroid antibody (TRAb), levels in the patients before and after treatment.  High levels of TRAb are thought to be one underlying cause of  Graves’ disease.  The authors tested the hypothesis that treatment for Graves’ disease would reduce TRAb levels.

Because real humans (not lab rats) were being tested, some people dropped out for various reasons, some irrelevant (moved away), some relevant (one treatment didn’t work for them, so they switched treatments). For example, out of these 179 patients, 29 had normal starting TRAb levels (so couldn’t be used in this study to see if their TRAb levels normalized with treatment), one patient opted against the surgery, one opted out of RAI, one didn’t take the medication and ended up needing surgery, two couldn’t tolerate the medication, three surgical patients were still hyperthyroid afterwards and so also had RAI done.  These results are interesting because they show the variability in how people mentally and physically respond to these treatments.  However, because there were just a few patients in each group, they weren’t included in the bigger analysis.  That left only 131 people in the final analysis.

The results:  All three groups started out with high (~40) TRAb levels at the beginning of the study.  The medicated group (red line) and surgical group (blue line) both showed a decrease in TRAb levels over time and weren’t different from one another.  The RAI group (green line), however, showed a spike in TRAb immediately after treatment, and then declined slowly over time.  The RAI group never got as low as the other two groups, though.

TRAb is thought to be a trigger for Graves’ opthalmopathy, an eye disorder.  These findings may explain why RAI has been associated with an increased risk of Graves’ opthalmopathy, especially right after the RAI treatment.

Some caveats:  There weren’t that many people in this study.  They were all Swedish.  Those for whom the treatment didn’t work were excluded (ie – for 3 people surgery didn’t work and they got RAI (and so weren’t included), and for three others drugs didn’t work, so they got surgery.  There were ~30-40 people in each treatment group, and so the missing results of 3 “dropouts” might skew the results somewhat.

The authors emphasized the need for women who have had RAI treatment to get tested for TRAb if they later become pregnant.  The reason is that TRAb, if still high, can affect the baby.  Because RAI doesn’t reduce TRAb as much as the other treatments, this should be monitored carefully in pregnant women to avoid attacking the baby’s thyroid.

After stopping medication, TRAb rose in the medicated group.  This means that people have a choice of staying on the medication (with its side effects) or switching to a different, more permanent solution (surgery or RAI).  Patients and doctors need to weigh the pros and cons and risks of these various treatments.

The authors also discussed the large (29 out of 179) number of patients who had no abnormal TRAb.  They say that there are a number of tests that measure TRAb.  Some patients are positive on one, but negative on others.  However, all Graves’ disease patients will show up positive on at least one.  The Graves’ patients with normal TRAb levels in this study may have been positive on other tests, just not the one used by the authors.

Quick and dirty summary: thyroid antibodies decline after medication and surgical treatment of Graves’, but spike and then decline more slowly after radioactive iodine treatment.

Reference

Introduction: Autoimmunity against the TSH receptor is a key pathogenic element in Graves’ disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism. ObjectiveTo compare the effects of the common types of therapy for Graves’ hyperthyroidism on TSH-receptor autoimmunity. MethodsPatients with newly diagnosed Graves’ hyperthyroidism aged 20-55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients [≥]35 years of age). L-thyroxine (L-T4) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy. ResultsMedical therapy (n=48) and surgery (n=47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70-80% of the patients after 18 months. Radioiodine therapy (n=36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy. ConclusionThe majority of patients with Graves’ disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.

ResearchBlogging.orgLaurberg, P., Wallin, G., Tallstedt, L., Abraham-Nordling, M., Lundell, G., & Torring, O. (2008). TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study European Journal of Endocrinology, 158 (1), 69-75 DOI: 10.1530/EJE-07-0450


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