Long Term Medical Treatment of Graves Disease

Graves disease is a fairly common disorder where the thyroid is stimulated by the immune system to produce high levels of thyroid hormone characteristically in response to anti thyroid stimulating hormone receptor antibodies (Anti TSHr abs). Thionamide therapies like propylthiouracil (PTU) or carbimazole are effective in blocking the manufacture and release of formed thyroid hormone into the blood stream but really don't do anything to affect the underlying pathological process causing Graves disease. In most cases we are waiting for the immune system to lose interest in producing these stimulating antibodies which can happen quite quickly over time, or it may take a lot longer.

Guidelines have acknowledged that as a result of the persistence of these stimulating antibodies, relapse rates can be high after thionamide therapy has been stopped. If the antibodies are still high after 12-18 months of blocking therapy, or if hyperthyroidism occurs, definitive therapies such as radioiodine ablation and surgical removal of the thyroid are recommended leaving the patient hypothyroid and dependant on thyroid replacement therapy.

An interesting observational retrospective study including 549 patients (mean age 36-41 years old) followed up to 36 years has identified some helpful and interesting trends.

  • In 50% of patients, TSHr abs became normal after 2 years of continuous therapy

  • Of the 50% that didn't normalise, another 20% normalised over the next 3 years of continued therapy

  • Over that time, half of the first group who normalised their TSHr abs ended up with high TSHr abs levels and were put back on thionamide therapy

  • At the end of follow up 37% had achieved remission on long term treatment from this group of relapsersIf antibodies normalised and stayed normal (25% of the total group), the chance of remission at the end of follow up was about 90%

  • Those that had persistently positive antibodies on treatment had a 20% chance of remission if they continued thionamide treatment for more than 5 years

Thionamide therapy is relatively safe and it seems that even in the long term, adverse effects such as liver dysfunction, joint problems, rash, and bone marrow failure are very rare. This study encourages those who wish to avoid radiation or long term hypothyroidism following definitive treatment options and who wish to stay on long term thionamide therapy with the understanding that success rates are lower.

The review article can be found in Clinical Thyroidology (June 2019) Vol 31(6):pp230-33 [link]