Graves' disease: Is it better to start with lower-dose therapy?

If lower doses of drugs for Graves' disease are used at the start of treatment, adverse effects are less common too.

Graves' disease is a common cause of hyperthyroidism or 'overactive thyroid'. It affects about 2 out of every 1,000 men (0.2%) and 20 out of every 1,000 women (2%). This often leads to a visible enlargement of the thyroid gland. This swelling in the neck is called a goitre. The internal consequences of an over-function of the thyroid are more serious though. If the thyroid produces too much of particular types of hormones, it can cause an increase in the metabolic rate, rapid heart rate and nervousness.

Graves' hyperthyroidism is caused by a malfunction of the body's own immune system. It produces antibodies that allow the thyroid to grow and release too many hormones. The overproduction of hormones can be reduced with anti-thyroid medications. Using these drugs, though, is something of a balancing act. If the dose is too low, recurrences could be more common. If the dose is too high, adverse effects are a problem. Relatively common adverse effects include allergic skin reactions (rashes) and, rarely, a reduction in particular defensive cells of the immune system. This makes the person more vulnerable to infections.

In June 2009 the US regulatory authority FDA (the Food and Drug Administration) issued a safety alert about a particular anti-thyroid medication: propylthiouracil has been found to cause severe damage to the liver. If you are taking this medication, you can talk to your doctor about the benefits and possible harms of taking it and find out about the warning signs of liver damage.

Researchers are still looking for a way to find the best dose for each patient. The latest findings are described in a systematic analysis of the available trials, published by researchers from the Cochrane Collaboration, an international network of researchers. They analysed 26 trials involving nearly 3,400 participants who had treatment for at least six months and were followed up for at least a year. The analysis showed that two particular variations of treatments for Graves' hyperthyroidism have been tested the most in trials. One of the strategies was to start with a relatively high dose. The alternative involved starting off with a lower dose that was then increased over the following weeks.

The trials showed that there were fewer adverse effects if the dosage was slowly increased. Out of 100 people who used this treatment, 9 stopped taking the medication (9%). About 5 in 100 developed a skin rash (5%). In comparison: out of 100 people who started with the high dose, 16 stopped taking the medication (16%) and 10 out of 100 had a skin rash (10%).

There is still not enough evidence to know whether one of these two types of treatment result in more recurrences, though.


Author: German Institute for Quality and Efficiency in Health Care (IQWiG)

© IQWiG (Institute for Quality and Efficiency in Health Care)