Graves' disease is a serious condition caused by an overactive thyroid gland. Patients feel agitated, as if the body's thermostat is set too high: they feel warm, sometimes get hot flashes, feel very tired, are very hungry, but still lose weight despite eating a lot. Graves also has a great impact psychologically: some patients are forced to stop working.  

The impact of Graves on daily life 

'The symptoms with Graves are intense’, Van der Spek explains. 'This has not only physical, but also psychological consequences. You actually have too much thyroid hormone on board and that disrupts all kinds of processes in your body. Sometimes the symptoms are so intense that working is no longer possible.' The disease primarily affects women between the ages of 30 and 50, often for no apparent reason. 

Current treatments offer only symptom relief. The medication currently given inhibits thyroid activity. In severe cases, the thyroid gland is removed or destroyed with radioactive iodine. 'The problem is that these treatments do nothing about the underlying cause,' she stresses. 'In half the cases, the disease just comes back after medication.' 

Hypothesis: the gut microbiome as key 

The core of Van der Spek's research focuses on the hypothesis that the gut microbiome plays a role in the development of Graves' disease. She suspects that certain bacteria, viruses or other microbes in the gut are so similar to thyroid receptors that the immune system becomes confused and produces antibodies that make the thyroid overactive. 'We know that the gut microbiome is different in Graves patients than in healthy people,' Van der Spek explains. 'Whether those changes are the cause or the consequence of the disease is not clear.' 

The research will use new technologies and computer models to investigate whether the microbes in the gut of Graves patients are the underlying cause of the disease because they closely resemble the thyroid receptor. This may explain why the immune system makes this crucial mistake. 'This kind of model has been used successfully before in antiphospholipid syndrome and other autoimmune diseases, but not yet in Graves,' she explains enthusiastically. 

From symptom relief to cure 

With her research, Van der Spek hopes not only to better understand the cause of Graves, but also to discover new possibilities for treatments. 'If we know which bacteria play a role, we can focus on treatments that eliminate these bacteria or limit their influence. This would be a huge step, because we would then address the disease at its cause, rather than just treating symptoms.' 

In addition, the research could contribute to personalized treatments. 'We also hope to better predict who responds well to medication and who does not. That would mean we could treat patients in a more targeted way, saving a lot of suffering and costs.' 

The start of a promising project 

Van der Spek received the AUF Startstipendium for this research from the Amsterdam University Fund, which allows her to hire staff to support her research. 'I work as a doctor and don't have much time for research. Thanks to this grant, I can employ a research assistant and a PhD student to help me,' she explained. The project will start as soon as the medical ethics committee gives permission to include patients. 'I expect the first results by the end of 2025, during which we will hopefully have a clearer picture of the role of the gut microbiome in Graves.' 

A step into the future 

Although much is still unknown, Van der Spek's research offers hope for the future. 'Graves is often seen as a minor autoimmune disease, but it has a huge impact on patients' lives,' she says. 'I want to change that by contributing to better treatment - maybe even a cure.'