Etiology

• Sex

Since women are more susceptible to autoimmune diseases, there is a correlation that women are more likely to develop GD.

•  Age

GD shows the highest incidences in people aged between 20 and 40 years old. This means that people of this age group experience a higher risk while people outside of this range are not excluded from having the risk of developing this condition (News-Medical.net, 2012).

• Pregnancy

Though statistics show that hyperthyroidism occurs in less than 1% of pregnant women, pregnant mothers are more at risk of having an overactive thyroid than non-pregnant women. This is because thyroid hormones are needed for the development of a foetus's nervous system, and they rely on the mother's supply of these hormones (National Institute of Diabetes and Digestive and Kidney Diseases, n.d.). Moreover, postpartum periods also increase the risk of the onset of Graves’ disease (Wiersinga, 2016).

• Microbiota

Normally, symbiotic microbiota found in our gastrointestinal tracts benefits us by producing nutrients or enzymes that are necessary for our normal metabolism. However, when dysbiosis (imbalance of gut microbiota composition) occurs, it can alter the regulation of the immune system, causing various types of diseases, including autoimmune diseases like GD. The main gut flora changes that lead to GD are increased Prevotellaceae and Prevotella, Lactobacillus, as well as Veillonellaceae and Veillonella (Hou et al., 2021). 

These factors include lifestyle and dietary habits, as well as infections that may have caused damage to the thyroid.

• Stress 

There have been several case studies that demonstrate higher incidences of GD in the year following stressful life events. Be it emotional or physical stress, anxiety-causing events may act as a catalyst for the onset of GD in people with susceptibility genes (Mayo Clinic, 2020). 

• Drugs 

Some drugs can induce AITDs including GD. These drugs include Interferon-α, alemtuzumab, and anti-retroviral therapy medications (Wiersinga, 2016).

• Smoking 

It has been found that smoking can raise the risk of GD about two-fold and the effect is dose-dependent, meaning that the more one smokes, the more likely one is predisposed to developing this disease; vice versa, the risk decreases within years after smoking is stopped (Wiersinga, 2016).

• Selenium intake

Selenoprotein enzymes like glutathione reductase play a role in protecting our cells against oxidative damage caused by highly reactive species produced by our bodies like hydrogen peroxide. Since the thyroid gland consists of a high amount of selenium, evidence shows that low selenium levels are associated with poor immunity and hence, it is hypothesised that selenium deficiency may inflate the risk of thyroid immunity conditions such as GD (Wiersinga, 2016).

• Vitamin D

Low vitamin levels have been linked with multiple autoimmune diseases. Research also shows that GD patients were likely to possess vitamin D deficiency. For example, the levels of thyroid peroxidase antibodies (antibodies that attack the thyroid gland) in women decreased from those with vitamin D deficiency to those with vitamin D sufficiency (Wiersinga, 2016).

• Infection 

Some bacterial or viral infections can induce the development of GD. For example, research has identified a positive correlation between Y. enterocolitica infection and GD. This is due to molecular mimicry displayed by this bacteria.  One of its membrane proteins has been found to be involved in the production of thyroid-stimulating hormone (TSH) receptor antibodies, which also attack the thyroid gland, leading to GD (Wiersinga, 2016).