HOW HYPERTHYROIDISM HELPS COMBAT MALARIA… WAIT, WHAT?

 Hyperthyroidism is a common ailment, with over 200,000 cases in the United States annually. Also known as “overactive thyroid”, this condition occurs when an individual’s thyroid gland produces too much thyroid hormone, resulting in symptoms like weight loss, and a rapid/irregular heartbeat— the hormone is fundamental to regulating metabolism and energy use in the body, so overproduction of it drastically increases metabolism, thus leading to weight loss. That being said, hyperthyroidism is very rarely life-threatening, and several therapies exist to combat its daily effects. 

Malaria is a far different disease. 

A very rare ailment in the US, with fewer than 20,000 cases annually, malaria is caused by the plasmodium parasite. Despite its rarity in the US, the disease infects millions of people, globally, each year and is widespread in countries with poor sanitation and limited resources. Infected people usually present with a high fever and chills and, if left untreated, many die of severe complications due to internal bleeding. 

Within malaria subcategories, cerebral malaria (CM) is the most lethal and it typically affects children under five years of age. Cerebral malaria, as the name indicates, is identified via its role in promoting swelling of the brain, and leading to hemorrhaging (internal bleeding) as a result of the disruption of the blood-brain barrier. Symptoms of bleeding within the brain are severe, and late-stage symptoms of CM are seizures, paralysis, coma, and finally, death. This disease is devastating, easily transmitted via mosquitoes (which thrive in humid climates), and has dire consequences for those it infects. 

Cerebral Malaria can cause swelling and hemorrhaging in the brain.

Research is actively being done to mitigate the effects of malaria and several initiatives have been launched in the countries most vulnerable: mosquito netting and early detection are some of the more known steps that have been taken thus far. 

However, researchers have recently found a promising and puzzling connection between cerebral malaria and hypothyroidism that could lend itself to this humanitarian effort, though it is far from typical. Protection from cerebral malaria, the researchers from Spain find, can be achieved through hyperthyroidism. 

In healthy individuals, this loop is carefully regulated. In individuals with hyperthyroidism, the thyroid produces too much thyroid hormone which can lead to very high metabolism and weight loss.

Before understanding the nature of the relationship between hyperthyroidism and cerebral malaria, it is important to know what occurs when the body is fighting off an infection like malaria. Common knowledge of the immune system demonstrates the more obvious ability of the body to attempt and exterminate the pathogen causing sickness, in this case, the parasite plasmodium. What is less obvious is the function of other cells outside the immune system during this— many non-immune cells still actively try to limit the effects of the pathogen on the cells, and one way they accomplish this is through “metabolic reprogramming”. 

As mentioned before, hyperthyroidism is an overactivity of the thyroid gland and one of its symptoms is high metabolism (which results in weight loss). This can be summarized as being a function of the hormones the thyroid gland secretes—thyroid hormones are essential for metabolic function and its “reprogramming” under stress. 

When the body is infected, cells try to save energy, not expend it. This is due to the stress on the body during infection, where most of the energy goes to the immune system actively combatting the pathogen. As this occurs, other, less important, body functions are put on the back burner— thyroid hormones (TH) are measured to be excreted at lower levels during infection as the metabolism of the body slows to conserve energy. This is, after all, part of the body’s defense mechanism. But the question researchers posed was: Does this drop in TH have a similar effect if the individual has hyperthyroidism?

The image is above is taken from the research and it depicts the anatomical differences in size of the thyroid when a mouse either had or did not have hyperthyroidism or had or did not have cerebral malaria.

It turns out that there is a measurable effect of hyperthyroidism during cerebral malaria. Using mice, researchers were able to find out that mice with hyperthyroidism were less likely to develop severe symptoms like paralysis compared to mice without hyperthyroidism. With this lack of progression, hyperthyroidism in mice prolonged their life spans, meaning hyperthyroidism could increase survivability in individuals infected with cerebral malaria. Mice with hyperthyroidism also exhibited reduced brain swelling.

 Unfortunately, hyperthyroidism isn’t a cure-all for CM: disruptions to the blood-brain barrier still occurred despite the benefits otherwise noted, and several intermediate symptoms of malaria persisted. It is apparent though, that hyperthyroidism seems to limit the effect of malaria on the body in a significant way, significant enough to save lives. 

Further research needs to be done on the apparent benefits of hyperthyroidism for malaria-infected patients, but what is certain is that this research could usher in new and novel methods and theories to prevent this devastating disease from progressing and harming people.