What role does genetics play in hypothyroidism?

July 21, 2006

A curious adult from Arizona asks:

"What role does genetics play in hypothyroidism or the effects of hypothyroidism?"

Many things can cause hypothyroidism, or low thyroid hormone. One of these things is genetics.

But it isn't a simple “one gene, one disease” sort of problem. Genetics can play many roles in causing this condition.

Before going into all of this, let's quickly go over what hypothyroidism is.

What is hypothyroidism?

The thyroid is a gland in your neck that makes thyroid hormone. This hormone travels in the blood and affects the body’s functions in different ways.

When your body doesn't make enough thyroid hormone, you can feel tired all the time. You may feel cold, gain weight, have dry skin or have a lump in your neck. The lump comes from the thyroid working extra hard to try to make enough thyroid hormone.

As I said, lots of things can cause hypothyroidism. Worldwide, the most common way to get hypothyroidism is to not get enough iodine. This isn't a problem here in the U.S. because most of our salt has iodine in it.

So why do people in the U.S. get hypothyroidism? The most common way is through genetics. There are at least three ways genes can be involved.

Thyroid model
The thyroid gland is located in the throat and produces thyroid hormone. When the thyroid doesn’t make enough thyroid hormone, it’s called hypothyroidism. (Image via Shutterstock)

Causes of hypothyroidism

Some babies are born with hypothyroidism. When you are born with it, it is called congenital hypothyroidism.

Congenital hypothyroidism can come from either a broken thyroid gland or by not making enough thyroid hormone. There are many, many DNA changes in lots of genes that can cause this problem.1

To make a thyroid gland, lots of genes need to work together. The same is true for making thyroid hormone. If something goes wrong with any of these genes, the gland won't work right, and you'll get congenital hypothyroidism.

It's kind of like building a car. These genes work together like factory workers on an assembly line -- each worker adds a piece until at the end, you have a car.

Imagine that halfway through the assembly line, someone doesn't put on the wheels. It won't matter if everyone else does everything right, the car still won't go.

The same thing is true with the genes to make a thyroid or thyroid hormone. If one gene doesn’t work, you don't make enough thyroid hormone and you end up with hypothyroidism.

Another way you might have hypothyroidism is if you don't have the right number of chromosomes. For example, women with Turner syndrome are missing an X chromosome and people with Down syndrome have an extra chromosome 21.

Both groups can have hypothyroidism as well.2,3 From this, we know that different genes on different chromosomes can cause the same problem.

Thyroid exam
There are many things that can cause hypothyroidism, including genetics, low iodine levels, and autoimmune dysfunction. (Image via Shutterstock)

Autoimmune hypothyroidism

A third way to have this problem is when the body attacks its own thyroid gland. Genes are still involved. This is called an autoimmune response.

Usually the body can tell what's its own, and what's foreign. This is what helps us fight infections. Our immune system attacks anything that is foreign to our body, like a bacteria or virus, but leaves our own cells alone.

People with autoimmune problems have a confused immune system. In these cases, the immune system recognizes some of itself as foreign and attacks. As you can imagine, this can cause all kinds of problems.

Multiple sclerosis and lupus are examples of autoimmune diseases. And so are some cases of adult hypothyroidism.

The immune system can sometimes think that the thyroid gland is an invader and attacks it. If the attack is a long one, the thyroid can't make thyroid hormone anymore.

But what has this got to do with genes? Well, genes are responsible for regulating our immune system. And problems with these genes can make these kinds of diseases more common.

These genes involved are found in an area called the Major Histocompatibility Complex or MHC. What scientists have found is that some of these genes have DNA changes in people with autoimmune hypothyroidism.4 These changes are thought to make it more likely that someone might develop the disease.

Autoimmune diseases can cause too much thyroid hormone to get made too. In Graves' disease, the body attacks itself and ends up making too much thyroid hormone, which is also a problem.

Other causes of hyperthyroidism

As you can see, genes are a major part of hypothyroidism. But it is important to note that genes are not enough to cause hypothyroidism.

Having some of the DNA changes we talked about increases the chances that something will trigger hypothyroidism, but does not guarantee it.

There are plenty of people with these changes who don't have hypothyroidism. And lots of people with hypothyroidism who do not have these changes.

So, like many complex diseases, it is a combination of genes and the environment that lead to hypothyroidism. In addition to discovering the genes involved, scientists are actively trying to find what in the environment triggers hypothyroidism.

Author: Dr. Devasena Gnanashanmugam

When this answer was published in 2006, Devasena was a postdoctoral fellow in the Department of Pediatric Infectious Diseases, studying the oral polio vaccine in Yvonne Maldonado's laboratory. Devasena wrote this answer while participating in the Stanford at The Tech program.

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