Ask a Geneticist

by Dr. Devasena Gnanashanmugam, Stanford University

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

-A curious adult from Arizona

July 21, 2006

Many things can cause hypothyroidism, or low thyroid hormone. And, one of these 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.

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

Iodized salt reduces cases of
hypothyroidism.
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 this problem. 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 our salt has iodine.

So where 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.

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.

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.

Making the thyroid gland is like making
cars, lots of pieces need to work together
to have a car or a thyroid work.
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 halfway through that someone doesn't put on the wheels. Then it won't matter if everyone else does everything right, the car still won't go.

Same with the genes to make a thyroid. Or thyroid hormone. If the wheels don't go on, 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's syndrome are missing an X chromosome. And people with Down syndrome have an extra chromosome 21.

Both groups can have hypothyroidism as well. From this we can tell that different genes on different chromosomes can cause this problem.

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 new that is invading 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 autoimmune diseases. And so are some cases of adult hypothyroidism.

What happens is the immune system thinks the thyroid gland is an invader and attacks. If the attack is a long one, the thyroid can't make thyroid hormone anymore.

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

The fact that the Japanese also have higher rates of autoimmune hypothyroidism hints that genetics is involved. Even people of Japanese descent who live in different countries have higher rates of hypothyroidism. This is a telltale sign that genes are involved.

The genes involved are found all together in an area called the Major Histocompatability Complex or MHC. What scientists have found is that some of these genes have DNA changes in people with autoimmune hypothyroidism. 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.

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

Having some of the DNA changes we talked about increase the chances that something will trigger hypothyroidism. But they aren't destiny.

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.

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