Am I an HLA Mutant? Thyroid and Autoimmunity Genetics

Hello again, blog friends. We’re about 15 days out from Match Day and you know, it’s a little scary! But there’s nothing we can do now but wait. I’m passing the time by learning Japanese, applying to different types of jobs as back-up plans to grad school, and of course writing the blog.

Oh, and of course I’ve still been doing my volunteering at Crisis Text Line and in the NICU. I always look forward to my time in the NICU on Saturday nights. Holding babies releases oxytocin, so NICU nights always make me feel relaxed and peaceful. Well, except this past NICU night… because I was holding a baby that had just had abdominal surgery, and she threw up a whole tummy-full of orange bile-y throw up on me. So yeah so much for a relaxing night at NICU as we’re approaching Match Day lol.

This week I wanted to do another one of those “genetics of this complex-etiology medical condition” posts. But nothing to do with that NICU baby this time haha. Today, we’re going to talk about thyroid disease. It is extremely common for people to have issues with their thyroids, and I happened to be one of those humans.

My thyroid disease was called Graves’ Disease. I say was because I am now considered cured of it. I had my thyroid inactivated by radiation in August of 2017. I am now considered hypothyroid and I’m dependent on synthetic thyroid hormone.

My condition of hyperthyroidism is actually far less common than natural hypothyroidism, often related to a condition called Hashimoto’s Thyroiditis. Together, hypo and hyperthyroidism affect hundreds of millions of people. And yet, the causes of these conditions are largely unknown. They aren’t researched and funded the same way that cancer and heart disease are, because they just aren’t that fatal. And we thyroid folks are glad that thyroid issues are more of an inconvenience than a threat.

But like the craniofacial issues we discussed a few weeks ago, I think it’s important to look into the genetic and environmental causes of even these “lesser” issues. Genetic counseling is constantly growing and expanding into new subspecialties of medicine. At one of the programs I interviewed at, there are opportunities for genetic counseling students to sit in on primary care visits and contribute genetic knowledge as needed, so a broad awareness of health issues will be necessary. And of course, there’s always going to be patients wondering about random aspects of their health and family history. So today, let’s learn thyroid genetics.

Woman Touching Neck
A stock photo lady points out her thyroid

First of all, thank you stock photo woman, for pointing out where the thyroid is. Honestly, until I had issues with mine, I did not know. So yeah, the thyroid is a butterfly-shaped gland in your neck that produces thyroid hormones, called T3 and T4. The thyroid, like all body parts, is controlled by your brain. The brain sends out a hormone called Thyroid Stimulating Hormone (TSH) to call upon the thyroid to make T3 and T4. A person’s TSH levels can be determined by a blood test. Very high TSH levels indicate an underactive thyroid (the brain is begging the thyroid to make more of its hormone). A low TSH level (mine was 0, for example) means that there is little to no demand for thyroid hormone, which is an indication that it is already being overproduced.

T3 and T4 hormones essentially contribute to the speed of many body processes. High thyroid hormone means lots of energy, always feeling overheated, rapid heart rate, jitters, anxiety, insomnia, and a fast metabolism leading to constant hunger, weight loss, and digestive issues. Low thyroid hormone leads to tiredness, depression, weight gain, just a sluggish kind of body. Neither option is very healthy or comfortable.

Graves’ Disease (hyperthyroid) and Hashimoto Thyroiditis (hypothyroid) are the most common causes of thyroid imbalances. Both are autoimmune disorders. The genetics of autoimmunity are vvv complicated. But, let’s take a stab at learning the basics as they relate to thyroid conditions. Several autoimmune disorders, including these thyroid disorders, have been tied back to mutations in HLA region genes. The HLA region is a set of genes that give the body instructions on constructing an immune system. Autoimmune disorders occur when the immune system attacks itself in some way, so it makes sense that genetic causes have been elucidated in HLA genes.

Mutations in both HLA genes and thyroid structure/function genes have been linked to Graves’ Disease, though no specific mutation directly “causes” it. Meaning, even if we sequenced my genome and found a mutation in an HLA gene, we could not say that’s why I have Graves’ Disease. Genetic mutations are just one factor that contribute to the onset of the disease. Other factors include shifting hormone levels associated with puberty, infections, smoking, and probably a bunch of other things we haven’t realized yet.

And honestly, this is pretty crazy, the genetics and etiology of Hashimoto (the opposite condition) are basically the exact same! HLA group genetic mutations, infections, and hormones are some of the main causes of Hashi, as well as Graves’ Disease. These are also the same contributing factors for other autoimmune conditions like Type 1 Diabetes, Arthritis, and Celiac Disease. Why one person has some HLA group mutations and gets Hashimoto and another with HLA group mutations gets Celiac, we don’t completely know yet. Is a person with one of these conditions then at risk for others? Maybe! It may be too complicated and case-by-case to ever fully understand. But it’s interesting to appreciate how non-straightforward genetics can really be.

Thyroid disorders have such complex etiology, and luckily they are quite treatable, so there’s not a huge push for scientists to study them. The deadly thing gets the funding, and honestly that’s probably the way it should be!

It is important for future GCs to know what genetic research looks like for different kinds of diseases, just to be informed. In our careers, we’ll be the people patients come to when they have questions about their genes. As we study both well-understood genetic conditions, as well as explore genetic contributions to less-understood conditions, we will be ready to tackle any kind of DNA-related question that comes our way. Or, at least we’ll have experience researching so we can find out.

Happy Match Day soon! Hang in there, everybody.

-Laura Cooper-Hastings


NIH Genetics Home Reference for Graves’ Disease and Hashimoto

One Comment Add yours

  1. Lindsey Madsen says:

    This is awesome! I vote that your blog should be famous!


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