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BackTable / ENT / Article
What Causes Hashimoto’s Disease? Pathophysiology, Symptoms & Diagnosis
Julia Casazza • Updated Jul 10, 2024 • 38 hits
Hashimoto’s thyroiditis, the most common cause of hypothyroidism, results from an autoimmune attack on the thyroid. While the condition is associated with nutrient deficient and postpartum states, its exact pathophysiology remains unknown. In this article, we team up with thyroid expert and ENT Dr. Dana Gibbs to review the biological basis of this disease and labs for diagnosis and management.
This article features excerpts from the BackTable ENT Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.
The BackTable ENT Brief
• In Hashimoto’s thyroiditis, lymphocytes infiltrate and destroy the thyroid, damaging its function. When thyroid tissue regrows after an immune attack, the new tissue appears nodular.
• While Hashimoto’s is associated with inflammatory changes, the condition’s exact pathophysiology is unknown.
• Hashimoto’s thyroiditis can be diagnosed through serology (e.g. positive anti-thyroid peroxidase and/or anti-thyroglobulin antibodies) or biopsy showing lymphocytic infiltration.
• Weight gain is NOT present in many Hashimoto’s patients, though it can occur if the patient is hypothyroid.
• Normally, type II deiodinase converts T4 to T3. Under extreme stress, type III deiodinase converts T4 to metabolically inert rT3 to conserve energy. rT3 can interfere with T3 function by binding to its receptor.
Table of Contents
(1) The Pathophysiology of Hashimoto’s Thyroiditis
(2) Symptoms of Hashimoto’s Thyroiditis
(3) Working Up Suspected Hashimoto’s Thyroiditis
The Pathophysiology of Hashimoto’s Thyroiditis
Hashimoto’s thyroiditis is an autoimmune condition that destroys thyroid tissue and leads to hypothyroidism. Culprit antibodies are directed against thyroid peroxidase and thyroglobulin. In Hashimoto’s, lymphocytes trained against these antigens infiltrate the gland, destroying thyroid tissue and causing scarring. Constrained by scar tissue, new thyroid tissue regrows in a nodular pattern. While the exact pathogenesis remains unknown, potential triggers include iodine/selenium deficiency [1] and poor diet. The condition is more common following pregnancy, and female patients outnumber males five to one.
[Dr. Dana Gibbs]
Hashimoto's is autoimmune thyroiditis where the autoimmunity is directed at thyroid peroxidase and thyroglobulin, which are the support proteins and the manufacturing proteins of the thyroid hormone inside the thyroid gland. It's really common. If you do random sampling of US populations, the estimate is 15% of people have some evidence, either thyroid antibodies or lymphocytic infiltration of their thyroid on a biopsy, so it is super, super common. 15%, that's like, I don't know, 30, 45 million people. It's a lot of people in the US, and it's the most common cause of benign thyroid nodules.
The reason those thyroid nodules happen, when you get something back, when you get a biopsy back and it says it's an adenomatoid nodule, not a follicular adenoma, not a benign adenoma, what has happened is the inflammation happens, it destroys portions of the thyroid gland. Then it's a relapsing, remitting type of a condition. Scar tissue has a chance to form in the thyroid gland and then the follicles that now have to regrow to repair the damage are constrained by that scar tissue. They grow in this nodular pattern and some of them can get quite large, three, four centimeters and you're like, "Oh my gosh, that's thyroid cancer, we have to take that out."
People will come in and have these nodules removed, which leaves them then with even less thyroid tissue than they had before. It's something that ENT doctors see basically all the time and it slides right by because all they think about is, "Oh, I have to take out this thyroid nodule and then I'm going to send them back to the endocrinologist." I will tell you, 9 out of 10 endocrinologists that I have seen will go, "Oh, your TSH is normal, go away." The patient's like, "Yes, but I've gained 50 pounds, I feel like crap, my hair is all falling out." You sit there and you look at them and you can look through their hair to see the top of their scalp, their hair is so thin. It's like that list, I can't unsee those people…
[Dr. Ashley Agan]
Before we do that, before we move on about Hashimoto's, do we know what causes it? Are there certain risk factors? Is it more common in women versus men?
[Dr. Dana Gibbs]
Yes. It is an autoimmune disease. It is frequently the sentinel autoimmune disease and it's triggered by stress, it's triggered by a bad diet. It's triggered by high or low levels of certain minerals in your diet. Iodine and selenium were the two I was thinking of there. It's very, very common after pregnancy. It is five more times more common in women. It is very, very frequently unrecognized for years and years and years because we don't think to check for it. If your TSH is normal, then we don't think, "Oh, well, we need to do those thyroid antibodies and see what's going on."
The problem with the thyroid antibodies is it still misses about 10% of the people. If you feel their neck and they've got a thyroid nodule and you biopsy it and it has lymphocytes, whether or not they have antibodies, that's what it is.
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Symptoms of Hashimoto’s Thyroiditis
Symptoms of Hashimoto’s thyroiditis arise from impaired energy metabolism and inflammation throughout the body. Patients can report fatigue, cold hands/feet, infertility, constipation, thin hair, dry/itchy skin, hives, and vertigo. Weight gain can result, but it is neither sensitive nor specific for Hashimoto’s.
[Dr. Ashley Agan]
What is that list of symptoms? Do you screen for that? Obviously, now this is your main focus, but in the past when you were in practice, when you would see a patient with a thyroid nodule, would you screen for that list?
[Dr. Dana Gibbs]
Yes. I just added it to my systems review. The MAs filling that out, I just added it. "Okay, are your hands and feet cold? Is your body temperature low? Are you cold all the time? Do your hands ache?" My hands ached during residency and I just thought, "Oh, well, it's because I'm in the body and they're sticking out there and they're cold." I thought I had Raynaud's. That's how bad my hands were. Constipation is a big one, and for some people, really, really big. One of my fellow ENT colleagues that I didn't meet during training but I met afterwards, actually had the same issue and her main symptom was constipation.
To the point that she ended up having her colon removed because they couldn't figure out what was wrong with her. I was like, "Oh my goodness, that's so bad." She didn't figure it out until she became pregnant and her GYN gave her thyroid medicine and all of a sudden she was better. It's like, "What?" but it was too late. She'd already had the surgery. Hair, dry, itchy skin, sometimes hives. Vertigo, that's another thing ENT people see all the time. If you get a vertigo patient and it's not BPPV and you're like, "I don't know what to tell you," it can be that.
Weight gain isn't super common. People who come in who are obese are like, "Oh, this is my thyroid." I'm like, "No, maybe 10% of your weight gain is your thyroid, but the rest of it is other associated stuff." I was thin. Hell, we never had time to eat. I was thin, so nobody looked at me and goes, "You have thyroid," but you look at that list of symptoms, the low body temperature, the slow pulse, the brittle nails that break, the thin hair, all that stuff.
I would get to where I would walk into the room with a patient and look at them and they're puffy around their eyes because the autoimmune disease infiltrates glycosaminoglycans around your wrists, around your eyes, on your shins, that are similar to the way Graves disease does, but not so much the lid lag and all of that. I would get to where I could just walk in and go, "Oh, this is another hypothyroid patient." They would be, "Why are you here?" "Oh, it's sinus, it's this, it's that." I'm like, "Okay." We'd do their allergy tests, it'd come back not much and I'm like, "Let's check. Let's do my protocol to check your thyroid," which we'll get into in a minute.
Working Up Suspected Hashimoto’s Thyroiditis
Labs for Hashimoto’s thyroiditis assess autoimmunity, global energy metabolism, and related endocrine disturbances. The diagnosis of Hashimoto’s occurs through serology and imaging. Patients do not need to be symptomatic at presentation. Positive anti-thyroglobulin or anti-thyroid peroxidase (anti-TPO) antibodies are confirmatory for diagnosis. Similarly, a thyroid biopsy showing lymphocytic infiltration of thyroid tissue can confirm diagnosis.
TSH produced by the pituitary stimulates the thyroid to produce thyroid hormone in the form of inactive T4 and active T3. Type II deiodinase in the peripheral tissues converts T4 to T3. In times of increased stress (such as an autoimmune attack on the thyroid), type III deiodinase can convert T4 to reverse T3 (rT3). This nonfunctional metabolite binds to the T3 receptor to block T3 activity and tamp down energy metabolism. Checking free T4, total T3, and reverse T3 provides insight into energy homeostasis. The ratio of total to reverse T3 should be 12 in a healthy patient. TSH should be checked, but it can be normal or even low.
Since “not all fatigue is thyroid” and Hashimoto’s patients can present with other endocrine disturbances, patients benefit from an endocrine workup. Checking ACTH and morning cortisol assesses adrenal insufficiency; affected patients should be referred to endocrinology. Checking fasting glucose and fasting insulin facilitates HOMA-IR score calculation [2], which characterizes insulin resistance. If the patient in question is female and over age forty, testing sex hormones could identify another source of fatigue.
[Dr. Dana Gibbs]
In thyroid physiology, your body makes T4 and a little bit of T3, and then the T3 goes out into your body cells and T4 is converted to T3 in the target cells. Then the T3 goes to the nucleus, activates the protein cascades, and does all the things that thyroid hormone does to stimulate your metabolism. When you have high T4, it feeds back to the pituitary and the hypothalamus, and not only turns off the production of more T4, it causes a global blocking of the conversion of T4 to T3 throughout your body, which doesn't show if you don't check T3.
The other thing it does is that this high T4, it's a protection mechanism, so high T4 in the setting of Graves disease is a disaster, basically you just burn your whole body up. Your heart rate goes up, everything's terrible. Your body has fail-safe mechanisms to block that. One of them is this fact that it turns down the production of T3. The other one is a parallel pathway. T4 gets turned into T3 by something called type II deiodinase. There is also a type III deiodinase, and that type III deiodinase enzyme takes the T4 and turns it into reverse T3. Reverse T3 is an inactive metabolite, but not really, because it can still bind the receptor.
This is where me and the endocrinologist start to differ because they say reverse T3 is meaningless, it's an inactive metabolite. I'm like, yes, but it binds and blocks the receptor to T3. Even if you have enough T3, if you have enough of this blocker, then the relative function of your T3 is diminished because of that, so I check the reverse T3. Then I also check the total T3. The reason you have to compare reverse T3 to total T3 is because they are both protein-bound. It's the same proteins, and the reverse T3 is just a subset, but they're identical. You're getting an apples-to-apples comparison…
[Dr. Ashley Agan]
Back to our labs, so we said TSH, free T3, and reverse T3?
[Dr. Dana Gibbs]
Free T4, and then the total T3 to measure against the reverse T3. That's the ratio…
[Dr. Ashley Agan]
For the antibodies, you're checking anti-TPO and thyroglobulin?
[Dr. Dana Gibbs]
Anti-TPO and anti-thyroglobulin. Typically, if the story is right or if the patient has a palpable nodule, I will also check the antibodies for Graves disease, which is the thyroid receptor antibody, TRAb, or the TSI, thyroid stimulating immunoglobulin, just because sometimes you find an autonomously functioning nodule, sometimes you find Graves antibodies, and you do treat those people a little bit different. You can still treat them, but you have to be a little even more careful.
[Dr. Ashley Agan]
Any other labs that you like to look at?
[Dr. Dana Gibbs]
Because this comes along with stress so much of the time, I'm, typically, the first time I'm seeing a patient, going to check ACTH and cortisol, a morning cortisol, to make sure that they are not adrenal insufficient, because they go together. The other thing that really parallels this a lot is insulin resistance. I'm going to check uric acid, I'm going to check fasting insulin, fasting blood sugar, so that I can get a test called HOMA-IR. That's something I learned after ENT residency when I figured out none of these hormones exist in isolation and you can't treat one and then not pay attention to the other ones.
If it's a woman who's over 40, I'm going to check her sex hormones for sure as well, just because that's my practice. Now I wouldn't expect an ENT doctor to do that, of course. This problem rears its ugly head when people's estrogen starts to drop in perimenopause, so that's another thing that I will check.
Additional resources:
[1] Duntas LH. The Role of Iodine and Selenium in Autoimmune Thyroiditis. Horm Metab Res. 2015 Sep;47(10):721-6. doi: 10.1055/s-0035-1559631. Epub 2015 Sep 11. PMID: 26361258.
[2] Horáková D, Štěpánek L, Janout V, Janoutová J, Pastucha D, Kollárová H, Petráková A, Štěpánek L, Husár R, Martiník K. Optimal Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Cut-Offs: A Cross-Sectional Study in the Czech Population. Medicina (Kaunas). 2019 May 17;55(5):158. doi: 10.3390/medicina55050158. PMID: 31108989; PMCID: PMC6571793.
Podcast Contributors
Dr. Dana Gibbs
Dr. Dana Gibbs is an otolaryngologist specializing in thyroid, hormone, and metabolism conditions in Arlington, Texas.
Dr. Ashley Agan
Dr. Ashley Agan is an otolaryngologist in Dallas, TX.
Cite This Podcast
BackTable, LLC (Producer). (2024, May 28). Ep. 173 – Hypothyroidism Unmasked: The ENT’s Diagnostic Journey [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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