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Graves + Hashimoto’s combo
Hashimoto’s + Graves disease is found in a person with
- at least one flare-up of TSH-Receptor stimulating antibodies (TSAb) causing a significant rise in T4 hormone and fall in TSH, often confirmed by a positive TSI or TRAb test.
- and at least one phase of hypothyroidism that was not caused by thyroid gland ablation, thyroidectomy, or Graves’ disease overmedication.
- may also develop signs of thyroid gland fibrosis and/or atrophy from TPOab and TBAb flares
Some people locate these patients as a subcategory of Graves’ disease, as McLachlan & Rapoport do (below), but a patient may begin hypo or begin hyper before manifesting the opposite syndrome or flip-flopping. Therefore, I locate them on the boundary.
McLachlan & Rapoport explain:
- “In Graves’ disease, the spontaneous change from hyperthyroidism to hypothyroidism (without ablative intervention with radioactive iodine or overtreatment with anti-thyroid drugs) may occur in two ways:
- “by the unexpected development of TBAb;”
- “or because the process of thyroid damage reflected in chronic lymphocytic thyroiditis overcomes the stimulatory effects of TSAb and, eventually, TSH”
In other words, as a Hashimoto’s patient, you can have a major flare-up of Graves’ antibodies during thyroid therapy. But the TSAb antibodies may never elevate your thyroid hormones above reference range because you have been on the Hashimoto’s or TBAb side of the map for a long time, and now your thyroid gland is now mostly fibrosed and/or atrophied.
A person can have even have Hashimoto’s with Graves Eye Disease, caused by Graves’ TSAb antibodies, without being hyperthyroid. Only about 50% (or fewer) of Graves’ patients will have Graves’ Eye Disease.
Hello, I’m an Atrophic Thyroiditis patient.
Hi, I’m Tania Smith, the main researcher and writer on Thyroid Patients Canada. I’m an Atrophic Thyroiditis patient, confirmed by ultrasound measurements.
My extreme ultrasound data (total gland volume 0.5 mL) when compared with the range of volumes found in AITD is more than enough evidence to put me in this corner of the antibody map.
I also have the classic confirming signs of an extremely high TSH at diagnosis (over 150 mU/L) that did not present along with any signs of goiter.
I think I probably flip-flopped between TSAb and TBAb dominance over three decades, based on my faint memory of symptoms and signs. However, I was never excessively hyperthyroid to cause the usual cardiovascular or other manifestations, and I never had the Graves’ Eye Disease found in a fraction of Graves’ patients.
Finally, sometime in my late 20s and early 30s, over a period of less than 5 years, I became severely hypothyroid. I can’t place when exactly, because I was also battling another autoimmune disease, Ankylosing Spondylitis, and I spent months on prednisone steroid therapy because it was the only medication they had back then that was effective.
At some point, the TBAb antibody rose to dominance, somehow combined with other antibodies and cytokines, and shrivelled my thyroid to the size of two crushed raisins.
Sometimes I tell people “it’s the size of one-tenth of a teaspoon.”
I also like to call my thyroid a “fibrosed flap of flesh.”
I can’t flip-flop anymore between hyper and hypo, I can only flop!
I’m now hypo for life.
Interestingly, at the microbiology laboratory, it now looks like I’m a poor fit for even a classic Hashimoto’s patient.
- My TG antibodies are always elevated (over 4 tests), and that’s the antibody that is supposed to be less frequent in Hashimoto’s.
- My TPO antibodies are there, but they’re never elevated (over 4 tests), and that’s the antibody that mainly defines Hashimoto’s.
What happened to my distinctive “Graves’ Hypo” antibodies? My TBAb and TSAb could have disappeared, as research shows they often do in Graves’ hyper as well. Alternatively, Alberta’s TRAb assay technology is incapable of showing my TBAb, since I have tested negative on a TRAb assay (twice).
Not all TRAb assays are alike. TBII tests reliably detect the blocking antibody, but good luck finding a TBII test–they’re being phased out and replaced by TRAb tests of varying sensitivities that don’t do what their manufacturers claim to do (Lytton, Schluter & Banga, 2018).
How much hormone can my gland produce? almost nothing.
I have proof. As a person on synthetic T3-only therapy (for reasons I’ll explain elsewhere), I was unknowingly underdosed for a period of 6 months, and my TSH rose to 15.0 mU/L while my FT3 was at 4.4 pmol/L about 30% of reference range. But despite that high amount of TSH stimulation, my thyroid only contributed 0.5 pmol/L of Free T4. I’ve also been told that this result of 0.5 pmol/L is below the range of accurate detection by most FT4 assays, so it’s possible my thyroid contributed zero FT4.
How TBAb causes suffering
According to my lab history, I suffered a flare of TBAb antibodies that kept my Free T3 levels continually below reference during my final three years of Synthroid therapy, despite high-normal Free T4. I experienced bouts of severe hypothyroidism.
The TBAb antibody that causes Atrophic Thyroiditis can cause poor T4-T3 conversion. This is because the DIO2 enzyme that converts a large amount of our daily T3 supply is normally upregulated by TSH (Park et al, 2018).
TSH receptors are located throughout the body, not just in the thyroid gland. TSH signaling throughout the body can be blocked by high levels of this antibody blocking TSH receptors. Wherever TSH receptors play a role in upregulating DIO2, that’s where the normal function of DIO2 can be blocked.
As a result, this antibody can cause the TSH to rise above reference range illogically in relationship to a high-normal Free T4, when it is maintained by thyroid therapy rather than thyroid secretion. As the antibody fluctuates, the TSH and T3 can fluctuate illogically.
Everything becomes illogical, the patient suffers, and the doctor may be tempted to blame the patient for not taking their medication correctly.
I finally ended up in Emergency three times in the final three months with daily unexplained chest pain attacks at random times times day and night. I switched to a T3-inclusive therapy which resolved my hypothyroidism.
Here’s how it feels to know my “autoimmune thyroid” identity.
First of all, I find the ignorance about my disease saddening and frustrating. My unique autoimmune etiology is related to many aspects of my health, which I’ll explain in future posts.
I can’t blame my doctors for not diagnosing me earlier, but I blame the system for making “experts” so incredibly ignorant of something that isn’t exactly hidden in the scientific literature.
- My bibliography on this condition currently contains 121 scientific articles that either focus on it or mention it.
It feels odd to know more about my type of thyroid disease than almost all doctors do nowadays.
My disease is firmly written into thyroid science history, but it’s been mostly forgotten. My region of the spectrum was falsely scribbled over with the word “Hashimoto’s” just because it is a place where hypothyroidism exists. It’s like a secret takeover happened. My territory was annexed.
Sometimes I feel lonely and weird, yet I know I’m not alone. Most of my AT buddies just haven’t been properly diagnosed yet because a dark age has clouded the eyes of most clinicians.
I prefer not to feel isolated off in the corner of autoimmune thyroid disease as part of a minority.
I’d rather be aware that I share antibody genes with so many of my thyroid buddies. I’m connected to the group.
I can identify with both Graves’ Disease patients and Hashimoto’s Thyroiditis patients because I’ve had your antibodies too. But I know I’m a rare bird now. I’m now something very few of you will ever become.
I can even say my gland status is similar to a patient with a full thyroidectomy, because I’m truly “thyroidless,” I’ve just never had thyroid surgery. Some people after a thyroidectomy have some small fragments of thyroid tissue left too.
Arise, ye cohort of raisin-thyroid people, and reclaim your autoimmune territory on the spectrum! If you’re one of us, I’d like to hear from you.
When seeing autoimmune thyroid disease, we don’t need a hierarchy.
When Davies and colleagues, and later, Larsen and colleagues, tried to create a classification of autoimmune thyroid disease, they created a rather confusing mess.
They started with mere words, the labels “Hashimoto’s” and “Graves.”
As you can see in Davies / Larsen’s categorization, after using “Hashimoto’s” and “Graves” as their upper layer of structure,
- They decided to divide Hashimoto’s into two, type 1 “euthyroid” and type 2 “hypothyroid.”
- Then they subdivided it by gland health: goiter or no goiter, 1a, b, 2 a, b.
- With Graves, they took an entirely different approach. They permitted Graves to have all three biochemical statuses (hyper, euthyroid, hypo), and they made those into 3a, 3b, 3c.
- They admitted that a person can be “euthyroid” Graves with a suppressed TSH, but they didn’t explain this apparent contradiction.
- For some reason, instead of putting “Atrophic thyroiditis” within the “hypothyroid Graves” sector, they shoe-horned it into a subtype of Hashimoto’s, even though it’s clearly associated with Graves’ TSH-receptor antibodies.
- They created a lot of repetition by mentioning that TPO and TG antibodies are found everywhere. TSH-receptor antibodies are mentioned in two separate places.
Anyone who knows the literature will ask logical questions like this:
- Why do you start with euthyroid status as #1? Why are you saying a euthyroid person has “Hashimoto’s thyroiditis” just because they have antibodies? That’s not a disease.
- Graves disease often presents with goiter, so why isn’t that important? Why is a goiter only important when classifying hypothyroidism?
- If goiter is so significant, why not talk bring up the fact that iodine deficiency can be a trigger of autoimmune thyroid disease as well as goiter?
- Why do you have no category for a person who transitions between Hashimoto’s and Graves?
- Why not mention Graves’ eye disease in all three categories of Graves, since that’s where it’s found?”
Obviously this classification scheme didn’t stick. Nobody says “You have Type 2B Hashimoto’s” or “I have type 3c Graves.” Why? Its categories didn’t have a physiological logic, and it didn’t make sense with the clinical reality.
Apparently, we threw up our hands in exasperation.
So now that we see everything through the TSH lens, we have collapsed all distinctions and overlaps, and now just see two diseases.
We now have two big blurry biochemical blobs:
- anything that goes “hypo” in one basket called “Hashimotos” and
- anything “hyper” is in the other basket called “Graves.”
Now this blinds us to etiology, gland health, and tissue euthyroidism.
Instead, we need a telescope and a map.
As I’ve outlined in a previous post, it’s clearer if we start with autoimmunity, the cause/etiology, and we take the approach of “mapping” autoimmune thyroid disease.
If we want to “see” a disease, we need a telescope with at least four lenses:
It’s not accurate to merge these spheres.
It’s ultimately not helpful to force naturally complex things to be simpler than they are in reality.
As we all know, our medical system often focuses on thyroid biochemistry. It’s the dominant lens they see everything else through. “Evidence-based medicine” has tended to focus on one type of “evidence,” hormone test results, when defining thyroid status. Much less emphasis is placed on thyroid ultrasound or other gland tests, antibody tests, and our symptoms or signs of “tissue euthyroidism.”
Antibody status is one thing. Gland health is another thing. Biochemical status “hypothyroid” is yet another thing. The cause-effect connections tend to go in one direction, but the connections between them are not inevitable. They are complex.
Each way of seeing thyroid status is like a different type of lens in a four-lens telescope, or if you like, each person’s thyroid disease may even be like a kaleidoscope.
Each lens has its own characteristics. Each aspect of thyroid status can affect and overlap with another in different ways under different conditions.
When you combine all four lenses in a single telescope, you can really see what is going on.
When we’re talking about “thyroid autoimmunity,” we’re mostly talking about an aspect of etiology, the ultimate cause(s) of our thyroid disease.
Etiology is complex enough on its own. We all have an “adaptive” immune system that forms antibodies. The triggers of thyroid autoimmunity are barely understood, and I won’t get into those here. (I do have hope, however, that in the “virus era” we’ve entered with COVID-19, more people will pay closer attention to the innate and adaptive immune system, and thus thyroid autoimmunity.)
What we do know for sure is that in autoimmune thyroid disease, special antibodies form that can attack various tissue types in our thyroid gland (and some anti-thyroid antibodies directly affect other bodily tissues as well, as science is learning).
Etiology is an important foundation that shapes our biochemistry, but etiology does not overdetermine our thyroid biochemical status. Once you have an antibody floating around in your blood, its effects are not always instant or inevitable.
Etiology has to go through not only thyroid “gland health” but also pituitary and hypothalamus “gland health” to get to our thyroid biochemistry.
Therefore, whether we manifest as biochemically euthyroid, hypothyroid, or hyperthyroid (the state we’d be in without any treatment) depends to some degree on which unique collection of antibodies we have and which antibody dominates over time to alter our gland status and function.
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Lytton, S. D., Schluter, A., & Banga, P. J. (2018). Functional diagnostics for thyrotropin hormone receptor autoantibodies: Bioassays prevail over binding assays. Frontiers in Bioscience (Landmark Edition), 23, 2028–2043. https://www.ncbi.nlm.nih.gov/pubmed/29772543
McLachlan, S. M., & Rapoport, B. (2013). Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa. Thyroid, 23(1), 14–24. https://doi.org/10.1089/thy.2012.0374
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Park, Eunkuk, Jaehoon Jung, Osamu Araki, Katsuhiko Tsunekawa, So Young Park, Jeonghyun Kim, Masami Murakami, Seon-Yong Jeong, and Sihoon Lee. 2018. “Concurrent TSHR Mutations and DIO2 T92A Polymorphism Result in Abnormal Thyroid Hormone Metabolism.” Scientific Reports 8 (July). https://doi.org/10.1038/s41598-018-28480-0.
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