Let’s get to know what many of us thyroid patients have in common, and what makes each of us unique.
Are you an autoimmune thyroid disease (AITD) patient?
If so, what kind of autoimmune thyroid disease do you have?
How do you know for sure?
I ask this final question because very few of us know our complete set of thyroid antibodies.
Most of us are taught to think that “Hashimoto’s” and “Graves” are two mutually exclusive diseases, but they’re not that simple and pure.
There’s more than two types of autoimmune thyroid disease.
I’m an Atrophic Thryoiditis (AT) patient, which is kind of like Hashi’s because it causes hypothyroidism, but some of its features are really not like Hashi’s at all. I’ll talk about my own experience with AT at the end of this post.
Most of our doctors are trained to focus on diagnosing and normalizing our biochemistry. They put out fires and resolve current crises. They are not trained to understand the complexity of autoimmune etiology and its variable manifestations over time–over our lifetime.
The common mantra doctors are told, and are told to pass on to us, is that “your antibody status won’t make a difference to your treatment.”
Oh yes, it can, over time.
A too narrow autoimmune thyroid “diagnosis” can result in blindness to “prognosis” — the forecast of how a person’s disease could develop over their lifetime.
Undiagnosed aspects of autoimmune thyroid disease can manifest in unexpected ways or shift even while our thyroid biochemistry is being well managed.
Lack of knowledge and discernment can make us attribute our puzzling symptoms to other diseases. Many of us have symptoms that don’t seem to fit the stereotypical manifestations of the kind of thyroid disease we have been “pigeonholed” into.
Doctors, and even patients, can be tempted to blame stress, diet, lifestyle choices, or think we’re imagining things when we can’t figure it out.
Knowing the full spectrum can open our minds and help us connect the dots between our thyroid status and our overall health.
If our doctors can’t connect the dots in a brief appointment focused on one ailment alone, it’s up to us as patients to connect the dots by learning on our own (as our “brain fog” symptoms and time permit).
I’ll show you how to connect some of the dots, and how to see us as all connected.
3 basic types of AITD
Autoimmune thyroid diseases (AITD) consist of three major forms, each of which has a set of synonyms found in scientific research:
- Hashimoto’s thyroiditis (a.k.a. chronic lymphocytic thyroiditis,[CLT] “goitrous” autoimmune thyroiditis.)
- Graves’ Disease (a.k.a. Basedow’s disease)
- Atrophic Thyroiditis (a.k.a “primary myxedema,” “non-goitrous” myxedema, Ord’s disease, or even “primary hypothyroidism” when distinguished from Hashimoto’s or CLT)
I’ve arranged them in order of prevalence.
According to research, most AITD patients have Hashimoto’s, fewer have Graves’, and the minority have Atrophic Thyroiditis.
#3, Atrophic Thyroiditis, usually remains undiagnosed and is mistakenly lumped in with Hashiomoto’s by people who prefer simple dualism rather than the complex reality of the triad.
The most interesting fact revealed in decades of scientific publications is that all three of these subtypes of AITD share antibodies and can overlap and shift on a single “spectrum.”
“Hypothyroidism” is not exactly synonymous with “Hashimoto’s,” and it can resolve a lot of confusion if we understand why.
Even though a person can’t manifest as “hyperthryoid” and “hypothyroid” at the same time, under the surface, Graves’ and Hashimoto’s are not mutually exclusive diseases. These diseases often share antibodies, and they can manifest as more than one biochemical status over time.
The “spectrum” of AITD in research
The idea that autoimmune thyroid disease (AITD) is a “spectrum” is not new. It’s written all over thyroid scientific publications.
Here’s a sampling of quotations from scientific journal articles from 1965 to 2019 that show two or three, or more, types of AITD sharing a single spectrum.
I’ve chosen quotes that use some of the synonyms for Hashimoto’s and Atrophic Thyroiditis that I introduced above:
- “AITD affects many people worldwide and encompasses a spectrum of conditions ranging from Hashimoto’s hypothyroidism (HH) to Graves’ hyperthyroidism (GH)” (Effraimidis, 2019)
- “The spectrum of autoimmune thyroid diseases includes: Graves’ disease (GD), Hashimoto’s thyroiditis (HT), atrophic autoimmune thyroiditis, postpartum thyroiditis, painless thyroiditis unrelated to pregnancy and thyroid-associated ophthalmopathy. This spectrum present contrasts in terms of thyroid function, disease duration and spread to other anatomic location.” (Hajd-Kacem et al, 2009)
- “It has been suggested that Hashimoto’s thyroiditis, primary myxedema or AT [atrophic thyroiditis], and Graves’ disease are different expressions of a basically similar autoimmune process, and that the clinical appearance reflects the spectrum of the immune response in the particular patient.” (Jara, Vera-Lastra & Medina, 2008)
- “Autoimmune thyroid diseases are the more prevalent organ-specific autoimmune disorders in humans. They encompass a wide spectrum of clinical presentations, with hyperthyroid Graves’ disease at one end and atrophic myxedema at the other. Whether Graves’ disease and lymphocytic thyroiditis represent different aspects of the same disease or different diseases remains unclear.” (Orgiazzi, 2000)
- “Graves’ disease has recently been shown to exist in a euthyroid form in untreated patients. Sporadic reports of a hypothyroid form are beginning to emerge, thus illustrating the multifaceted nature of this disorder, with thyrotoxicosis at one end of the spectrum and hypothyroidism at the other. … It is suggested that, until more is known about this intriguing aspect of the Graves’ disease spectrum, the label ‘hypothyroid Graves’ disease‘ is justifiable.” (Christy & Morse, 1977)
- Title of article: “Primary Hypothyroidism and Hashimoto’s Thyroiditis: A Continuous Spectrum.” (Buchanan & Harden, 1965)
These quotations also show you how much even the scientists struggle to disassociate biochemistry (hypothyroidism) from autoimmune etiology (Hashimoto’s, Graves’, etc.).
These are two different spectrums that overlap each other but do not always match perfectly. We all wish they’d match. They don’t.
Our shared antibodies across the spectrum mean we have a lot in common as autoimmune thyroid patients.
The four antibody quadrants: TPOAb, TGAb, TSAb, TBAb
The four major antibodies that cause thyroid disease can be used to describe four quadrants on the spectrum in my diagram where the four major antibodies are located.
Some scientists only name three antibodies. That’s because it’s common to join the two TRAb (TSH receptor-blocking antibodies) together.
However, the TSAb and TBAb have opposite effects at the TSH receptor: one causes hyperthyroidism, the other hypothyroidism. Sometimes, only one of them is expressed, not the other. Sometimes both are present and play a game of tug of war. In some rare people, they alternate over time. These are two extremely powerful, volatile antibodies. The blocking power of TBAb can achieve 100% TSH-binding inhibition. It deserves its own quadrant.
Scientific research on antibodies enable us to locate each disease in the spectrum as overlapping regions across two, three, or all four quadrants.
Each manifestation of autoimmune thyroid disease crosses over more than one antibody’s quadrant.
As individuals with AITD, each of us likely fits somewhere within one these four ovals.
Let’s zoom into the top half of the spectrum, where “pure” Hashimoto’s patients reside, those who do not have any TSH-Receptor antibodies.
Hashimoto’s thyroiditis is characterized by the thyroid peroxidase antibody, generally abbreviated TPOAb.
In older research they used to call the TPOAb “antithyroid microsomal antibody” or “Antimicrosomal antibody.”
The TPO antibody is the one most strongly associated with thyroid gland damage, but it can’t cause damage on its own. When the TPO antibody combines with inflammatory cytokines and other factors, it can cause a slow process of lymphocytic infiltration (thyroid fibrosis).
As explained by Hajd-Kacem et al, 2009:
- “Autoimmune thyroiditis is considered to be the result of immune response leading to aberrant infiltration of lymphoid cells (T and B lymphocytes with Th‐1 lymphocytes subtypes predominating) and destruction of thyroid follicles lymphocytes form germinal centres rounding follicular cells.”
- “The final outcome is fibrosis replacing normal thyroid parenchyma and hypothyroidism resulting to thyroid cell destruction.”
- “TPO is a very large globular molecule which catalyses the thyroid hormone synthesis by catalysing both the iodination of Tg [thyroglobulin] and the coupling of some of the iodotyrosyl residues to generate the thyroid hormones T3 and T4.”
- “TPO Abs are known to be involved in thyroid cell destruction through cytotoxic mechanisms mediated by the complement and the killer cells.”
In some people, TPOAb-mediated thyroid destruction is not so slow. In others, it’s so slow that it can take decades to kill a thyroid’s cells enough to require thyroid medication. That’s why a diagnosis of Hashimoto’s hypothyroidism becomes increasingly prevalent with age.
Some people never get to that point of requiring medication, but they still have the antibodies. That’s why 10-15% of people with other autoimmune diseases have TPOAb antibodies, and yet some of them never become hypothyroid (Fröhlich & Wahl, 2017).
It’s not technically correct to say that Hashimoto’s is only “hypothyroid,” because only “approximately 10% of those with positive TGAb and/or TPOAb have hypothyroidism” (Takasu & Yoshimura Noh, 2008). Therefore, the vast majority of people with Hashimoto’s antibodies are still euthyroid and might never require thyroid hormone medication.
The thyroglobulin antibody, TGAb, is often elevated as well, directed against the thyroglobulin protein found in thyroid tissue.
As explained by Hajd-Kacem et al, 2009, TGAb do not have a role in causing thyroid cell death:
- “Synthesis of tri‐iodothyronine (T3) and thyroxine (T4) follows a metabolic pathway that depends on the integrity of the Tg [Thyroglobulin] structure.”
- “Tg [Thyroglobulin] is one of the major aAgs [autoangigens] recognized by aAbs [autoantibodies] in AITD.
- However, “Tg aAbs are not able to activate complement and consequently do not have important biological effect in the pathogenesis of AITD.”
In summary, Hashimoto’s is a chronic and progressive disease causing fibrosis of hormone-producing “thyrocytes” or “follicular cells” through a process of gradual lymphocytic infiltration. That’s why Hashimoto’s used to be called CLT, Chronic Lymphocytic Thyroiditis.
But Hashimoto’s patients, you don’t “own” the pathology thyroid gland fibrosis because you’re not the only type of person with TPOAb antibodies.
Graves’ Disease and Atrophic thyroiditis patients can also suffer lymphocytic infiltration because we share your TPO and TG antibodies.
You may think you are a “pure” Hashimoto’s patient because all you’ve ever had tested is TPOAb and TGAb and you’re definitely hypothyroid. But later, as your hormone levels and/or TSH shift, you may eventually find out that you could actually be a combination Hashimoto’s + Graves patient, or you might become an Atrophic Thyroiditis patient.
Now, let’s look at the lower half of the spectrum, the Graves’ disease and Atrophic thyroiditis spectrum, which also includes some Hashimoto’s patients who have TSAb and/or TBAb antibodies. I’ve color-coded them with their usual biochemical hyperthyroid (pink) to hypothyroid (blue) manifestations:
These two major TSH-Receptor antibodies (TRAb) are extremely powerful, volatile, and can be immediate in their effect on living thyroid tissue.
As explained by Hajd-Kacem et al, 2009:
- “Anti‐TSH receptor autoantibodies (TSH‐R‐aAbs) [TRAb] are found in the sera of most patients with hyper‐ and hypothyroidism.”
- “TSH‐R‐aAbs that mimic TSH actions and stimulate thyroid cells are called TSH‐R stimulating Abs (TSAb), whereas those that block TSH actions are called TSH‐R‐blocking Abs (TBAb)”
Graves’ Disease (GD) is characterized by the dominance of the TSAb antibody, the stimulating variant of the TSH-Receptor antibody. Patients also express the other three antibodies as well.
A person can develop hyperthyroidism in weeks to months as TSAb stimulating antibodies overstimulate the thyroid gland even in the absence of TSH, and thyroid hormones gradually build up in bloodstream.
Remission is experienced in many Graves’ patients after therapy, and some patients manifest in Graves eye disease without overstimulating a thyroid gland, so some Graves’ patients are euthyroid.
It’s not technically correct to say that Graves’ Disease is always “hyperthyroid,” because Graves’ disease patients experience full remission, and a small minority can even flip-flop into hypothyroidism, and even come back again (see Graves + Hashi’s, below).
If your Graves disease goes into full remission to euthyroidism, and you can now live without any thyroid medication, it’s likely you’re either
- A Graves’ Disease hyperthyroid patient whose TSAb antibodies have now disappeared, and now you’re stable, or
- A Graves’ disease patient whose TSAb and TBAb are in balance with each other, blocking some TSH receptors while overstimulating others. But you’re balancing on the edge of a knife and your remission might not last. Relapse may occur.
Atrophic Thyroiditis (AT) is characterized by the TBAb antibody, the blocking variant of the TSH-Receptor antibody.
You can see its region in the lower-right quadrant of the diagram, in the blue oval.
A person can become swiftly and severely hypothyroid if TBAb block TSH from stimulating a healthy thyroid, and the thyroid hormones gradually clear out of the bloodstream.
The TBAb antibody is not enough to cause thyroid atrophy in all patients, so some people call the category “Blocking-type hypothyroidism” or “Hypothyroid Graves / Graves hypothyroidism” (the TBAb is often found in Graves patients, but it does not dominate over TSAb while they are hyper).
As explained by McLachlan & Rapoport, 2013,
- “TBAb-induced hypothyroidism should be distinguished from Hashimoto’s thyroiditis (HT).”
- “In some instances, a distinction between hypothyroidism caused by HT and TBAb may be difficult, because the humoral markers of HT, autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb), frequently coexist with TSHR antibodies.
- “Conversely, the detection of TBAb in a patient with destructive HT may not indicate the cause of hypothyroidism.”
- “The most important clinical feature that distinguishes TBAb induced hypothyroidism from HT is thyroid atrophy that occurs in the former at the onset of clinical disease.”
Remission can be experienced in “Graves-hypothyroid” patients whose TBAb antibodies disappear, as long as their thyroid gland is not too atrophied by TBAb or damaged by TPOAb-mediated fibrosis.
In others with AT, the TBAb antibody can persist. It just won’t disappear, though their thyroid stays healthy.
It’s like their thyroid is in a shielding bubble and neither TSH nor TSAb can stimulate it.
In other people with AT, the TBAb antibody, perhaps in combination with a third “cleavage” TSH-Receptor antibody (not shown on the diagram) and/or TPOAb and certain cytokines, can cause severe thyroid gland atrophy (shrinkage, volume loss) in addition to fibrosis, which of course leads to permanent hypothyroidism.
You may think you’re a “simple” Hashimoto’s patient, but you may have a severely atrophied thyroid gland and never know it, because hardly anybody orders an ultrasound to measure a gland that isn’t enlarged or nodular.
Misunderstanding the cause of thyroid atrophy
McLachlan & Rapoport explain,
- “Of course, thyroid atrophy and fibrosis can also occur in HT, but in long-standing disease, not at the time of clinical presentation.”
This is where the mistake has arisen that severe thyroid atrophy is “end-stage Hashimoto’s” or is a natural part of aging. No, it’s not. It’s mediated by the TBAb antibody, found in 10% of Hashimoto’s patients and of 25-75% of Graves’ patients.
“It has been suggested that atrophic hypothyroidism should be an end-stage disease of Hashimoto’s disease. This was not supported by our findings because we found no difference in age or duration of symptoms between the groups with different thyroid volumes.” (Carlé et al, 2009).
Here are the facts:
- Thyroid atrophy can occur at any age whatsoever, so it’s not caused by age.
- Some people present with atrophy upon diagnosis, so it’s not caused by a long duration of hypothyroidism.
- The vast majority of Hashimoto’s patients do not experience any gland atrophy at all, living to an advanced age with a normal sized or slightly enlarged thyroid gland.
Here’s why there’s misunderstanding and confusion about thyroid atrophy.
During hypothyroid therapy, the TBAb antibody attack can be stealthy. Imagine a Hashimoto’s patient who continues to undergo slow TPOAb fibrosis during therapy. Their gland will be expected to reduce function over the years due to slow fibrosis. This gland pathology is rarely noticed because the person is already hypothyroid and on thyroid therapy.
Once the thyroid gland is mostly inert, atrophy may occur as an extreme “flare” of TBAb that in some people, shrivels the thyroid to radically reduce its volume.
Which patient will ever obtain a TBII test to find out why they suddenly became _more_ hypothyroid while on thyroid therapy? Just give them a higher dose.
Takasu’s research team has found that most TBAb antibody flares last less than a few years: the antibodies can attack, cause severe hypothyroidism by blocking TSH stimulation, may or may not cause atrophy, and then say goodbye. TBAb simply does not last long enough in blood to prove it is the cause of atrophy in all atrophic thyroid patients.
However, we have known enough since the 1980s to point the finger at TBAb. The TBAb is far more frequently found in atrophic than goitrous hypothyroid patients, but they didn’t understand why the antibody causes atrophy in some people but not others (Takasu et al, 1987).
A study that induced a TSH-receptor blocking antibody in hamsters in 2003 confirmed this antibody as a cause of thyroid atrophy. Thyroid specimens examined under a microscope showed characteristic thyroid gland cell changes seen in human atrophic thyroiditis, and “These changes were most evident in the hamster with the strongest blocking TSHR-Ab. Thus, we concluded that such thyroids were atrophic due to blocking TSHR-Ab.” (Ando et al, 2003).
In addition, the TBAb antibody may be assisted by the co-presence of the “cleavage” or “neutral” TRAb antibody, which signals cell death (apoptosis), especially when the TSAb is absent (Morshed et al, 2018).
Because of the difficulty of catching TBAb in the act of thyroid atrophy and understanding the mechanisms, many doctors have misidentified atrophy with age or the “end-stage” of Hashimoto’s.
Remission from Hypo-Graves
You may be an AT patient who is already in full remission right now even while you’re on thyroid hormone therapy. This could be you, if you have gone through a temporary phase of TBAb-caused hypothyroidism that didn’t shrink your thyroid, and perhaps TPOAb have not caused extensive thyroid fibrosis, either. If your ultrasound shows little to no damage to your thyroid gland, it may be healthy enough to sustain you. You may in fact be able to wean off of thyroid therapy (cautiously and gradually).
Lucky you! Maybe an autoimmune protocol diet change helped bring about remission, but you can’t attribute it all to your diet. Science shows the TBAb antibody simply disappears in most people, and they don’t mention any dietary change common to those in whom it disappears.
Continue reading on Page 2:
- Graves’ + Hashimoto’s combo
- Hi, I’m Tania S. Smith, an Atrophic Thyroiditis Patient.
- When seeing autoimmune thyroid disease, we don’t need a hierarchy.
- Instead, we need a telescope and a map.
Go to to Page 2 of article
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