Stories of complete remission from autoimmune hypothyroidism circulate on internet forums.
Stories of significant fluctuations in thyroid status that allow one to reduce thyroid medication or require a major increase—these also circulate.
I suspect most autoimmune hypothyroid and hyperthyroid patients have dreamed of a full remission rather than dependency on lifelong medical treatment.
As I write this during early COVID-19 virus era, I too wish I had my healthy thyroid back. Then I would not have any worry about the supply of my thyroid medication or risk of reduced access to good thyroid health care and thyroid testing.
On the other hand, “fluctuations” in thyroid status are not very desirable at this time, since the medical system and laboratories may be poorly equipped to manage safely the changes in dosage that would be required.
So, how common are remission and fluctuation in thyroid status? They are more common in autoimmune thyroid disease than most people realize.
This article provides scientific evidence that these tales of autoimmune remissions and even “flip-flops” between hyper- and hypothyroidism do occur.
However, remissions and fluctuations in thyroid status do not occur for the reasons that many people say they do, namely, the reduction and/or disappearance of TPOAb or TGAb antibodies.
A more powerful set of thyroid antibodies are responsible for swift and extreme thyroid status fluctuations.
In this post, I’ll share scientific information about the two TSH-Receptor antibodies (TRAb):
- the TSAb (stimulating) antibody and
- the TBAb (blocking) antibody
These can be found in all three subtypes of autoimmune thyroid disease: Hashimoto’s thyroiditis, Graves’ Disease, and Atrophic thyroiditis.
These TRAb antibody levels can fluctuate widely and unexpectedly, and when they do, they can immediately begin to affect thyroid biochemistry. They can produce a significant change in thyroid status within weeks or months. They can cause a complte flip-flop from hypo to hyper or vice versa. They are different from what’s known as “Hashitoxicosis.”
After equipping you with with understanding and examples, I conclude with tips about safely discovering whether you might be in remission while on therapy for hypothyroidism.
It’s best to be aware of these antibodies’ existence in case an extreme fluctuation in thyroid status happens to you someday, or happens to someone you know.
Background: The TPOab and TGAb antibodies
Before further discussing the lesser-known TRAb antibodies, it can be helpful to further characterize the much better known TPO and TG antibodies.
These are the most commonly tested antibodies in autoimmune thyroid disease (AITD). You can see them in the upper half of this AITD spectrum diagram:
Thyroid Peroxidase antibody (TPOAb) and Thryoglobulin antibody (TGAb) are commonly referred to as “Hashimoto’s antibodies.” However, they can be present in patients with all types of autoimmune thyroid disease, as shown in the table below.
None of the anti-thyroid antibodies are exclusive to only one subclass of autoimmune thyroid disease patients.
NOTE: In the table, TSHR-Ab are TRAb, and “Autoimmune thyroiditis” includes both Hashimoto’s and Atrophic thyroiditis.
TPOAb can destroy thyrocyte cells (also called “follicular” cells) in the thyroid gland, but “their contribution to thyroid damage compared to T cell and cytokine-mediated apoptosis is minor” (Fröhlich & Wahl, 2017).
These TPO antibodies can’t directly destroy much thyroid tissue without inflammatory cytokines, and high levels don’t necessarily increase the speed of thyrocyte cell death and thyroid fibrosis (lymphocytic infiltration) that is a characteristic hallmark of advanced Hashiomoto’s thyroiditis.
In addition, few realize that not all TPO antibodies are alike in function. Apparently TPOAb derived from Hashimoto’s patients can block thyroid peroxidase activity in thyroid cells, but TPOAb derived from healthy people’s blood does not (Fröhlich & Wahl, 2017). Yet both show up in antibody tests.
This is why one may even find people with perfectly balanced thyroid hormones without any need of thyroid therapy, despite elevated titres of TPOAb—in some people, these antibodies do not possess the characteristics that cause harm, and even when they do, thyroid damage requires certain cytokines and T cells to be involved, not just TPOAb.
In contrast to TPO antibodies, TG antibodies do not cause thyroid cell death. Instead, they appear to be an outcome and indicator of a thyroid disorder: TGAb levels tend to increase as thyroid damage occurs, or in the presence of thyroid tissue as iodine intake increases and/or TSH rises (Fröhlich & Wahl, 2017).
Hashimoto’s can certainly cause permanent and severe hypothyroidism. After the thyroid gland is very damaged by autoimmune fibrosis, antibodies may or may not fall to lower levels within the laboratory’s stated reference range.
TPOAb reduction alone does not cause remission except in very mild cases of subclinical hypothyroidism, and truly subclinical cases mean they are not yet symptomatic and do not usually require thyroid therapy.
It is true that TPOAb (thyroid peroxidase antibodies) are necessary for the type of thyroid cell death and and fibrosis (lymptocytic infiltration) in Hashimoto’s. It is also true that TGAb (thyroglobulin antibodies) are found in many people with autoimmune thyroid disease.
However, changes in TPOAb and TGAb antibody levels have a very indirect and slow impact on and correlation with gland health and biochemistry. They are simply not capable of bringing about remissions that drastically improve independent thyroid gland function within months or a few years.
Reducing those antibody levels may halt or slow down the progression of thyroid disease while you use other means to optimize the thyroid function that remains. But that is not the kind of “autoimmune remission” with return of normal biochemistry on no medication that I have in mind here.
In more extreme cases where patients require thyroid hormone medication, even if TPOAb were to completely disappear, the person may remain in a hypothyroid state without medication because the thyroid gland is damaged beyond the ability to sustain healthy thyroid hormone levels.
Therefore, one must look to other antibodies to understand significant remissions and fluctuations in thyroid status.
What are the TSAb and TBAb antibodies?
When the pituitary gland secretes Thyroid Simulating Hormone (TSH), the TSH enters the TSH Receptors in the thyroid gland, which stimulates a healthy thyroid to secrete T4 and T3 thyroid hormones.
If your body is genetically predisposed to produce antibodies to the TSH Receptor, you will likely have several of the many genetic SNPs that are highly associated with Graves’ disease.
If this response is triggered, there are two types of TRAb antibodies your body may form:
- TSAb. This enters the receptors and mimics TSH. These antibodies stimulate thyroid cells even in the absence of TSH. These are the antibodies that commonly cause Graves’ Disease manifesting as hyperthyroidism.
- TBAb. Thisblocks the TSH receptor so that TSH in circulation cannot enter it, preventing thyroid cells from being stimulated. These are the antibodies that cause transient Graves’ hypothyroidism as well as partial or severe Atrophic Thyroiditis.
The two TSH receptor antibodies “attack” the receptor for TSH in two different ways, by stimulating it (as an “agonist”) or blocking it (as an “antagonist”).
As explained by Takasu and Matsushita (2012),
“Some patients may have TBAb and TSAb simultaneously or sequentially. The balance of TBAb and TSAb determines whether a patient has hypothyroidism or Hyperthyroidism.”
In other words, you can have both blocking and stimulating antibodies in circulation at the same time, contradicting each other.
These two antibodies can fluctuate in their levels, and one or the other or both can entirely disappear over time.
Prior to any treatment or significant damage to the thyroid gland, the net effect of the two antibodies on thyroid tissue will determine your biochemical status:
- Hypothyroid (if TBAb dominate) as TSH receptors are blocked,
- Euthyroid (if both are equally present, or both disappear),
- Hyperthyroid (if TSAB dominate) as TSH receptors are overstimulated
Both the stimulating and blocking antibody may be found in patients with Graves’ Disease, resulting in an internal tug of war between some antibodies that block some TSH receptors while other antibodies stimulate other TSH receptors.
Both types of TRAb antibodies (TSAb and TBAb) are considered Graves’ Disease antibodies.
Although the term “Graves’ Disease” was initially intended to describe only the hyperthyroid manifestation of TRAb antibody activity, “Graves hypothyroidism” is a term used in more than one scientific research article that discusses this antibody’s activity.
TRAb antibody prevalence statistics
In 2017, Fröhlich and Wahl’s review of thyroid autoimmunity research reported that “Anti-TSHR antibodies have been found in
- 90% of GD [Graves’ Disease] patients,
- 0–20% of HT [Hashimoto’s Thyroiditis patients],
- and 10–75% of atrophic thyroiditis patients.”
Up to 20% of all Hashimoto’s patients worldwide is a significant number of people that could have Anti-TSHR antibodies.
Diana et al’s 2017 article on the prevalence of TBAb alone (not TSAb) in 1,079 patients with Hashimoto’s and Graves’ disease, found a 9.3% prevalence in Hashimoto’s and a 4.2% prevalence in Graves’ disease.
Fröhlich and Wahl’s review found that in Graves’ patients, stimulating antibodies were more common, as expected. However, their report said TBAb were far more frequent than Diana et al discovered:
- “Stimulatory antibodies [TSAb] have been found in 73-100% [of Graves disease patients] and
- Blocking anti-TSHR antibodies [TBAb] in 25-75% of GD patients.”
The next question is, “Who is more likely to have the Blocking antibodies (TBAb), people classified as Hashimoto’s or people classified as Graves’ patients?”
According to a later study focusing on the TBAb by Diana et al, 2017,
- 82% of people with positive TBAb are Hashimoto’s patients
- 18% of people with TBAb are Graves patients.
Another useful question to ask is “Why do the prevalence statistics above range so widely (0-20%, 10-75%)”? Beyond the obvious reason that Fröhlich and Wahl were synthesizing data from many different studies:
- “The variations in detection appear to be linked to the type of assay that has been used.” (Fröhlich & Wahl, 2017). There are several assay technologies for these antibodies: The TRAb test, TSI test, TBII test, and specific TBAb tests. Each varies in sensitivity toward the blocking or stimulating TSHR antibody. Few tests measure the blocking antibody.
The TBII test (thyrotropin-binding inhibitor immunoglobulin) is a very useful and cost-effective way of screening for both TSHR antibodies at the same time. The TBII is a “2-in-1” test; it does not differentiate between blocking and stimulating, but it adds both titres together in one number. Its combined results achieve a “sum” that has prognostic significance, according to Diana et al, 2016 & 2018.
- Antibody levels can fluctuate and even disappear over time. However, few studies last long enough to catch the antibodies in the act by measuring many times over many years.
- The number of patients and the methods they used to recruit and exclude them will differ from study to study.
- Each study may define thyroid status differently. There are at least four ways to define thyroid status.
The “0-20%” incidence of TSHR-Ab in Hashimotos is so variable because Atrophic thyroiditis (AT) is misunderstood. Often, Atrophic Thyroiditis patients are simply misclassified as simple cases of Hashimoto’s, when they are genetically and immunologically unique from “pure” Hashimoto’s.
I am an Atrophic Thyroiditis (AT) patient. My inadequate thyroid therapy and misunderstanding of my abnormal biochemistry and symptoms caused harm. My complete, correct diagnosis was delayed. This drove me to research the condition thoroughly in light of my experience and health data. Long ago, I wrote a separate post that focuses on AT.
Some of the statistics may seem very contradictory and confusing.
Admittedly, it is impossible to be biochemically hyper and hypo at the same time—either your T4 and T3 supply is excessive in blood right now, or it is deficient in blood right now.
However, “Graves’ disease” is not a true synonym for “hyperthyroidism.”
“Graves disease” is simply the diagnosis of a lifelong autoimmune thyroid disease that is caused by TRAb antibodies, which may or may not manifest in episodes of biochemical hyperthyroidism.
Similarly, “Hashimoto’s thyroiditis” is not a true synonym for “hypothyroidism,” but rather a diagnosis of an autoimmune thyroid disease caused by TPOAb antibodies.
A patient with a clear Hashimoto’s diagnosis will have elevated TPOAb and signs of thyroid gland damage revealed in high TSH and/or low FT4 levels prior to thyroid therapy.
But Hashimoto’s is not the only cause of thyroid hormone deficiency. One can have hypothyroidism from lack of TSH stimulation of a healthy thyroid (which is called “central hypothyroidism”) or from severe iodine deficiency.
A person can also have subclinical Hashimoto’s if TPOAb antibodies are present and TSH is elevated while the gland is not yet damaged enough to reduce FT4 levels and require thyroid hormone therapy.
A “pure” and uncomplicated case of Hashimoto’s (one in which Graves’ antibodies are not also present) will not also have measurable TRAb showing up on a TBII test (the test that can reliably detect the TBAb blocking antibody).
Simplicity exists when there is consistency across the four definitions of thyroid status I’ve discussed in a previous post. The naming of Graves’ and Hashimoto’s is more comfortable when 1) the symptoms and signs in bodily tissues, 2) the biochemistry and 3) the gland health all line up with the 4) etiology (cause), the usual set of antibodies.
Therefore, it is common for Graves’ disease patients to have both TPOAb and TGAb as well as TRAb. However, Graves’ patients do not usually become diagnosed with Hashimoto’s unless they later present with biochemical hypothyroidism and lymphocytic infiltration of the thyroid gland.
If a Hashimoto’s patient tests negative on TRAb but has a genetic susceptibility to Graves’ disease, there is nothing but a set of environmental triggers preventing them from having had TRAb in the past or acquiring TRAb and Graves disease in the future.
But in thyroid disease, things are not simple under the surface. Sometimes that complexity manifests itself in surprising ways. “Complex” diagnoses of “Graves + Hashimoto’s” do exist. The diagnosis of Graves does not necessarily exclude Hashimoto’s or vice versa.
An example of a complex diagnosis
A hypothyroid Hashimoto’s patient may have a partly damaged thyroid gland that still secretes some thyroid hormones. During thyroid therapy, their TSH, FT4 and FT3 levels fluctuate unreasonably over time due to undiagnosed TSAb and/or TBAb antibodies. This person has been on the same or slightly adjusted dose of thyroid hormone when suddenly, within even a short interval such as 3 months between tests, they appear to have had a significant boost or loss of FT4 and a related shift in FT3 levels.
Why did their FT4 change so much and so suddenly without reason?
The clinician and patient must reason that there are only two places T4 hormone can come from: 1) thyroid hormone medication, or 2) the thyroid gland. Sometimes these FT4 shifts are so extreme that they cannot be explained by other reasons, such as changes in LT4 medication absorption, or a long list of variables that can interfere with thyroid biochemistry (medications, supplements, fasting / obesity, secreting thyroid nodules or growths, or illnesses). A good clinician will be aware of the degree of T4 fluctuation that is likely to be caused by such changes.
Perhaps the best hypothesis that remains is a variable rate of thyroidal T4 and T3 secretion due to TRAb antibody fluctuation. As long as some living thyroid tissue remains, the gland’s secretion can be powerfully manipulated by fluctuating TSH-Receptor stimulating and blocking antibodies—whether a person is on thyroid therapy or not.
In this case, the evidence to confirm the hypothesis about the source of the extra T4 or loss of T4 would be found in the appropriate antibody test.
Stats from a 10-year longitudinal study
In 2012, Japanese researchers Takasu and Matsushita reported on the antibody status and thyroid status of 132 patients with Graves’ disease antibodies, many of whom changed between hypothyroid, hyperthyroid and euthyroid (healthy) thyroid status over 10 years.
On the HYPO-thyroid side
Takasu and Matsushita found:
- 50% (18) of the 34 hypothyroid people with TBAb antibodies remained hypothyroid.
- 44% (15) of the 34 hypothyroid people had their TBAb antibodies disappear.
- 87% (13) of the 15 hypothyroid people whose TBAb antibodies disappeared recovered from hypothyroidism (remission in 13/34, or 38% of those with TBAb).
NOTE: Takasu & Matsushita use the abbreviation “TSBAb” instead of the now recommended TBAb nomenclature (Kahaly & Diana, 2017), so I have updated it throughout.
The thyroid gland size of the hypothyroid patients made a huge difference in the likelihood of remission. Takasu’s publications repeatedly claim that TBAb antibody “causes atrophy” of the thyroid (Atrophic Thyroiditis, AT). In AT patients whose glands have lost a significant amount of volume, hypothyroidism appears to be difficult to reverse even if the TBAb disappear.
However, Takasu and Matsushita offer reason to hope for remission in Hashimoto’s Thyroiditis (HT) patients whose glands show neither extensive atrophy nor fibrosis. If indeed their hypothyroidism is caused only by transiently high TBAb, it is fully reversible:
- 100% of the 10 TBAb-positive Hashimoto’s patients (“goitrous thyroiditis”) with TBAb recovered from hypothyroidism.
- 21% (5) of the 24 TBAb-positive Atrophic Thyroiditis (“non-goitrous thyroiditis”) patients recovered from hypothyroidism. Apparently their gland had not thoroughly atrophied yet.
The main problem with thyroid therapy is understanding the hypothyroid side of this spectrum.
- Very few people except rare researchers (such as Diana et al, 2017, 2019) advocate for performing TBAb-sensitive tests on hypothyroid “Hashimoto’s” patients, approximately 10% and up to 20% of whom have this antibody.
- It is puzzling why so few clinicians want to detect whether, in a given patient, the TBAb blocking antibody is responsible for an initial swing to the extreme hypo side. Extremely high TSH always results in being placed on thyroid therapy without any question as to the true cause of the hypothyroidism. Treatment before diagnosis puts the cart before the horse.
- Research indicates this TBAb antibody’s disappearance is largely responsible for remission to euthyroidism in those who have a healthy thyroid gland that has been temporarily blocked from receiving TSH signals.
On the HYPER-thyroid side
Remission is even more common in hyperthyroidism than in TBAb-induced hypothyroidism. This is likely because Graves’ disease TSAb antibodies, when they outnumber “cleavage/neutral” TSHR antibodies, can reduce thyrocyte cell apoptosis (Fröhlich & Wahl, 2017).
Basically, remission is possible because the stimulating antibodies can keep your thyroid cells from dying.
Takasu and Matsushita’s 10-year study (2012) found:
- 10.2% (10) of the 98 hyperthyroid people with TSAb antibodies remained hyperthyroid.
- 74% (73) of the 98 hyperthyroid people had their TSAb antibodies disappear.
- 82% (60) of the 73 hyperthyroid people whose TSAb antibodies disappeared recovered from hyperthyroidism (remission in 60/98, or 61.2% of those with TSAb).
An earlier study on hyperthyroid remission rates
In 1990, Burrow, Oppenheimer & Volpe reported high remission rates from hyperthyroidism in Graves’ Disease, regardless of the presence of antibodies:
- “The incidence of remission following thionamide drugs … between 31 and 77% from 1950 to 1973.”
- After “a short-term antithyroid drug regimen … 46% remission rate”
- “This rate of remission exceeds that seen with propranolol quite significantly, where the remission rate has been reported to between 22 and 36%.” (p. 239)
There is also hope for some hyperthyroid patients to eventually achieve stable euthyroid status without therapy. Burrow, Oppenheimer and Volpe also noted that
- “Relapses after remissions occur in about half of patients.”
- Then, “following a single course of antithyroid drugs, 23% had a return of hyperthyroidism by the end of 3 months.”
- However, after 3 more months, “the rate of relapse progressively declined, and by the end of 4 years, 57% were still well.” (p. 239)
Pregnancy and hyperthyroid remission
In addition, pregnancy can induce Graves’ disease remission, according to Ando, et al, 2008:
- “The thyroid autoimmune response diminishes during pregnancy, resulting in remission of GD in the vast majority of patients.”
“However,” they go on to state, “some patients with more severe disease and high levels of TSHR-Abs have persistence of these antibodies into the third trimester.”
Continue to Page 2 to read:
- Flip-flops between hyper and hypo
- Hashitoxicosis versus transient TSAb
- Understand the full spectrum
- Tips: Do you still need thyroid medication?