Graves’ disease patients routinely get tested for the TSH-Receptor antibody (TRAb) when they become hyperthyroid.
Hashimoto’s patients with TRAb antibodies, on the other hand, are overlooked. Just how many of us are being overlooked in various countries?
The thyroid-stimulating antibody seen in Graves’ disease is only one of two TSH-Receptor antibodies:
- TSAb stimulates the TSH receptors, and
- TBAb blocks the TSH receptors.
Many Hashimoto’s patients will never get properly diagnosed because people mistakenly think TSH-Receptor antibodies are only found in Graves’ disease.
How many people are likely to experience the mysterious impacts of this antibody, such as:
- transient hypothyroidism with a partial or full remission
- severe and permanent thyroid atrophy at an early age
- wide biochemical fluctuations during hypothyroid therapy
- confusing flip-flops between hyperthyroid, euthyroid, and hypothyroid states
- and disorders and symptoms caused by TSH receptor signalling interference in tissues beyond the thyroid gland?
I’ve just outlined these things in my previous article on remissions and fluctuations in autoimmune thyroid disease.
How many of their doctors will be clueless as to why we are enduring these things? What will they mistakenly attribute them to? aging, stress, or other diseases?
Two antibodies. Two types of autoimmune thyroid patients. Only one antibody in one type of patient is being tested.
Therefore, we are currently overlooking the diagnosis of 3 out of 4 cases.
Approximately how many human beings are in each of those 3 cases?
Specifically, how many people in Canada, the UK, the US, and Australia are not getting tested or diagnosed?
Do the overlooked Hashimoto’s patients with TRAb outnumber Graves’ disease patients with TRAb, since the population with Hashimoto’s is many times larger than the population with Graves?
Fortunately, we have the published research data to make some estimated calculations.
In this article, I’ll walk you through my tables and graphs of synthesized data, and I’ll discuss the implications.
The Prevalence of Graves’ and Hashimotos
Fröhlich & Wahl, 2017 give the number cases population:
- “Data from Europe, North America, Australia, New Zealand (defined as area 1) and
- Asia, Middle East, Caribbean, South America (defined as area 2)
differ in the reported prevalence (cases/100,000 individuals) of the most frequent AD (1) as follows:
- Graves’ disease (GD, area 1: 50–626, area 2: 20),
- Hashimoto’s thyroiditis (HT, chronic autoimmune thyroiditis, autoimmune hypothyroidism, area 1: 300–2,980, area 2: 350)”
Based on the low and high estimates in Area 1 regions, their Hashimoto’s patient population is 4.76 to 6 times larger than the Graves’ disease population.
In other words, for every Graves’ patient, there are 4.76 to 6 Hashimoto’s patients in these Area 1 regions.
The prevalence of both diseases in for Area 2 regions is lower in real numbers, but the ratio is more extreme: for every Graves’ patient, there are 17.5 Hashimoto’s patients.
If you translate Area 1 numbers into percentage of population, you get this table and graph:
Clearly, Hashimoto’s patients outnumber Graves’ patients.
Now let’s narrow it down to just the AITD patients with these antibodies.
Percentage of Graves’ and Hashimotos with TRAb
Diana et al’s 2017 study found that among 1,097 autoimmune thyroid disease patients (357 with Graves’ and 722 with Hashimoto’s):
- 86.5% of Graves’ patients had the TSAb stimulating antibody.
- 4.2% of Graves’ patients had the TBAb blocking antibody.
- 9.3% of Hashimoto’s patients had the TBAb blocking antibody,
- 9.4% of Hashimoto’s patients had the TSAb stimulating antibody.
Next, let’s find out how many people are in each category based on four countries’ population data.
I’ve used the Area 1 higher estimates of prevalence in the population, and I’ve combined them with the stats on the percentage of Graves’ and Hashimoto’s patients with each TRAb antibody type.
Then I combined that data with four countries’ population statistics for “mid-2019” from the Population Reference Bureau in Washington, DC: https://www.prb.org/international/
In Canada, an estimated 188,178 Hashimoto’s patients are blessed with or cursed by fluctuating TSAb (an estimated 94,592 people) and/or TBAb (an estimated 93,586 people) but are never tested for them.
In addition, in Canada, an estimated 9,182 Graves’ disease patients are blessed or cursed with the TBAb blocking antibody that nobody cares to notice they have.
Looking at these numbers, does anyone still dare say that the blocking and stimulating antibody are “rarely” found in Hashimoto’s patients? .
The NIH Genetic and Rare Diseases Information Center says
“In the European Union, a disease is defined as rare when it affects fewer than 1 in 2,000 people.”
1 in 2000 people is 0.05% of the population.
Based on the Canadian population in 2019, 0.05% of the population was 17,350 people. The only “rare” subclass above is the number of Graves’ Disease patients who would test positive on a TBAb-specific assay, which would be estimated at 9,182 Canadians, shown in Table 3.
Percentages of the AITD-TRAb population
Next, let’s look at the percentages of these subclasses in relationship to each other.
Each grand total per country represents the “Autoimmune thyroid disease patients with TRAb antibodies” – which I’ll abbreviate “the AITD-TRAb population.”
Within this AITD-TRAb patient population, only 48.9% will routinely get their antibodies tested in diagnosis: These are the Graves’ Disease hyperthyroid patients who are tested for the TSH-Receptor stimulating antibody, TSAb.
The remainder of AITD-TRAb patients, 51.1%, will have their antibodies ignored.
- 48.7 % of the AITD-TRAB population are Hashimoto’s patients who won’t likely get tested
- 24.5% of the AITD-TRAb population are Hashimoto’s patients with TSAb stimulating antibodies
- 24.2% of the AITD-TRAb population are Hashimoto’s patients with TBAb blocking antibodies.
As for the number of people with each TRAb antibody subtype, roughly 3 out of 4 will have the stimulating variety, and 1 out of 4 the blocking variety:
- the TBAb blocking antibody is found in 26.5% of people in the AITD-TRAb population (almost all of them Hashimoto’s)
- the TSAb stimulating antibody expresses in 73.4% of people in the AITD-TRAb population (1/3 of whom are Hashimoto’s patients)
We are currently overlooking half the population thyroid patients with TRAb antibodies.
We are overlooking most of these people with antibodies just because they are TBAb blocking antibodies that cause hypothyroidism
Some TSAb stimulating antibodies we ignore because it’s a widespread belief that they can’t exist in hypothyroid people.
What are the implications?
Millions of neglected diagnoses worldwide translate to millions of people who may have increased suffering, health care costs, and unsolved medical mysteries.
But biochemical hypothyroidism is just one of the many manifestations of these antibodies.
Thyroidectomies and radioiodine ablation don’t remove the antibodies. There is no such thing as an antibody-ectomy.
Some therapies for Graves’ powerfully shift the antibodies and can aid remission, but it is not known if thyroid hormone dosing modulates them. Thyroid hormone dosing is a way we compensate for severe TBAb-caused hypothyroidism, but it can’t fix everything these antibodies can do.
By overlooking the blocking antibody in diagnostic testing, we are not using what Diana et al, 2017 calls “an important tool to identify AITD, mainly in the form of reversible hypothyroidism.”
In other words, we may have an unknown number of cases of TBAb-based hypothyroidism that will, or have already, slipped into remission.
What Diana et al fail to note is the bad news. The TBAb antibody can also cause permanent and severe atrophy of the thyroid gland, since these are the antibodies responsible for Atrophic Thyroiditis at any age. TBAb can make untreated hypothyroidism more dangerous, and its onset can be swift.
For some patients, TBAb-TSAb fluctuations are a tug-of-war that makes therapy very complicated and unpredictable: it can force them to cycle through phases of hyper, hypo and euthyroidism over months or years.
In addition, the antibody can cause tissue manifestations beyond the thyroid gland. Just as the Graves’ stimulating antibody activity manifests in eyes, skin, bones, thymus, even when fully euthyroid, the blocking one can as well. All tissues that express TSH receptors may interact with this antibody.
As for the cost of ignorance paid by medical research, consider all the ways in which thyroid therapy clinical trials can be compromised by these antibodies flaring up.
Consider the lack of clarity that will persist about relationships between thyroid autoimmunity and other health conditions. You can’t generalize about “autoimmune hypothyroidism” if 20% of people in this category are distinctly different from their peers in autoimmune etiology and prognosis.
by Tania S. Smith
Diana, T., Krause, J., Olivo, P. D., König, J., Kanitz, M., Decallonne, B., & Kahaly, G. J. (2017). Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease. Clinical & Experimental Immunology, 189(3), 304–309. https://doi.org/10.1111/cei.12980
Fröhlich, E., & Wahl, R. (2017). Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases. Frontiers in Immunology, 8. https://doi.org/10.3389/fimmu.2017.00521
Population Reference Bureau. [International population statistics]. https://www.prb.org/international/indicator/population/snapshot