The brief history of Hashimoto’s treatment

Hashimoto’s was first medically described in 1912. For the most of it’s brief medical history Hashimoto’s was considered to be only an underactive thyroid disorder. Treatment for underactive thyroid started more than a century ago.

Today we are still a long way from the perfect treatment solving all of the symptoms for each and every one of us, but we have seen some tremendous advancements making it possible for the most us to have focused and productive lives. And the future brings some promise too.
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A century worth of thyroid replacement

In the early days of treatment, at the end of 19th and the beginning of 20th century, scientists found out that lost thyroid function can be compensated for by adding an external thyroid. Many of the severe symptoms, including death could be prevented by this discovery.

Before the 1920s, thyroid treatment started with natural thyroid preparations from cow or pig. It came in several forms: transplanted thyroid, injection of thyroid cells or eating a raw thyroid (“thyroid feeding”).
Cow and pig thyroid glands were used as the first treatments for an underactive thyroid. Nowadays they are used for the production of natural thyroid medications.

While transplantation worked for some people, the others got their symptoms back and needed to undergo series of transplantations to keep them from dying [1].

The next treatment step was injections with, and eating of, pig and cow thyroid. This was a good success, and remained a treatment option for a couple of decades [2, 3, 4].

The most frequent problem during these early days was overtreatment. Lab diagnostics could not measure levels of thyroid hormones, the chemical structure and the exact functionality of thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) was still not known. As a consequence the treatment could not be adjusted appropriately. Without this knowledge it was also impossible to produce a synthetic version of the hormone in the lab.

The rise of Levothyroxine

The breakthrough in underactive thyroid treatment happened after the discovery of the structure of T4 and understanding that our body is able to convert T4 to T3. This was in the 1950s, and marked the start of Levothyroxine (T4) therapy [5]. Even today, this is a major therapy approach to restore low thyroid hormone levels.

Levothyroxine became the first prescription choice for doctors in the 1970s and the medical community worked under the assumption that Levothyroxine was the one-cure-fits-all solution. However, it quickly became apparent that the drug didn’t work for a pool of people. In the beginning, the remaining symptoms in patients were attributed to other diseases, or it was believed that patients were not compliant to the therapy [6].

With more research on the functionality of Levothyroxine it became apparent it was good for restoring blood levels of TSH to what was considered a “normal” or an average value. However, it did not fully re-activate the metabolism. Metabolism was 10%- 20% less efficient, resulting in problems with maintaining healthy weight [7, 8]. Another issue were high cholesterol levels, often experienced in hypothyroidism, which did not improve with Levothyroxine treatment [9, 10].

Levothyroxine is not a silver bullet

1 in 10 of people with hypothyroid condition cannot convert T4 into T3 because of a faulty enzyme called deiodinase [11, 12]. Enzymes are big molecules necessary for many of the chemical reactions in our body. Deiodinase removes one of the four molecules of iodine from T4, and by this process it turns it into an active hormone T3, containing three molecules of iodine.

Even for people who do not have the deiodinase-caused problem, symptoms such as fatigue, depression and anxiety remained [6]. This state is caused by a disturbed balance between T3 and T4, triggered by high T4 levels coming from Levothyroxine treatment. Maintaining healthy balance is necessary for proper functioning of the whole body, and this is why a combination therapy of T3 and T4 could be a better approach, improving mood and mental well being [6]. However, studies on different treatments still have conflicting results [11, 13-15].

All this knowledge helped research to understand an increased need for a more personal approach to treatment [11].

What about non-hypothyroid Hashimoto’s problems?

Lastly, we come to the unsolved part of Hashimoto’s: the immune system. While Hashimoto’s is an autoimmune disease, it is not treated as one.

How to treat Hashimoto’s?

Is cortisone an option? Cortisone was effective in other autoimmune diseases [16], but what about Hashimoto’s ?

The problem with cortisone is it’s massive side effects that might outweigh the benefit of the treatment. Side effects include water retention, swelling of arms and legs, heart problems, problems with mood, memory and other behaviors, weight gain, glaucoma, high blood sugar (which can trigger diabetes), osteoporosis (bone thinning) and slower wound healing. For that reason doctors will not likely prescribe a long-term cortisone treatment. Short term treatment also has side effects, but they will disappear after discontinuing the therapy [17].

Are there other options?

Is there anything that would allow our immune system to start resembling normally balanced and healthy system? In biology this is sometimes called re-programming. When the immune cells that have one function are basically re-educated and retrained to do another job. This re-programming can be done in several ways.

EPIGENETICS

Environment triggers autoimmune diseases without changing or mutating our DNA, this is called epigenetics [18–21].

Epigenetics determine how our genetic code (DNA) is read and made into a functional protein. Epigenetic changes are responsible for a fast adaptation to the new environment, but also for a rapid onset of some diseases.

Many drugs modifying our epigenome are in use, usually for treatment of cancer, but are considered for the treatment of some of the other diseases [22].

MICROBIOME

We could try changing our immune system through changing the amount and the type of bacteria we have in our intestines [23–25].

PARASITES

Parasites such as worms are successfully used for treatment of some other autoimmune diseases [26, 27]. They have also been shown to work successfully for fighting seasonal allergies.

STEM CELLS

Stem cell therapy would be a modern take on one of the historical treatments of transplanting an entire thyroid. With today’s sophisticated technology, we could easily get a stem cells transplant. This type of transplantation would not be a classical organ transplant and would not require a major surgery. It would more resemble a vaccination, where cells would be in a syringe and injected into the thyroid.

Before we can explore these approaches, we will have to wait a bit, but what we can do is try to limit the impact of the environment. To do this, it is important for you to know what personally works for you. Remember that what works for you might not work for the others in part or the entirety. The opposite applies too, don’t be discouraged if someone else’s silver bullet does not work for you.

Conclusion

How did the treatment on underactive thyroid advance through time. Adaptation from McAninch et al (2016).

Hypothyroid treatment history was so far short and interesting. It resulted in a development of two main types of treatment: a single hormone therapy (monotherapy) with synthetic Levothyroxine, and a combination of T3 and T4 therapy. The combination therapy can be given as a combo of synthetic Levothyroxine (T4) and Liothyronine (T3) or as a natural thyroid preparations.

Natural thyroid preparations are coming back to use, since scientists have solved the issues of their short shelf life and have significantly improved storage sensitivity, and batch variability [28]. Also, it became apparent that the initially reported side effects (angina, heart failure, palpitations, nervousness, tremor and perspiration) might not come from the natural thyroid preparations themselves, but from their incorrect dosage [29–31].

Levothyroxine is still the prefered therapy choice for most of healthcare professionals. However medical community increasingly accepts patient diversity, therefore the treatment and disease management should become more personalized. It will be exciting to see what new treatments will emerge in the years to come.

References:

1. Kocher A. The treatment of hypothyroidism by thyroid transplantation (1923).

2. Lundie R.A. The treatment of myxoedema (1893).

3. Ord W.M. et al. Clinical remarks on certain changes observed in the urine in myxoedema after the administration of glycerine extract of thyroid gland (1893).

4. Mackenzie H.W. A case of myxoedema treated with great benefit by feeding with fresh thyroid glands (1892).

5. Chalmers J.R. et al. The synthesis of thyroxine and related substances. Part V. A synthesis of L-thyroxine from L-tyrosine (1949).

6. Hoffenberg R. Primary hypothyroidism (1978).

7. Cotton G.E. et al. Suppression of thyrotropin (h-TSH) in serums of patients with myxedema of varying etiology treated with thyroid hormones (1971).

8. Gorman C.A. et al. Comparative effectiveness of dextrothyroxine and levothyroxine in correcting hypothyroidism and lowering blood lipid levels in hypothyroid patients (1979).

9. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation (2002).

10. Tanis B.C. et al. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies (1996).

11. Jonklaas J. et al. American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014).

12. Wiersinga W.M. et al. 2012 ETA guidelines: the use of L-T4 + L-T3 in the treatment of hypothyroidism (2012).

13. Saravanan P. et al. Psychological well-being in patients on ‘adequate’ doses of l-thyroxine: results of a large, controlled community-based questionnaire study (2002).

14. Hoang T.D. et al.. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study (2013).

15. Wiersinga W.M. Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism (2014).

16. Fauci, A. S. Corticosteroids in autoimmune disease (1983).

17. Buchman, A. L. Side effects of corticosteroid therapy (2001).

18. Hewagama A. et al. The genetics and epigenetics of autoimmune diseases (2009).

19. Farh K. K. et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants (2015).

20. Brooks W. H. et al. Epigenetics and autoimmunity (2010).

21. Tomer Y. Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics (2014).

22. Heerboth S. et al. Use of epigenetic drugs in disease: an overview (2014).

23. Round J. L. et al. The gut microbiota shapes intestinal immune responses during health and disease (2009).

24. He B. et al. Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors (2017).

25. Campbell A. W. Autoimmunity and the gut (2014).

26. Correale J. et al. Association between parasite infection and immune responses in multiple sclerosis (2007).

27. Correale J. et al. Helminth infections associated with multiple sclerosis induce regulatory B cells (2008).

28. Kaufman SC, Gross TP, Kennedy DL. Thyroid hormone use: trends in the United States from 1960 through 1988 (1991).

29. Williams R.H. The thyroid (1955)

30. Frawley T. F. et al. Metabolic and therapeutic effects of triiodothyronine (1956).

31. Smith R.N. et al. Controlled clinical trial of combined triiodothyronine and thyroxine in the treatment of hypothyroidism (1970).

Infographics references:

1. McAninch, E.A. et al. The History and Future of Treatment of Hypothyroidism (2016).

2.https://www.zf.jcu.cz/copy_of_dokumenty/dokumenty-journal-of-agrobiology/2011-number-1/Peksa_imprim_web.pdf

3. http://centraldrugsrx.com/pdf/Thyroid_Conversion_Chart_08-13a.pdf