Hypothyroidism is not a chronic disease in Canada

Thyroid disease is chronic, not cured

Why is hypothyroidism missing from Canada’s chronic diseases list?

I put the question mark over “thyroid disease” in the image because I can’t fit the long word “hypothyroidism” into our maple leaf or tagline.

The image raises the question — this post explains it in more detail.

Why focus on “hypothyroidism” within the broader category of “thyroid disease” in general?

Among the various types of thyroid disease, some are truly “chronic” while others are not.

Hyperthyroidism, thyroid cancer, and thyroid nodules are serious conditions and health crises (I do not mean to dishonor them), but they are not technically chronic diseases. This is because their unique features can be permanently resolved by partial or total thyroidectomy or in the case of hyper, by radioioidine therapy.

Infectious thyroiditis is temporary, and some forms of postpartum thyroiditis are temporary.

However, once a hyperthyroid person or thyroid cancer patient permanently loses their gland function, they now technically have a chronic disease.

A key feature of many chronic diseases is the loss of a vital gland and the resulting lifelong dependency on medication.

So, I ask again —

Why is hypothyroidism missing from Canada’s chronic diseases list?

Not every disease can be included on this list, but consider why some are and others aren’t. It’s a choice. It’s influenced by medical biases.

What makes a disease worthy of being on Canada’s list of chronic diseases?

What does it mean for citizens who have that disease to have their disease on that list?

What does it mean for doctors and researchers, or for society?

Here is one benefit we lack as thyroid patients. Chronic diseases get the attention of a lot of research by government and the agencies it funds. Health Canada keeps statistics on them.

Because thyroid diseases are not on this list, we currently have no idea how many people suffer from the various types and degrees of thyroid disease in all provinces and across Canada.

We are invisible.

People think we have merely a “managed biochemical condition” not a “chronic disease.”

There’s a lack of medical understanding of how our chronic disease interacts with other health conditions.

Consider Type 1 diabetes. Severely and permanently hypothyroid citizens are just as dependent on medication as a Type 1 diabetic is. An essential organ has failed.

Just like a Type 1 diabetic, our medication does not cure us. We remain at the mercy of pharmaceutical intervention for the rest of our lives, and our medication is too often maladjusted to our body’s needs. Moving from doctor to doctor can make a huge difference in effective vs. ineffective therapy, as well as access to hormone testing, and access to pharmaceutical choice.

Medicine thinks we no longer have hypothyroidism when TSH is normalized. We are now “euthyroid.” Even if our T3 or T4 is too low to enable optimal function. We are no longer “hypothyroid” by the TSH-based definitions. Our condition has been erased. We are now “well managed.”

This is the horrible legacy of choosing a NON-thyroid hormone level to define a THYROID hormone condition.

Our TSH did not cause the disease of hypothyroidism. TSH is a biochemical side effect of low T4. High TSH is a clear signal of low T4 … before we are treated with thyroid hormone.

Yet fixing our TSH is supposed to fix us? No, all it has done is put us in a TSH based category. Meanwhile, due to the artificial distortions of therapy, our thyroid hormones can continue to be low, especially our Free T3. Yes, even if TSH is normal.

Logic, folks. Basic logic. We don’t have a condition called “Hyper-thyrotropin-emia” (thyrotropin is another medical term for TSH). We are hypoTHYROID. Test. Thyroid. Hormones.

Even if we have perfectly optimized pharmaceutical support, our thyroid hormone metabolism is too rigidly controlled by medication, an artificial and static daily dose, not a living, adjusting gland. Therefore, we cannot adapt as easily to things that will inevitably cause thyroid hormone shifts — such as cold climate, pregnancy, menopause, and estrogen. To the degree that some still depend on partial thyroid gland function, we are also at the mercy of environmental toxins (endocrine disruptors) like fluoride that can interfere with thyroid hormone synthesis.

As for our lifelong disease progression, autoimmune thyroid disease does not stop progressing or shifting for the rest of our lives.

As I’ve said before, we may have had a thyroidectomy, but there’s no such thing as an antibody-ectomy.

Those of us with autoimmune hypothyroidism do continue to lose thyroid gland tissue over the course of our lives.

Thyroid antibody levels can flare no matter what our thyroid gland status is. Research has shown these antibodies can cause havoc far beyond the thyroid gland itself. In Hashimoto’s, antibody flares are associated with more severe symptoms throughout the body. In Graves’ disease, the antibodies can cause thyroid eye disease (TED, Graves’ ophthalmopathy) even after the thyroid gland is gone, and Graves’ disease antibodies can interfere with TSH secretion at the ultrashort feedback loop, causing incorrect management of therapy.

What else makes a chronic disease eligible to be on this list?

Does it have to be a crisis? We would be in crisis if they kept stats on its rising prevalence in Canada. Hypothyroidism rates are rising in other parts of the world that do keep stats.

Does it have a certain amount of people? We are just as numerous and possibly more numerous as many who have diseases on this list. At least 2-5% of the population, perhaps more, have overt hypothyroidism, again based on other countries’ stats. There are going to be a lot more if you include subclinical hypothyroidism (elevated TSH with normal T4), many of whom could be a long way down the road of autoimmune thyroid disease.

Is hypothyroidism not chronic enough or not disease-ish enough?

Boy do we have something to say on that matter. Myths to dispel. Does our condition not cause a reduction in quality of life and ability to function even when it is treated well?

Are some of us actually “disabled” by it, unable to work? Yes, absolutely.

Does it put our lives at risk? Um, yes. Look up myxedema coma.

Also, consider the medical tragedy of “non-thyroidal illness” or “low T3 syndrome.” As chronic hypothyroid people, we may not be able to recover from a car accident or massive burn injuries or kidney failure if our T3 drops low and all we’re given in hospital is T4. T4 hormone won’t convert to T3 sufficiently when the D3 enzyme is upregulated by organs in severe crisis. In the early phases of low T3 syndrome, the body lowers the metabolic rate by dumping T3. At a certain point, the loss of T3 becomes pathological and people do die from it. Low T3 is the strongest predictor of death in critical illness, not obesity, not smoking status, not diabetes status, not age. If we had a living thyroid gland that could be stimulated to produce T3, we could recover naturally. But we don’t. And it is mind-boggling but true that NObody has bothered to research how often we die from this incorrectly medicated state of risk of imminent death. We are excluded from 99% of studies of nonthryoidal illness because we take thyroid hormone and we are assumed to be ok, when all the science would say no, we are not.

Are there any downsides to having hypothyroidism listed here as a chronic disease?

Some unwanted side effects?

Yes, potentially. Here is a challenge of being on the list. A minor annoyance compared to what I’ve just outlined.

Chronic diseases are often seen as preventable with public health campaigns on lifestyle and diet.

This would be one undesirable side-effect of being included in a list side by side with Type 2 diabetes.

This is something that the Diabetes community likely continues to struggle with — the lack of public understanding of the distinction between type 1 and type 2.

Type 1 diabetes is, like permanent hypothyroidism, a disease that cannot be prevented or cured by diet and lifestyle alone.

Although diet and lifestyle interventions do affect both antibodies and hormone metabolism, and they can always help to tweak and minimize the harms of poor pharmaceutical treatment of hypothyroidism, diet and lifestyle interventions CANNOT cure dead or missing thyroid gland tissue. To believe otherwise is to be unscientific and believe in magic.

Correct pharmaceutical intervention, based on appropriate testing and ongoing medical education, is the foundation of our lifelong chronic disease management.

For thyroid therapy to advance, we do need the support of chronic disease status.

Advocacy on this front is something to seriously consider as we develop our campaign into a registered organization.

Canadian health policy has it wrong. YES, Hypothyroidism is a chronic disease, just as much as any of those listed. It is not cured. It’s poorly managed. Let’s do it better.

LINKS:

Canada: A-Z Chronic Diseases (list)
https://www.canada.ca/en/public-health/services/chronic-diseases/a-chronic-diseases.html

Canada: Chronic Diseases
https://www.canada.ca/en/public-health/services/chronic-diseases.html

Canada: Chronic Disease Data and Indicators (research, stats)
https://www.canada.ca/en/public-health/services/chronic-diseases/chronic-disease-facts-figures.html

SELECTED REFERENCES

In several sections

HYPOTHYROIDISM PREVALENCE

Garmendia Madariaga, A., Santos Palacios, S., Guillén-Grima, F., & Galofré, J. C. (2014). The Incidence and Prevalence of Thyroid Dysfunction in Europe: A Meta-Analysis. The Journal of Clinical Endocrinology & Metabolism, 99(3), 923–931. https://doi.org/10.1210/jc.2013-2409

Giorda, C. B., Carnà, P., Romeo, F., Costa, G., Tartaglino, B., & Gnavi, R. (2017). Prevalence, incidence and associated comorbidities of treated hypothyroidism: an update from a European population. European Journal of Endocrinology, 176(5), 533–542. https://doi.org/10.1530/EJE-16-0559

Lerner, A., Jeremias, P., & Matthias, T. (2015). The World Incidence and Prevalence of Autoimmune Diseases is Increasing. International Journal of Celiac Disease, International Journal of Celiac Disease, 3(4), 151–155. https://doi.org/10.12691/ijcd-3-4-8

DISABILITY AND QUALITY OF LIFE

Dow, K. H., Ferrell, B. R., & Anello, C. (1997). Quality-of-Life Changes in Patients with Thyroid Cancer After Withdrawal of Thyroid Hormone Therapy. Thyroid, 7(4), 613–619. https://doi.org/10.1089/thy.1997.7.613

Feller, M., Snel, M., Moutzouri, E., Bauer, D. C., de Montmollin, M., Aujesky, D., … Dekkers, O. M. (2018). Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis. JAMA, 320(13), 1349–1359. https://doi.org/10.1001/jama.2018.13770

Gussekloo, J., van Exel, E., de Craen, A. J. M., Meinders, A. E., Frölich, M., & Westendorp, R. G. J. (2004). Thyroid status, disability and cognitive function, and survival in old age. JAMA, 292(21), 2591–2599. https://doi.org/10.1001/jama.292.21.2591

Hoftijzer, C., Heemstra, A., Corssmit, P. M., Van Der Klaauw, A., Romijn, A., & Smit, W. A. (2008). Quality of Life in Cured Patients with Differentiated Thyroid Carcinoma. The Journal of Clinical Endocrinology & Metabolism, 93(1), 200–203. https://doi.org/10.1210/jc.2007-1203

Jaeschke, R., Guyatt, G., Cook, D., Harper, S., & Gerstein, H. C. (1994). Spectrum of quality of life impairment in hypothyroidism. Quality of Life Research: An International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation, 3(5), 323–327.

Michaelsson, L. F., la Cour, J. L., Medici, B. B., Watt, T., Faber, J., & Nygaard, B. (2018). Levothyroxine/Liothyronine Combination Therapy and Quality of Life: Is It All about Weight Loss? European Thyroid Journal, 7(4), 184–191. https://doi.org/10.1159/000490383

Nelson, R. (2018a, September 6). Symptoms of Hypothyroidism Affect Quality of Life Despite Levothyroxine Therapy. Retrieved November 10, 2018, from Endocrinology Advisor website: https://www.endocrinologyadvisor.com/thyroid/hypothyroidism-comorbidities-poor-qol-negative-impact-patients/article/793538/

Nexo, M. A., Watt, T., Feldt-Rasmussen, U., Rasmussen, A., Bonnema, S. J., Hegedus, L., … Bjorner, J. (2012). Does thyroid disease affect work function? Results from a qualitative study. Quality Of Life Research, 21, 112–112.

Nexo, M. A., Watt, T., Pedersen, J., Bonnema, S. J., Hegedüs, L., Rasmussen, A. K., … Bjorner, J. B. (2014). Increased risk of long-term sickness absence, lower rate of return to work, and higher risk of unemployment and disability pensioning for thyroid patients: a Danish register-based cohort study. The Journal of Clinical Endocrinology and Metabolism, 99(9), 3184–3192. https://doi.org/10.1210/jc.2013-4468

Nexo, Mette Andersen, Watt, T., Bonnema, S. J., Hegedüs, L., Rasmussen, Å. K., Feldt-Rasmussen, U., & Bjorner, J. B. (2015). Thyroid-specific questions on work ability showed known-groups validity among Danes with thyroid diseases. Quality of Life Research, 24(7), 1615–1627. https://doi.org/10.1007/s11136-014-0896-0

Pearce, S. H. S., Razvi, S., Yadegarfar, M. E., Martin-Ruiz, C., Kingston, A., Collerton, J., … Jagger, C. (2016). Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study. The Journal of Clinical Endocrinology and Metabolism, 101(11), 4385–4394. https://doi.org/10.1210/jc.2016-1935

THYROID THERAPY & CLIMATE, PREGNANCY, MENOPAUSE, ESTROGEN, FLUORIDE

Gullo, D., Latina, A., Frasca, F., Squatrito, S., Belfiore, A., & Vigneri, R. (2017). Seasonal variations in TSH serum levels in athyreotic patients under L-thyroxine replacement monotherapy. Clinical Endocrinology, 87(2), 207–215. https://doi.org/10.1111/cen.13351

Han, Y., Mao, L.-J., Ge, X., Huang, K., Yan, S.-Q., Ren, L.-L., … Tao, F.-B. (2018). Thyroid autoantibodies in pregnancy are associated with hypertensive disorders of pregnancy: Ma’anshan Birth Cohort Study. Clinical Endocrinology, 88(6), 928–935. https://doi.org/10.1111/cen.13590

Karakosta, P., Alegakis, D., Georgiou, V., Roumeliotaki, T., Fthenou, E., Vassilaki, M., … Chatzi, L. (2012). Thyroid Dysfunction and Autoantibodies in Early Pregnancy Are Associated with Increased Risk of Gestational Diabetes and Adverse Birth Outcomes. The Journal of Clinical Endocrinology & Metabolism, 97(12), 4464–4472. https://doi.org/10.1210/jc.2012-2540

Li, Jia, Shen, J., & Qin, L. (2017). Effects of Levothyroxine on Pregnancy Outcomes in Women With Thyroid Dysfunction: A Meta-analysis of Randomized Controlled Trials. Alternative Therapies in Health and Medicine, 23(2), 49–58.

Nazarpour, S., Tehrani, F. R., Simbar, M., Tohidi, M., Majd, H. A., & Azizi, F. (2017). Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with autoimmune thyroid disease. European Journal of Endocrinology, 176(2), 253–265. https://doi.org/10.1530/EJE-16-0548

Resetkova, E., Notenboom, R., Arreaza, G., Mukuta, T., Yoshikawa, N., & Volpé, R. (1994). Seroreactivity to Bacterial Antigens Is Not a Unique Phenomenon in Patients with Autoimmune Thyroid Diseases in Canada. Thyroid, 4(3), 269–274. https://doi.org/10.1089/thy.1994.4.269

Schoutens, A., Laurent, E., Markowicz, E., & Lisart, J. (1991). Serum triiodothyronine, bone turnover, and bone mass changes in euthyroid pre- and postmenopausal women. Calcified Tissue International, 49(2), 95.

Franklyn, J. a., Betteridge, J., Holder, R., & Sheppard, M. c. (1995). Effect of Estrogen Replacement Therapy upon Bone Mineral Density in Thyroxine-Treated Postmenopausal Women with a Past History of Thyrotoxicosis. Thyroid, 5(5), 359–363. https://doi.org/10.1089/thy.1995.5.359

Utiger, Robert D. (n.d.). Estrogen, Thyroxine Binding in Serum, and Thyroxine Therapy | NEJM. Retrieved June 30, 2018, from New England Journal of Medicine website: https://www-nejm-org.ezproxy.lib.ucalgary.ca/doi/full/10.1056/NEJM200106073442310

Barberio, A. M., Hosein, F. S., Quiñonez, C., & McLaren, L. (2017). Fluoride exposure and indicators of thyroid functioning in the Canadian population: implications for community water fluoridation. J Epidemiol Community Health, 71(10), 1019–1025. https://doi.org/10.1136/jech-2017-209129

Chaitanya, N. C. S. K., Karunakar, P., Allam, N. S. J., Priya, M. H., Alekhya, B., & Nauseen, S. (2018). A systematic analysis on possibility of water fluoridation causing hypothyroidism. Indian Journal of Dental Research: Official Publication of Indian Society for Dental Research, 29(3), 358–363. https://doi.org/10.4103/ijdr.IJDR_505_16

Peckham, S., Lowery, D., & Spencer, S. (2017). Fluoride levels in drinking water and hypothyroidism: Response to Grimes and Newton et al. J Epidemiol Community Health, 71(4), 313–314. https://doi.org/10.1136/jech-2016-208632

CHRONIC EFFECTS OF THYROID ANTIBODIES

Al-Juburi, S., Taresh, H. R., Mahmood, A. A., & Al-Fatlawi, R. B. M. (2015). The Relationship Between Anti-Thyroidal Peroxidise Antibodies and Thyroid Hormones (T3, T4 And Thyroid Stimulating Hormone TSH) Among Patients With Autoimmune Thyroid Disease. European Scientific Journal.

Amouzegar, A., Gharibzadeh, S., Kazemian, E., Mehran, L., Tohidi, M., & Azizi, F. (2017). The Prevalence, Incidence and Natural Course of Positive Antithyroperoxidase Antibodies in a Population-Based Study: Tehran Thyroid Study. PLOS ONE, 12(1), e0169283. https://doi.org/10.1371/journal.pone.0169283

Ando, T., Latif, R., & Davies, TerryF. (2005). Thyrotropin receptor antibodies: new insights into their actions and clinical relevance. Best Practice & Research Clinical Endocrinology & Metabolism, 19(1), 33–52. https://doi.org/10.1016/j.beem.2004.11.005

Awad, S., Dutton, H., Shaw, J., & Keely, E. (2017). Pregnancy and autoimmune thyroid disease: alternating between hypothyroidism and hyperthyroidism and the role of thyrotropin-receptor antibodies. AACE Clinical Case Reports, 3(4), e340–e343. https://doi.org/10.4158/EP161660.CR

Barić, Ana, Brčić, L., Gračan, S., Škrabić, V., Brekalo, M., Šimunac, M., … Boraska Perica, V. (2018). Thyroglobulin Antibodies are Associated with Symptom Burden in Patients with Hashimoto’s Thyroiditis: A Cross-Sectional Study. Immunological Investigations, 1–12. https://doi.org/10.1080/08820139.2018.1529040

Blanchin, S., Coffin, C., Viader, F., & Ruf, J. (2007). Anti-thyroperoxidase antibodies from patients with Hashimoto’s encephalopathy bind to cerebellar astrocytes. Journal of Neuroimmunology, 192(1), 13–20. https://doi.org/10.1016/j.jneuroim.2007.08.012

Bocchetta, A., Traccis, F., Mosca, E., Serra, A., Tamburini, G., & Loviselli, A. (2016). Bipolar disorder and antithyroid antibodies: review and case series. International Journal of Bipolar Disorders, 4. https://doi.org/10.1186/s40345-016-0046-4

Brokken, J. S., Wiersinga, M., & Prummel, F. (2003). Thyrotropin Receptor Autoantibodies Are Associated with Continued Thyrotropin Suppression in Treated Euthyroid Graves’ Disease Patients. The Journal of Clinical Endocrinology & Metabolism, 88(9), 4135–4138. https://doi.org/10.1210/jc.2003-030430

Bunevicius, R., Velickiene, D., & Prange, A. J. (2005). Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves’ disease. General Hospital Psychiatry, 27(2), 133–139. https://doi.org/10.1016/j.genhosppsych.2004.10.002

Chung, Y. J., Lee, B. W., Kim, J.-Y., Jung, J. H., Min, Y.-K., Lee, M.-S., … Chung, J. H. (2006). Continued suppression of serum TSH level may be attributed to TSH receptor antibody activity as well as the severity of thyrotoxicosis and the time to recovery of thyroid hormone in treated euthyroid Graves’ patients. Thyroid: Official Journal of the American Thyroid Association, 16(12), 1251–1257. https://doi.org/10.1089/thy.2006.16.1251

Han, Y., Mao, L.-J., Ge, X., Huang, K., Yan, S.-Q., Ren, L.-L., … Tao, F.-B. (2018). Thyroid autoantibodies in pregnancy are associated with hypertensive disorders of pregnancy: Ma’anshan Birth Cohort Study. Clinical Endocrinology, 88(6), 928–935. https://doi.org/10.1111/cen.13590

Khoo, D. H., Eng, P. H., Ho, S. C., Tai, E. S., Morgenthaler, N. G., Seah, L. L., … Aw, S. E. (2000). Graves’ ophthalmopathy in the absence of elevated free thyroxine and triiodothyronine levels: prevalence, natural history, and thyrotropin receptor antibody levels. Thyroid: Official Journal of the American Thyroid Association, 10(12), 1093–1100. https://doi.org/10.1089/thy.2000.10.1093

Polovina, S. P., Miljic, D., Zivojinovic, S., Milic, N., Micic, D., & Popovic Brkic, V. (2017). The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women. Hormones (Athens, Greece), 16(1), 54–61. https://doi.org/10.14310/horm.2002.1719

HYPOTHYROIDISM AND OTHER CHRONIC DISEASES

Ascheim, D. D., & Hryniewicz, K. (2002). Thyroid Hormone Metabolism in Patients with Congestive Heart Failure: The Low Triiodothyronine State. Thyroid, 12(6), 511–515. https://doi.org/10.1089/105072502760143908

Boutzios, G., Alexandraki, K., Liatis, S., Makrilakis, K., Lampropoulou, E., Nikolopoulos, G., … Kaltsas, G. (2015). The prevalence of pre-diabetes, insulin sensitivity indices and glucose levels are increased in patients with autoimmune thyroiditis. Diabetologia, 58, S301.

Demartini, B., Masu, A., Scarone, S., Pontiroli, A. E., & Gambini, O. (2010). Prevalence of depression in patients affected by subclinical hypothyroidism. Panminerva Medica, 52(4), 277–282.

Farasat, T., Cheema, A. M., & Khan, M. N. (2012). Hyperinsulinemia and insulin resistance is associated with low T3/T4 ratio in pre diabetic euthyroid pakistani subjects. Journal of Diabetes and Its Complications, 26(6), 522. https://doi.org/10.1016/j.jdiacomp.2012.05.017

Fontana, M., Passino, C., Poletti, R., Zyw, L., Prontera, C., Scarlattini, M., … Iervasi, G. (2012). Low triiodothyronine and exercise capacity in heart failure. International Journal of Cardiology, 154(2), 153–157. https://doi.org/10.1016/j.ijcard.2010.09.002

Fontenelle, L. C., Feitosa, M. M., Severo, J. S., Freitas, T. E. C., Morais, J. B. S., Torres-Leal, F. L., … Marreiro, D. do N. (2016). Thyroid Function in Human Obesity: Underlying Mechanisms. Hormone and Metabolic Research, 48(12), 787–794. https://doi.org/10.1055/s-0042-121421

Gerdes, A. (2011). Low Thyroid function and myocardial infarction. Grantome – National Institutes of Health. Retrieved from http://grantome.com/grant/NIH/R01-HL103671-01A1

Iglesias, Pedro, Bajo, M. A., Selgas, R., & Díez, J. J. (2017). Thyroid dysfunction and kidney disease: An update. Reviews in Endocrine and Metabolic Disorders, 18(1), 131–144. https://doi.org/10.1007/s11154-016-9395-7

Kabadi, U. M., & Premachandra, B. N. (1984). Low triiodothyronine and raised reverse triiodothyronine levels in patients over fifty years of age who have type II diabetes mellitus: influence of metabolic control, not age. Journal of the American Geriatrics Society, 32(5), 375–379.

Karimi, F., Haghighi, A. B., & Petramfar, P. (2011). Low Levels of Triiodothyronine in Patients with Alzheimer’s Disease. Iranian Journal of Medical Sciences, 36(4), 322–323. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470275/

Kaya, H., Ertas, F., & Soydinc, M. S. (2012). Low serum free triiodothyronine levels are associated with the presence and severity of coronary artery disease in the euthyroid patients: an observational study. The Anatolian Journal of Cardiology (Anadolu Kardiyoloji Dergisi), 12(7), 591.

Quinlan, P., Horvath, A., Wallin, A., & Svensson, J. (2019). Low serum concentration of free triiodothyronine (FT3) is associated with increased risk of Alzheimer’s disease. Psychoneuroendocrinology, 99, 112–119. https://doi.org/10.1016/j.psyneuen.2018.09.002

Quinlan, P., Nordlund, A., Lind, K., Gustafson, D., Edman, Å., & Wallin, A. (2010). Thyroid Hormones Are Associated with Poorer Cognition in Mild Cognitive Impairment. Dementia and Geriatric Cognitive Disorders, 30(3), 205–211. https://doi.org/10.1159/000319746

Rhee, C. M., Alexander, E. K., Bhan, I., & Brunelli, S. M. (2013). Hypothyroidism and mortality among dialysis patients. Clinical Journal of the American Society of Nephrology: CJASN, 8(4), 593–601. https://doi.org/10.2215/CJN.06920712

Rhee, C. M. (2016). The Interaction Between Thyroid and Kidney Disease: An Overview of the Evidence. Current Opinion in Endocrinology, Diabetes, and Obesity, 23(5), 407–415. https://doi.org/10.1097/MED.0000000000000275

Sato, Y., Yoshihisa, A., Kimishima, Y., Kiko, T., Kanno, Y., Yokokawa, T., … Takeishi, Y. (2019). Low T3 Syndrome Is Associated With High Mortality in Hospitalized Patients With Heart Failure. Journal of Cardiac Failure, 25(3), 195–203. https://doi.org/10.1016/j.cardfail.2019.01.007

Sato, Y., Yoshihisa, A., Kimishima, Y., Kiko, T., Watanabe, S., Kanno, Y., … Takeishi, Y. (2018). Subclinical Hypothyroidism Is Associated With Adverse Prognosis in Heart Failure Patients. Canadian Journal of Cardiology, 34(1), 80–87. https://doi.org/10.1016/j.cjca.2017.10.021

Song, S. H., Kwak, I. S., Lee, D. W., Kang, Y. H., Seong, E. Y., & Park, J. S. (2009). The prevalence of low triiodothyronine according to the stage of chronic kidney disease in subjects with a normal thyroid-stimulating hormone. Nephrology Dialysis Transplantation, 24(5), 1534–1538. https://doi.org/10.1093/ndt/gfn682

Taddei, S., Caraccio, N., Virdis, A., Dardano, A., Versari, D., Ghiadoni, L., … Monzani, F. (2006). Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto’s thyroiditis. The Journal of Clinical Endocrinology and Metabolism, 91(12), 5076–5082. https://doi.org/10.1210/jc.2006-1075

Tang, Y.-D., Kuzman, J. A., Said, S., Anderson, B. E., Wang, X., & Gerdes, A. M. (2005). Low Thyroid Function Leads to Cardiac Atrophy With Chamber Dilatation, Impaired Myocardial Blood Flow, Loss of Arterioles, and Severe Systolic Dysfunction. Circulation, 112(20), 3122–3130. https://doi.org/10.1161/CIRCULATIONAHA.105.572883

Wang, C.-Y., Yu, T.-Y., Shih, S.-R., Huang, K.-C., & Chang, T.-C. (2018). Low total and free triiodothyronine levels are associated with insulin resistance in non-diabetic individuals. Scientific Reports, 8. https://doi.org/10.1038/s41598-018-29087-1

Weltman, N. Y., Ojamaa, K., Schlenker, E. H., & Chen, Y.-F. (2014). Low-dose T₃ replacement restores depressed cardiac T₃ levels, preserves coronary microvasculature and attenuates cardiac dysfunction in experimental diabetes mellitus. Molecular Medicine (Cambridge, Mass.), 20, 302.

LOW T3 SYNDROME / NON-THYROIDAL ILLNESS

Ataoğlu, H. E., Ahbab, S., Serez, M. K., Yamak, M., Kayaş, D., Canbaz, E. T., … Yenigün, M. (2018a). Prognostic significance of high free T4 and low free T3 levels in non-thyroidal illness syndrome. European Journal of Internal Medicine, 57, 91–95. https://doi.org/10.1016/j.ejim.2018.07.018

Bertoli, A., Valentini, A., Cianfarani, M. A., Gasbarra, E., Tarantino, U., & Federici, M. (2017). Low FT3: a possible marker of frailty in the elderly. Clinical Interventions in Aging, 12, 335–341. https://doi.org/10.2147/CIA.S125934

Brent, G. A., & Hershman, J. M. (1986). Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. The Journal of Clinical Endocrinology and Metabolism, 63(1), 1–8. https://doi.org/10.1210/jcem-63-1-1

  • Quote from abstract: “T4 therapy was not beneficial in this population of intensive care unit patients, and by inhibiting TSH secretion, it may suppress an important mechanism for normalization of thyroid function during recovery.”

Bunevicius, A., Iervasi, G., & Bunevicius, R. (2015). Neuroprotective actions of thyroid hormones and low-T3 syndrome as a biomarker in acute cerebrovascular disorders. Expert Review of Neurotherapeutics, 15(3), 315–326. https://doi.org/10.1586/14737175.2015.1013465

Bunevičius, R. (2009). Low Triiodothyronine Syndrome and Depression in Patients with Chronic Heart Failure. In G. Iervasi & A. Pingitore (Eds.), Thyroid and Heart Failure (pp. 203–212). Retrieved from http://www.springerlink.com/index/10.1007/978-88-470-1143-4_18

Cerillo, A. G., Storti, S., Kallushi, E., & Haxhiademi, D. (2014). The low triiodothyronine syndrome: a strong predictor of low cardiac output and death in patients undergoing coronary artery bypass grafting. The Annals of Thoracic Surgery, 97(6), 2089.

Fragidis, S., Sombolos, K., Thodis, E., Panagoutsos, S., Mourvati, E., Pikilidou, M., … Vargemezis, V. (2015). Low T3 syndrome and long-term mortality in chronic hemodialysis patients. World Journal of Nephrology, 4(3), 415–422. https://doi.org/10.5527/wjn.v4.i3.415

Gangemi, E. N., Garino, F., Berchialla, P., & Martinese, M. (2008). Low triiodothyronine serum levels as a predictor of poor prognosis in burn patients. Burns, 34(6), 817–824. https://doi.org/10.1016/j.burns.2007.10.002

Gao, R., Chen, R.-Z., Xia, Y., Liang, J.-H., Wang, L., Zhu, H.-Y., … Xu, W. (2018). Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia. International Journal of Cancer, 143(3), 466–477. https://doi.org/10.1002/ijc.31327

Gao, R., Liang, J.-H., Wang, L., Zhu, H.-Y., Wu, W., Wu, J.-Z., … Xu, W. (2017). Low T3 syndrome is a strong prognostic predictor in diffuse large B cell lymphoma. British Journal of Haematology, 177(1), 95–105. https://doi.org/10.1111/bjh.14528

Horácek, J., Sulková, S. D., Kubisová, M., & Safránek, R. (2012). Thyroid Hormone Abnormalities in Hemodialyzed Patients: Low Triiodothyronine As Well As High Reverse Triiodothyronine Are Associated With Increased Mortality. Physiological Research, 61(5), 495.

Iervasi, G., Pingitore, A., Landi, P., & Raciti, M. (2003). Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation, 107(5), 708.

Iglesias, P., Muñoz, A., Prado, F., Guerrero, M. T., Macías, M. C., Ridruejo, E., … Díez, J. J. (2010). Serum thyrotropin concentration is an early marker of normalization of low triiodothyronine syndrome in aged hospitalized patients after discharge. Journal of Endocrinological Investigation, 33(9), 607–611. https://doi.org/10.1007/BF03346657

Katzeff, H. L., Powell, S. R., & Ojamaa, K. (1997). Alterations in cardiac contractility and gene expression during low-T3 syndrome: prevention with T3. The American Journal of Physiology, 273(5 Pt 1), E951-956.

Kohno, A., & Hara, Y. (2001). Severe Myocardial lschemia following Hormone Replacement in Two Cases of Hypothyroidism with Normal Coronary Arteriogram. Endocrine Journal, 48(5), 565–572. Retrieved from https://www.jstage.jst.go.jp/article/endocrj1993/48/5/48_5_565/_pdf

  • Abstract is worth quoting:  Two cases of hypothyroidism with cardiac attack (acute myocardial infarction, AMI) following thyroxine [T4] replacement were reported. Neither of these cases showed any major coronary artery disease. The first case was a 58 year-old male who was treated with L-thyroxine (initial dose 0.025 mg/day) for hypothyroidism due to Hashimoto’s disease. The dose was increased up to 0.1 mg/day within 2 weeks. Acute myocardial infarction occurred 6 weeks after the replacement was started. Angiographical study showed no notable pathological change in major coronary arteries, but echocardiography demonstrated diffuse hypokinesis of the left ventricular wall. The second case was a 61-year-old female who suffered from Graves’ disease and had been treated with thiamazole (2.5 mg/day) for 15 years. Later, she became hypothyroid and was treated with thyroxine. At first, 0.05 mg/day of L-thyroxine was given, and then the dose was increased up to 0.1 mg/day after the 7th week. Acute myocardial infarction occurred 3 weeks after the dose was increased. Angiographic study of the coronary arteries revealed no abnormality. Possible causes of AMI in thyroxine replacement were discussed in relation to vascular spasm and small vessel disease of the heart. Importance of echocardiographic study before hormone replacement therapy is stressed, particularly for middle/old-aged patients with long-term hypothyroidism.

Kumar, K. V. S. H., Kapoor, U., Kalia, R., Chandra, N. S. A., Singh, P., & Nangia, R. (2013). Low triiodothyronine predicts mortality in critically ill patients. Indian Journal of Endocrinology and Metabolism, 17(2), 285–288. https://doi.org/10.4103/2230-8210.109715

Lee, Y.-M., Ki, Y.-J., Choi, D.-H., & Kim, B.-B. (2015). Value of Low Triiodothyronine and Subclinical Myocardial Injury for Clinical Outcomes in Chest Pain. The American Journal of the Medical Sciences, 350(5), 393.

Lin, C., Lin, K., Guo, Y., You, Z., Zheng, W., Lin, F., … Zhu, P. (2019). Low free triiodothyronine is associated with contrast-induced acute kidney injury and long-term outcome in elderly patients who underwent percutaneous coronary intervention. Anatolian Journal of Cardiology, 21(2), 60–67. https://doi.org/10.14744/AnatolJCardiol.2018.38228

Liu, Jinliang, Wu, X., Lu, F., Zhao, L., Shi, L., & Xu, F. (2016). Low T3 syndrome is a strong predictor of poor outcomes in patients with community-acquired pneumonia. Scientific Reports, 6. https://doi.org/10.1038/srep22271

Meyer, S., Schuetz, P., Wieland, M., & Nusbaumer, C. (2011). Low triiodothyronine syndrome: a prognostic marker for outcome in sepsis? Endocrine, 39(2), 167–174. https://doi.org/10.1007/s12020-010-9431-4

Pingitore, A., Galli, E., Barison, A., & Iervasi, A. (2008). Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. The Journal of Clinical Endocrinology and Metabolism, 93(4), 1351.

Pingitore, A., Landi, P., Taddei, M. C., & Ripoli, A. (2005). Triiodothyronine levels for risk stratification of patients with chronic heart failure. The American Journal of Medicine, 118(2), 132–136. https://doi.org/10.1016/j.amjmed.2004.07.052

Preoperative low tri-iodothyronine concentration is associated with worse health status and shorter five year survival of primary brain tumor patients – Semantic Scholar. (n.d.). Retrieved June 12, 2018, from /paper/Preoperative-low-tri-iodothyronine-concentration-is-Bunevicius-Deltuva/49b81aa04281dbebcb6e1497581b91352da0eb89

Qiu, M., Fang, M., & Liu, X. (2017). Low free triiodothyronine levels predict symptomatic intracranial hemorrhage and worse short-term outcome of thrombolysis in patients with acute ischemia stroke. Medicine, 96(45). https://doi.org/10.1097/MD.0000000000008539

Rhee, C. M., Brent, G. A., Kovesdy, C. P., Soldin, O. P., Nguyen, D., Budoff, M. J., … Kalantar-Zadeh, K. (2015). Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients. Nephrology Dialysis Transplantation, 30(5), 724–737. https://doi.org/10.1093/ndt/gfu024

Ruiz-Núñez, B., Tarasse, R., Vogelaar, E. F., Dijck-Brouwer, J., A, D., & Muskiet, F. A. J. (2018). Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study. Frontiers in Endocrinology, 9. https://doi.org/10.3389/fendo.2018.00097

Sato, Y., Yoshihisa, A., Kimishima, Y., Kiko, T., Kanno, Y., Yokokawa, T., … Takeishi, Y. (2019). Low T3 Syndrome Is Associated With High Mortality in Hospitalized Patients With Heart Failure. Journal of Cardiac Failure, 25(3), 195–203. https://doi.org/10.1016/j.cardfail.2019.01.007

Su, Wen, Zhao, X.-Q., Wang, M., Chen, H., & Li, H.-W. (2018). Low T3 syndrome improves risk prediction of in-hospital cardiovascular death in patients with acute myocardial infarction. Journal of Cardiology, 72(3), 215–219. https://doi.org/10.1016/j.jjcc.2018.02.013

Suda, S., Shimoyama, T., Nagai, K., Arakawa, M., Aoki, J., Kanamaru, T., … Kimura, K. (2018). Low Free Triiodothyronine Predicts 3-Month Poor Outcome After Acute Stroke. Journal of Stroke and Cerebrovascular Diseases: The Official Journal of National Stroke Association, 27(10), 2804–2809. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.06.009

Yazıcı, S., Kırış, T., Ceylan, U. S., Terzi, S., Erdem, A., Atasoy, I., … Yeşilçimen, K. (2017a). Relation of Low T3 to One-Year Mortality in Non-ST-Elevation Acute Coronary Syndrome Patients. Journal of Clinical Laboratory Analysis, 31(2). https://doi.org/10.1002/jcla.22036

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