CBC opinion article draft on subclinical hypothyroidism and its therapy

Subclinical-Further-beyond-reach-CBCI just sent this opinion article draft to the CBC opinion editors by email.

Dear CBC opinion editors,
I would like to offer my opinion piece on this trending topic.

First, about me, then the article draft:

I am the main researcher and writer for the Canadian Thyroid Patients’ Campaign, who launched a federal petition in 2018 that was sponsored and read in parliament in early January 2019. You can find out more about our fledgling organization and about me, its writer, on our website at thyroidpatients.ca .

In my day job, I serve as an associate professor of communication at the University of Calgary. I research thyroid mainly as a patient-advocate and secondarily as a scholar of rhetoric who analyzes the argumentation (logic, reasoning) and the ethics of thyroid science and policy (thyroid therapy guidelines). I am not a biological scientist or health professional. My research in thyroid is as an avid reader of thyroid scientific literature published in journals and medical textbooks.

I am pitching the following article to you.

DRAFT

TITLE 1: The gray area of subclinical hypothyroidism
TITLE 2: Why levothyroxine does not work for everyone
TITLE 3: Diagnosing hypothyroidism is more complex than just testing TSH and T4
TITLE 4: Understanding subclinical hypothyroidism and its therapy

The recent guidelines on “subclinical hypothyroidism” published in the British Medical Journal (May 2019) are generating more heat than light. It made sweeping generalizations about “thyroid hormones” not having any clinical benefit, when that is not true for everyone with a diagnosis of “subclinical hypothyroidism.”

Two major factors complicate the issue: our system of diagnosis is not working well, and our therapeutic approach is not working well.

This gray area of diagnosis and treatment has been debated and studied in thyroid science for decades. Ever since the rise of the TSH test and the rise of levothyroxine therapy, which went hand in hand in the 1970s through 1990s, people have investigated the borderline condition of “subclinical” hypothyroidism and its health risks, and whether or not levothyroxine therapy removes those health risks.

In some areas of thyroid therapy there is absolute certainty: People whose thyroid glands no longer function well enough, or people who have had a thyroid gland removed, do require thyroid hormone replacement.

We require thyroid hormone for all our body’s cells and tissues to function. It is not just a problem localized to a gland in the throat or our metabolic rate. For too long, society has conceived of hypothyroidism as a lazy thyroid gland that just needs a little prodding to get going again.

Popular discourse often associates the hypothyroid state with common symptoms every human being can experience during life: fatigue, cognitive difficulty, hair loss, cold sensitivity, and weight gain. Conceiving of it this way can minimize the health condition and dismiss those who truly suffer a thyroid hormone deficiency as whining people who just need to exercise more, eat healthy food, and get a therapist.

If we don’t treat genuine thyroid deficiency properly, there is no doubt that it will put a huge burden on our taxpayer-funded health care system. This should put the controversy about “subclinical” hypothyroidism into proper perspective next to that of a chronic state of permanent thyroid gland loss.

Loss of thyroid gland function can cause and/or worsen mental health problems, diabetes, obesity, heart failure and cardiovascular diseases. Serious thyroid hormone imbalances can cause infertility, miscarriage, fetal brain damage, and stunted growth. If you are severely hypothyroid and stop taking your medication, you can eventually end up in a life-threatening medical emergency called “myxedema coma.”

A “subclinical” diagnosis is a huge gray area in which TSH test results are mildly elevated above reference range while T4 thyroid hormone test results are in the statistically normal range, not yet below range.

In the “subclinical” diangosis gray zone, a doctor can’t tell if a person’s thyroid gland is working well or not.

Within that gray area are two types of people, those who are not hypothyroid and those who are and may require appropriate thyroid therapy.

A huge percentage of people are not truly hypothyroid at all but are experiencing extra thyroid gland stimulation and temporarily reduced T4 production. The lab test results are just a snapshot of the TSH-T4 relationship, which is biologically designed to be a system in flux. In many cases, people have a T4 level that is just temporarily low, but it will soon rise under the influence of TSH stimulation. The body always needs to resupply lost thyroid hormone while recovering from a critical illness or fasting: this is known as the recovery phase of “non-thyroidal illness” or “low T3 syndrome.” Sometimes the TSH stimulation may continue for months if the body is under a form of stress that requires more thyroid hormone production, such as obesity or cold winter climate. A person with a chronically high TSH but effective T4 and T3 production is said to have an altered thyroid “set point.”

On the other hand, some people in this category are mildly hypothyroid with a chronically low-range T4. In this category are some people on their way to thyroid gland failure, most often due to autoimmune thyroid disease (Hashimoto’s thyroiditis), but in some, a thyroid failing due to age.

In this second category of thyroid-failing people, you have two subcategories: people with a healthy T3 hormone supply who are not symptomatic, and people who do not have enough T3 for their individual body and are therefore genuinely suffering “tissue hypothyroidism.”

On the way to thyroid gland failure, the human body does everything it can do to defend its T3 levels in blood (see Abdalla & Bianco, “Defending Plasma T3 is a Biological Priority.”). In thyroid-failing people, the extra TSH stimulation is a natural compensation for the loss of T4 production capacity.

By means of what scientists call a “TSH-T3 shunt,” blood containing TSH molecules stimulate the thyroid gland to not only increase the ratio of T3 to T4 hormone production, but also to convert T4 into T3 by strengthening “deiodinase” enzymes that remove a specific iodine atom from T4 to yield T3.

Within the broad statistical reference ranges for TSH, T4 and T3 are narrower individual set points or ranges for health, as discovered by Andersen and his team in 2002 and 2003.

An individual person’s healthy set point for each of these thyroid and pituitary hormones is half as wide as the statistical reference range.

When or if “thyroid-failing” people experience a loss in T3 hormone production and/or conversion that lowers their T3 below their healthy “set point,” they will be truly hypothyroid in their bodily tissues, even if T4 and T3 are still within in the normal population range, because their T3, the most essential hormone, is below its healthy set-point.

A diagnostic application called SPINA-Thyr aids in discerning people who are truly hypothyroid or on their way to thyroid gland failure. This tool has been developed by a team of endocrinologists led by Johannes Dietrich in Germany, who have refined the complex mathematical models of thyroid hormone production and conversion.

SPINA-Thyr has been clinically tested since 1999 and is freely downloadable. A clinician simply inputs the laboratory test results, units, and reference ranges for Free T3, Free T4, and TSH, and it will tell you how well the patient’s pituitary and thyroid glands are functioning and how efficiently the patient’s body is converting T4 into T3 hormone. Testing a patient over time and analyzing results through this application can show trends and aid in prognosis and therapy adjustments.

Why does levothyroxine fail some people? Because we do not all metabolize T4 to T3 at the same rate. Some of us have genetic problems with our deiodinase enzymes that become pathological in a thyroid-less state. When little or no thyroid tissue exists in these people, they are not able to resupply T3 by means of the TSH-T3 shunt, and their metabolism can’t make up the difference.

The news reports should not cause us to dismiss thyroid hormone testing and therapy. Instead, the problems with subclinical hypothyroidism and the relative ineffectiveness of levothyroxine for many people should be an opportunity for research.

Together, scientists must look past the limitations of the TSH-T4 paradigm and begin to understand the importance of T3 hormone, the complexities of thyroid hormone metabolism, and the individuality of each patient.

Tania S. Smith
22 Tuscany Valley Hts, NW
Calgary, Alberta

REFERENCES

Abdalla, S. M., & Bianco, A. C. (2014). Defending plasma T3 is a biological priority. Clinical Endocrinology, 81(5), 633–641. https://doi.org/10.1111/cen.12538

BBC. (2019, May 15). Thyroid disease “being over-treated.” Retrieved from https://www.bbc.com/news/health-48265023

Bekkering, G. E., Agoritsas, T., Lytvyn, L., Heen, A. F., Feller, M., Moutzouri, E., … Vermandere, M. (2019). Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ, 365, l2006. https://doi.org/10.1136/bmj.l2006

Berberich, J., Dietrich, J. W., Hoermann, R., & Müller, M. A. (2018). Mathematical Modeling of the Pituitary–Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis. Frontiers in Endocrinology, 9. https://doi.org/10.3389/fendo.2018.00091

Chatzitomaris, A., Hoermann, R., Midgley, J. E., Hering, S., Urban, A., Dietrich, B., … Dietrich, J. W. (2017). Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00163

Dietrich, J., Fischer, M., Jauch, J., Pantke, E., Gärtner, R., & Pickardt, C. (1999). SPINA-THYR: A novel systems theoretic approach to determine the secretion capacity of the thyroid gland. EFIM-2, 10(5 (Suppl 1)), S34.

Dietrich, J. W., Landgrafe-Mende, G., Wiora, E., Chatzitomaris, A., Klein, H. H., Midgley, J. E. M., & Hoermann, R. (2016). Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Frontiers in Endocrinology, 7. https://doi.org/10.3389/fendo.2016.00057

Economidou, F., Douka, E., Tzanela, M., Nanas, S., & Kotanidou, A. (2011). Thyroid function during critical illness. Hormones (Athens, Greece), 10(2), 117–124. https://doi.org/10.14310/horm.2002.1301

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

Janssen, R., Muller, A., & Simonides, W. S. (2017). Cardiac Thyroid Hormone Metabolism and Heart Failure. European Thyroid Journal, 6(3), 130–137. https://doi.org/10.1159/000469708

Hassi, J., Sikkilä, K., Ruokonen, A., & Leppäluoto, J. (2001). The pituitary-thyroid axis in healthy men living under subarctic climatological conditions. The Journal of Endocrinology, 169(1), 195–203.

Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2017). Recent advances in thyroid hormone regulation: Toward a new paradigm for optimal diagnosis and treatment. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00364

Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2015). Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, 47(9), 674–680. https://doi.org/10.1055/s-0034-1398616

Kishi, T. (2015). Free triiodothyronine, not thyroid stimulating hormone, should be focused on for risk stratification in acute decompensated heart failure. Journal of Cardiology, 66(3), 201–202. https://doi.org/10.1016/j.jjcc.2015.05.001

Mallipedhi, A., Vali, H., & Okosieme, O. (2011). Myxedema coma in a patient with subclinical hypothyroidism. Thyroid: Official Journal of the American Thyroid Association, 21(1), 87–89. LINK: https://www.ncbi.nlm.nih.gov/pubmed/21058937

Meier, C., Trittibach, P., Guglielmetti, M., Staub, J.-J., & Müller, B. (2003). Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism in patients with overt primary thyroid failure: cross sectional survey. BMJ, 326(7384), 311–312. https://doi.org/10.1136/bmj.326.7384.311

Nam, J. S., Cho, M., Park, J. S., & Ahn, C. W. (2010). Triiodothyronine level predicts visceral obesity and atherosclerosis in euthyroid, overweight and obese subjects: T3 and visceral obesity. Obesity Research & Clinical Practice, 4(4), e315–e323. https://doi.org/10.1016/j.orcp.2010.08.003

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.

Leave a Reply

Please log in using one of these methods to post your comment:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s