Subclinical hypothyroidism guidelines delay (in)effective therapy

Subclinical-Further-beyond-reachThis week, a BBC news article is circulating with the report that “Thyroid disease [is] being over-treated.” (May 15, 2019). (1)

More specifically, it reported that newly published guidelines claim that “almost all adults with mild or “subclinical” hypothyroidism will not benefit from hormone treatment.”

In response, thyroid-treated persons who suffer poorly optimized thyroid hormone levels are feeling even more depressed and grumpy about their disability than they normally do.

AN UNREACHABLE DIAGNOSIS

This newly published guideline by Bekkering and team (3) is based on a 2018 research review article by Feller and team, who analyzed 21 previous studies of subclinical hypothyroidism. (4).

Bekkering and colleages aim their attack “against thyroid hormones” in adults with Subclinical Hypothyroidism:

“The guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels).

It does not apply to

  1. women who are trying to become pregnant or
  2. patients with TSH >20 mIU/L.

It may not apply to

  1. patients with severe symptoms or
  2. young adults (such as those ≤30 years old).” (3)

We know what this means. Our modern medical systems are excessively focused on numbers, not careful reading, so it will be misinterpreted even more strictly than it is written here. Merely mentioning symptoms and age will not help patients whose doctors are focusing on the convenient number 20.

The >20 mIU/L cutoff will likely deny even “severe symptoms” the honor of being called “hypothyroid symptoms.” Even the younger adults will be told “you’re too young to have thyroid gland failure. You’re not in your 40s yet.”

Bekkering’s guideline-writing team had no basis to make the target so unreachable.

Feller’s review article, the main research basis of Bekkering’s guidelines, listed no less than ELEVEN limitations of their review as various populations to whom their review may not apply, and yet Bekkering only gave FOUR exclusions.

Feller and team said quite explicitly in their “Limitations” section that because only 2 of the 21 studies focused on people with TSH higher than 10, the findings of their review “may not be generalizable to people with subclinical hypothyroidism and a [TSH] level higher than 10 mIU/L.” (4)

— And yet the diagnosis was generalized to >20 mIU/L anyway!

DISMISSAL AND DELAY

Some of us thyroid patients have suffered years or decades being untreated because our Thyroid Stimulating Hormone (TSH) level did not rise high enough to qualify for thyroid hormone therapy.

Those of us who have finally attained optimized therapy look back with anger and disillusionment at the system that imprisoned us for so many years.

We could have listened to with compassion, we could have had access to a combination of relevant, cheap and available thyroid tests, and once we were finally treated, we could have had more effectively optimized therapies that made it more worth the long wait.

We could have been set free earlier.

Subclinical hypothyroidism has been defined variously in different times and places. The most permissive definitions define it as an elevated TSH concurrent with a Free T4 level that is within reference range. The most restrictive definitions have raised the TSH bar to 10 mU/L, which is far above today’s upper cutoff of approximately 4 mU/L. (3, 4)

And now the guidelines say doctors should delay treatment even longer for millions like us by raising the bar to more restrictive levels!

These new guidelines want to raise the TSH cuttoff from >10 mIU/L to >20 mIU/L. 

Over our years or decades of suffering, while our TSH was not high enough, our symptoms were continually dismissed as being non-thyroid related. According to the scripture of modern therapy guidelines, our symptoms are not truly thyroid symptoms unless the TSH rises high enough to declare that they are. (8)

TSH IS NOT THE JUDGE

Subclinical-Further-beyond-reach-TSH

In “subclinical hypothyroidism,” the TSH isn’t “high enough” and the Free T4 is not “low enough” to make us neatly fit into the extreme “clinical hypo” category.

Why is this arbitrary TSH diagnosis barrier getting raised higher and higher, from >10 now to >20? because the TSH test and the huge “normal” T4 reference range that define “subclinical hypothyroidism” are actually very blunt instruments, unable to identify patients whose glands have suffered enough autoimmune destruction and separate them from people whose gland IS being well stimulated by the TSH and IS producing more thyroid hormone. (5)

Anyone who knows the basics will understand that TSH is a secretion that calibrates itself in inverse relationship to T4 levels in blood. The end. The TSH is being used to judge our eligibility for thyroid hormone therapy because it happens to move a lot (it amplifies small changes in T4), and because the T4 hormone is tied to used in our therapy.

However, few realize that TSH is not a marker of the severity of hypothyroidism in tissues.

It’s not qualified to judge how hypo we are.

Meier and colleagues in 2003 discovered that “TSH is a poor measure for estimating the clinical and metabolic severity of primary overt thyroid failure” in untreated hypothyroidism. In other words, having a TSH of 20 does not mean your tissues and organs are less hypothyroid than those of your brother or sister with a TSH of 80. 

They concluded that “the biological effects of thyroid hormones at the peripheral tissues—and not TSH concentrations—reflect the clinical severity of hypothyroidism. A judicious initiation of thyroxine (T4) treatment should be guided by clinical and metabolic presentation and thyroid hormone concentrations (free thyroxine) and not by serum TSH concentrations.” (7) 

Neither TSH nor T4 are capable of activating thyroid hormone receptors in the nucleus of cells in every tissue and organ to activate genomic action there. Only T3 hormone can do that. (2)

Therefore, the invisible cause of our suffering is not TSH, and not even reduced T4, but a reduction in the most essential thyroid hormone of all, the T3 hormone, which never gets noticed by our health care systems–unless it’s too high.

Blood levels of T3 stay within reference range during untreated subclinical hypothyroidism. Therefore, in a medical system that only judges a lab test result by being “in or out of range,” a T3 deficit lies hidden.

Our drop in Free T3 is relative to our individual body’s needs, not relative to a range statistically derived from a larger population.

Even the physiological effects of tissue hypothyroidism like ankle reflex time would be a more useful test, a very affordable one, and a useful indicator in Meier’s study (2003). An ankle reflex simply measures how hypothyroid your tendons are in your ankles. If your reflex response is too slow, it correlates very strongly with low Free T4 and low Free T3, low “clinical score” (symptoms), creatine kinase levels, and total cholesterol, but it does NOT correlate with TSH at all. (7)

So what did they do, historically, with these tests of “tissue hypothyroidism”? They threw them out because they didn’t correlate with TSH!

“Tissue” hypothyroidism is not so “mild.” Reduced below our personal set point yet statistically “normal,” our T3 levels in blood and tissues render us progressively more and more symptomatic, fatigued, and depressed, with a huge list of additional symptoms, unable to function normally and sometimes unable to earn a living and maintain relationships.

In autoimmune thyroid disease, it can take decades for a thyroid gland to die an excruciatingly slow death from antibody attack. As the thyroid gland is gradually wrangled into a fibrosed mass of inert tissue, the TSH level creeps slowly higher, but it may creep too slow to satisfy our medical system.

If Mr. Pituitary isn’t hypothyroid enough or is too lazy to secrete enough TSH for us, the entire body beyond this tiny gland must not be hypothyroid enough.

In some, the T4 remains stubbornly in reference range, so we don’t look hypothyroid there, either.

The system is not interested in how much T3 we get out of our T4.

It is a horrid existence to be imprisoned within your body and have your medical system dismiss your suffering because your TSH is not high enough nor your T4 low enough to qualify you for rescue, and the real reason for your suffering is somehow beyond the detection of modern medicine.

TREATMENT WITH (ALL) THYROID HORMONES?

Subclinical-Further-beyond-reach-Levothyroxine

Bekkering’s new therapy guidelines not only raised the TSH level for a “subclinical hypothyroidism” diagnosis beyond reach for most adults, but they also falsely overgeneralized about ALL thyroid therapy modalities being equally ineffective in addressing hypothyroid symptoms and health problems.

Bekkering and team continually use the phrase “treatment with thyroid hormones,” plural. (3) Feller and team, whose research review they rely on, say “thyroid hormone therapy.” (4)

But we know that thyroid hormones used in therapy could involve T4, T3, or a combination of the two hormones, and they are very different in their effects.

All 21 trials reviewed by Feller were about ONE form of thyroid therapy alone — synthetic T4 hormone (levothyroxine). (3)

Neither research article mentioned the hormone medication “T3,” (liothyronine) nor desiccated thyroid extract (DTE / NDT), which contains T3 and T4.

Neither Feller’s review nor Bekkering’s guidelines mentioned that T4 is the largely inactive hormone that the body must convert into T3, the active hormone, and that T3 is a far more potent and potentially far more effective medication. (2, 10)

Neither the guideline nor the research review had the right to generalize beyond the ineffectiveness of levothyroxine monotherapy in the treatment of thyroid disease.

Only the BBC article writer happened to mention T3 therapy, but in a limited manner, as a “more expensive drug,” not mentioning anything about its greater potency and effectiveness in therapy. (1)

These guidelines are part of a problem that all hypothyroid patients face, not just those with subclinical hypothyroidism, with regard to our pharmaceutical options and the effectiveness of our therapy.

T3-based therapies were once the gold standard of thyroid therapy until the 1970s when levothyroxine took hold of the market and the minds of endocrinologists.  (6) Since then, the medical professions have made it difficult to reintroduce these pharmaceuticals, but they still enjoy success and favor among thyroid patients globally (11).

Most hypothyroidism therapy guidelines deny T3 hormone therapy to the vast majority of patients. (8) As I’ve argued elsewhere, this is largely based on endocrinologists’ pharmaceutical prejudice against desiccated thyroid extract, fear of T3’s potency, and preference for synthetic T4.

As a result of these modern restrictions, patients are told that they can’t expect relief from symptoms and chronic health problems, only normalization of TSH, from today’s “standard of care.” (8)

When will our thyroid therapy gods stop contradicting themselves?  When they want to push their favorite medication on us, they say it is “effective.” But when they want to take all thyroid hormones away from people whose TSH is not high enough and T4 not low enough to qualify, they then find it convenient to say levothyroxine is “ineffective” at removing our symptoms and therefore we should not receive ANY.

THYROID HORMONES ARE INEFFECTIVE?

Let’s think about this critically. We all have thyroid hormones flowing through our bodies. If we did not have thyroid hormones, we would die. Therefore, thyroid hormones are very effective at keeping us alive.

All our advanced science and pharmaceutical technology assures us that the synthetic thyroid hormones we obtain from pharmaceuticals are truly bioidentical to naturally secreted and converted hormones.  So, why on earth would they all be ineffective at supplementing thyroid hormone for people who can’t make enough thyroid hormone?

Obviously we’re not getting the right combinations, ratios and amounts of thyroid hormone. Something is wrong with the therapeutic system. Don’t throw out the hormones along with your broken therapy guidelines!

May we as patients point out the ways your system is rendering thyroid therapy ineffective at giving us the most essential thyroid hormone, T3?

Medical prejudice against the larger T3-T4 ratio in an effective, historic thyroid pharmaceutical, desiccated thyroid extract, has led to a series of limited-ratio LT3-T4 combination therapy trials. (9) Unsurprisingly, limited ratios are limited in effectiveness at resolving hypothyroidism, but larger ratios such as 1:5 that are more effective (10) are frowned upon as containing too much T3. (9) These limited results have limited the number of T3-based therapy prescriptions. This has led to the removal of limitations on the market price of synthetic T3 (liothyronine), especially in the UK. And ultimately, this means that “costly” T3 is being denied to many patients.

If the system keeps on limiting access to thyroid pharmaceuticals and limiting its T3 ratios in clinical trials and clinical practice, what can they expect other than limited effectiveness? (9)

If the tiny amount of T3 that has been permitted to date in clinical trials is going to be effective on any hypothyroid patients, why would it not be effective in the treatment of subclinical hypothyroidism?

But instead of going down that productive path of making therapy more effective for some, if not all, thyroid patients, they’ve made guidelines that use sweeping language that damn even T3-based “thyroid hormone” therapies to futility, and even worse, unmentionability.

DON’T LIMIT OUR THYROID HORMONES

This is a slap in the face of suffering thyroid patients:

“Thyroid hormones do not lead to important benefits for adults with subclinical hypothyroidism for quality of life or thyroid related symptoms including depressive symptoms and fatigue.”(3)

No, we know this is false.

We see something very different among our peers.

Some thyroid patients have actually suffered long and fought hard to seek out and obtain a thyroid hormone therapy that IS more effectively optimized to our T3 hormone requirements. (11)

Your increasingly restrictive diagnosis guidelines and your refusal to even mention the existence of T3-based therapy options are part of the system that is making a superior, effective therapy beyond the reach of millions of suffering patients.

— Tania S. Smith

REFERENCES

  1. BBC. (2019, May 15). Thyroid disease “being over-treated.” Retrieved from https://www.bbc.com/news/health-48265023
  2. 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
  3. 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
  4. 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
  5. Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2016). Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function. Frontiers in Endocrinology, 7. https://doi.org/10.3389/fendo.2016.00142
  6. McAninch, E. A., & Bianco, A. C. (2016). The history and future of treatment of hypothyroidism. Annals of Internal Medicine, 164(1), 50–56. https://doi.org/10.7326/M15-1799
  7. 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
  8. Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., … Sawka, A. M. (2014). Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid, 24(12), 1670–1751. https://doi.org/10.1089/thy.2014.0028
  9. Wiersinga, W. M., Duntas, L., Fadeyev, V., & Nygaard, B. (2012). 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism. European Thyroid Journal, 1(2). https://doi.org/10.1159/000339444
  10. Appelhof, B. C., Fliers, E., Wekking, E. M., Schene, A. H., Huyser, J., Tijssen, J. G. P., … Wiersinga, W. M. (2005). Combined Therapy with Levothyroxine and Liothyronine in Two Ratios, Compared with Levothyroxine Monotherapy in Primary Hypothyroidism: a Double-Blind, Randomized, Controlled Clinical Trial. The Journal of Clinical Endocrinology & Metabolism, 90(5), 2666–2674. https://doi.org/10.1210/jc.2004-2111
  11. Peterson, S. J., Cappola, A. R., Castro, M. R., Dayan, C. M., Farwell, A. P., Hennessey, J. V., … Bianco, A. C. (2018). An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction. Thyroid, 28(6), 707–721. https://doi.org/10.1089/thy.2017.0681

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