The current model of long term thyroid therapy reduces it to two simple buttons or levers on a machine:
- Test TSH
- Dose L-T4 to fix the TSH
Wow, the power of science! We’ve got hypothyroidism fixed! Cured!
It appears that doctors enjoy the satisfaction of “normalizing” the TSH hormone secretion by the L-T4 dose. It’s like driving between the lines.
Like kicking a football between the goalposts. Job done!
The TSH numbers can give medical professionals a superficial illusion of control. Looking at TSH and T4 alone blinds a doctor to the state of the end-product hormone, T3.
What does the cardiovascular system respond to the most, TSH, T4 or T3? A researcher of thyroid and heart disease would say, T3, undoubtedly, both low and high T3, and even subtle changes within the normal reference range of T3 can make a huge difference.
The simple model is scientifically naive. Calling it “thyroid hormone replacement therapy” promulgates the belief that L-T4 medication can replace living thyroid gland tissue. Sorry, it’s not like vitamin D supplementation. It’s this belief that makes doctors imagine L-T4 medication taken orally merely “replaces” T4 from a thyroid gland with T4 from a pill.
Unfortunately, the thyroid – pituitary axis is not designed to respond “normally” to artificial therapy.
Pituitary TSH secretion is wired to respond to T4 by assuming that it is coming from a healthy gland that is simultaneously secreting some T3 at the same time. This is not true anymore in a patient with thyroid gland dysfunction or removal. Up to 20% of one’s daily T3 supply (secreted directly from the thyroid) disappears when the thyroid is removed or is killed by autoimmune attack.
Supplementing with T4, therefore, can “trick” or artificially manipulate the pituitary’s secretion of TSH, and thus bias the TSH test results, causing TSH to ignore a concurrently suboptimal T3 thyroid hormone level.
It seems to work like a charm at first, especially if a patient was severely hypothyroid without therapy. Adding T4 reduces and “normalizes” the TSH. But many patients are less than charmed by the results they live with every day for years, no — for decades. But becasue the TSH has been artificially “normalized,” the patients are told that can’t possibly be their thyroid levels, but some other illness, causing their hypothyroid symptoms.
The simple model assumes that because our technology to measure TSH is sensitive down to 0.001 that it is the best and only indicator to measure. It assumes one hormone is able measure two other hormones’ levels. It assumes TSH knows all about hormone levels not only in blood, but in peripheral tissues like bones and brain.
The simple model is based on the beautiful interaction of the pituitary gland and the thyroid gland in thyroid health, NOT in thyroid disease and artificial treatment. We are measuring injured, medicated people by the yardstick of health and nature. We are not looking under the carpet to see all the dysfunction going on underneath.
How many of those symptomatic patients are determined to be euthyroid because of their TSH alone, rather than on the basis of their _thyroid_ hormone levels and other trustworthy biomarkers?
TSH is unquestioned because the system has eliminated the collection of data that does have the power to prove the TSH or the L-T4 therapy questionable, misleading, or harmful in a given patient.
Let’s examine how this simple TSH-T4 model breaks down in reality.
In patients on L-T4 monotherapy, the healthy HPT axis model breaks down even at the level of the TSH-T4 relationship.
In thyroid disease, the 2-way feedback loop is no longer truly 2-way. It’s interacting with a damaged gland (if any remains) AND a static, synthetic hormone dose of only one hormone. It’s really more complicated now.
L-T4 dose now directly manipulates TSH secretion in response to that dose. Therefore, in a treated thyroid patient, to the degree that their thyroid gland is defunct, TSH is no longer in direct control over their T4 level within the normal reference range.
In thyroid patients, the TSH cannot “regulate” or fine tune their T4 levels. If the patient is colder in wintertime and TSH rises, will T4 rise and help them warm up? No, not until they see their doctor for their yearly checkup. Thus, TSH is reduced to its role in medical practice as a respondent, not regulator. And it is medically perceived as a very broad “indicator” with three categories (high, low, normal). No fine-tuning for you, thyroid patient. Normal can be a TSH of 3.99, so no dose increase for you until it is 4.1, or maybe higher.
We even have to wait at least six weeks for TSH to “equilibriate.” That’s an euphemistic way of saying that TSH is very sluggish in response to T4 dose changes, and that TSH is giving us a broad ballpark average of T4 levels over the past 6 weeks. If it’s a ballpark average, why would a doctor make a dose change based on a difference of +/-0.1 TSH? Because it’s the only hormone measured, and it’s given such complete trust, that’s why.
I hate to break the bad news, but science has not fully replaced an adaptible gland with a static pill.
To skew it even more, TSH is an indicator that can be biased toward one thyroid hormone more than another, depending on the mode of hormone therapy selected.
In L-T4 monotherapy, TSH follows T4
In L-T4 treated thyroid patients,
- TSH usually indicates T4 level. TSH is reduced to being a mirror image of the dose when there is no living thyroid gland tissue.
- TSH has no direct relationship to T3 hormone levels to the degree that there is a low T3:T4 ratio. TSH becomes blind to T3 when T4 is higher. When there are mixed messages, and T3 is only whispering, it listens to T4 shout.
- At the same TSH and T4, thyroid patients on L-T4 monotherapy have T3 levels that are lower, on average, than in healthy subjects. These thyroid patients do not have T3 levels equal to the rest of the human population.
In other words, there is a clear TSH-T3 disjoint in patients on L-T4 therapy (Hoermann et al, 2015). In L-T4 monotherapy, it’s also a pill containing the less active of the two hormones. That imbalance has consequences when you look at the 3-way relationship between the hormones.
Thyroid disease itself deepens this TSH-T3 disconnect.
To the degree that L-T4 treated patients have very little or no thyroid tissue (either due to thyroidectomy or autoimmune destruction), TSH can be very misleading about the patient’s true T3 status, which ultimately determines their thyroid hormone health. Functional thyroid capacity becomes an important factor. In thyroid patients, TSH alone cannot respond to, predict, or indicate high, low, or normal T3 levels (Hoermann et al, 2013).
Here’s two crucial paradoxes that make TSH fallacious in L-T4 monotherapy:
- A person with a “normal” TSH suppressed by higher T4 levels could be hypothyroid in their T3 level. A T3 level that is too low in relation to the patient’s “set point” can independently cause biochemical hypothyroidism and put a patient at risk of illness and an early death. Read our sections on Rationale: Free T3 testing and Rationale: Low T3 Syndrome, part 1.
- A person with a completely suppressed TSH may have euthyroid levels of T4 and T3 and absolutely no sign of hyperthyroid metabolism or other telltale signs of overstimulation of tissues by T3 hormone. We see euthyroid levels frequently in patients after high-risk thyroid cancer, when TSH is intentionally suppressed because TSH is known to cause cancer to return. These patients cannot be rendered hypothyroid by their TSH alone. They are genuinely hypo or hyper only in relation to their thyroid hormone levels, not their pituitary hormone level.
What to do? Monitor Free T3.
Doctors, a lifelong thyroid patient needs you to care for her whole body’s supply of T3 hormone over years and decades. She needs more than a monitor of the rate of her pituitary TSH secretion. If you are giving her T4, make sure it’s still converting at a good rate when she becomes chronically ill or goes on an extreme diet.
The most important biochemical parameter is T3. It is the only thyroid hormone that can stimulate genomic activity in the thyroid hormone receptor.
You can’t be biochemically, truly hyper without T3 levels above your set point, and you can’t be hypo without T3 below your set point.
Therefore, it is necessary to measure Free T3 and Free T4 and to pay attention to all signs and symptoms, not just the superficial observer, pituitary TSH, that can be “tricked” by the artificial, pulsatile nature of oral hormone dosing.
Don’t make TSH an idol.
The pituitary gland is only one part of the body.
The pituitary gland assumes the person has a normal thyroid gland. It hasn’t got the memo that the gland is missing or seriously damaged.
Any form of thyroid therapy is artificial and manipulates the TSH-T4-T3 relationship in unusual ways.
The pituitary gland assumes that the T3 and/or T4 it senses in blood is being secreted and converted naturally, not taken in pulsatile doses through the GI tract. It mistakenly thinks “I’m stimulating a gland that can secrete T3, so this person should be fine with this much T4.”
The pituitary cares for its own needs first and foremost. The pituitary can live on T4 alone because it can convert enough T3 within its own tissues in a state of T3 deficiency in blood.
The pituitary gland could frankly care less if the rest of the body starves from T3 depletion. It’s not in charge of the deiodinases that convert thyroid hormones. It blindly assumes that T4-T3 conversion is occurring normally even if Deiodinase Type 3 is stealing both thyroid hormones.
Unfortunately, in our current system, the doctor is trained to treat and normalize the pituitary gland, not the patient’s thyroid hormones, by measuring the TSH and obeying it alone.
Twenty years from now I hope science will look back at the TSH-T4-only phase with amazement and regret. How sad that we put all patients through the extremes of a monotherapy by default, and that we only bothered to measure the finicky spectator hormone, the TSH.