This post continues our opening series on “Developing Infographics for thyroid testing.”
In this post I discuss the scientific basis and potential usefulness of a meme on “Tests to optimize thyroid therapy.”
In this infographic, we stand firmly on the basis of science when we disagree with our current medical systems’ dogma.
It is utterly mistaken to claim that mere TSH normalization is capable of determining that thyroid therapy type or dosage strength is “adequate” to treat an individual’s hypothyroidism.
Screening is not monitoring.
You don’t use the same flowchart to diagnose a car and repair the car.
If you are fixing a car, you can’t just skip from “screening” to “monitoring.”
There’s a crucial step in the middle, right after the diagnosis.
We must return to that middle step whenever problems arise and adjustments must be made. In a lifelong therapy, health conditions change. Now and then one must optimize and recalibrate thyroid therapy. A top to toe thyroid hormone tune-up is necessary, and usually all it takes is measuring Free T3, Free T4, and TSH together.
The idolization of TSH is harmful to thyroid patients. There is no single laboratory test, not even T3 or T4 in isolation, that can accurately identify all forms of hypothyroidism.
Instead, we propose a more rational, evidence-based hierarchy of thyroid tests to adjust and optimize thyroid therapy ratios and dosages whenever adjustments are necessary.
Prioritize the most essential and trusted biomarkers in therapy
Therapy can be optimized to the individual if we prioritize the hormones appropriately.
The trio of TSH, FT4 and FT3 tests are at the core.
Among these tests, the two hormone tests are the most essential. Why?
First of all, because TSH is compromised by far too many common and frequent conditions, from simple fasting to vitamin A overdose, glucocorticoid excess.
Secondly, among the smaller population of patients already officially diagnosed with thyroid diseases, one ought to expect a relatively higher than normal incidence rate of the rarer conditions that compromise TSH, such as Graves’ disease antibodies, hypersecreting thyroid nodules, chronic nonthyroidal illnesses like heart failure, diabetes, and cancer, hypothalamic compromise, pituitary failure, and genetic mutations affecting pituitary thyroid hormone signalling.
We ought to begin with the most powerful and essential thyroid hormone T3, which goes hand in hand with its parent hormone T4, and they are never properly interpreted in isolation from each other.
The error of ignoring T3-T4 relationships is most powerfully proven by the extreme of LT3 monotherapy (Cytomel, liothyronine alone). This last-resort form of therapy has been practiced ever since LT3 became available in 1952 as a pharmaceutical. Rare thyroid patients will experience significant difficulty with all other thyroid therapy options but this one. Their medical histories prove that the human body can be maintained in a euthyroid, healthy state for years or decades on LT3 alone, without cardiovascular problems, mental health problems or bone health problems, despite a complete absence of T4 hormone in circulation. The only requirement is that significantly more than normal levels of T3 must be in circulation to compensate for lack of T4, and frequent dosing must maintain sufficient equilibrium.
Then TSH comes in second place, and thirdly comes the option to test Reverse T3, the third most abundant thyroid hormone after T4 and T3.
First FT3 and FT4
Attention to T3 in context reveals the weaknesses and strengths of all therapies, including standard LT4 monotherapy, all ratios of T3-T4 combination, desiccated thyroid, and LT3 monotherapy.
Rudolf Hoermann and team have recently published a study (2020) showing how to optimize LT4 therapy to remove hypothyroid and hyperthyroid symptoms. It is built on a firm foundation of years of diligent research and scientific review.
They have found that optimization of LT4 thyroid therapy hinges on a Free T3 supply around mid-reference range.
Naturally, the Free T4 must be higher in its range on Levothyroxine monotherapy to achieve the net T4-T3 conversion rate that supplies enough Free T3 to all organs and tissues. Each patient’s FT3:FT4 ratio is dependent on their unique response to levothyroxine at various doses. Populations of thyroid patients classified by disease etiology reveal the FT3:FT4 ratios of a range of poor, moderate, and good converters of T4 hormone.
Principles for optimizing LT4 monotherapy can also be applied, with rational and scientific modifications, to other thyroid therapies that include T3 hormone.
Second, TSH in context.
In thyroid therapy, the TSH can’t optimize anything on its own; the lever and wiring on its thermostat is broken and it does not drive the furnace.
Hoermann and team have illustrated the significant alterations of the HPT Axis between the untreated state and LT4 thyroid therapy.
In thyroid disease and therapy the HPT axis is no longer a closed feedback loop, but rather a broken and unnatural open loop with new inputs.
Our hormone economy is no longer a naturally TSH-driven in partnership with a healthy thyroid gland that secretes and converts at a flexible rate every hour of every day.
Instead of being driven and guided only by TSH, therapy’s axis is driven by a complex of new forces:
- pulsatile oral dosing via the GI tract, not gradual intravenous infusion,
- variable degrees of disabled remnants of living thyroid tissue that still respond to TSH, but may also secrete autonomously (functioning thyroid nodules)
- the presence or absence of two types of TSH-receptor antibodies that can block or mimic TSH, and
- the loss of thyroid tissue’s T4-T3 converting D1 and D2 enzymes that used to be able to make up for any shortfall in bloodstream T3.
Hoermann’s team’s research findings on the lower TSH necessary to optimize T3 levels and signs and symptoms of euthyroidism has been independently corroborated by Matsuru Ito’s team in Japan from 2012 to the present.
Therapy is not well optimized by TSH response, yet in order to achieve optimized T3 hormone levels for global euthyroid status, TSH must be permitted to fall lower in patients with less thyroid tissue who need higher doses.
Therefore, the TSH in therapy is subordinated, not overruling, never an independent indicator of adequate dose. The TSH must always be interpreted in the context of Free T3 and Free T4 levels and ratios if one wishes to optimize thyroid hormone metabolism, not merely achieve a superficial semblance of TSH normality. Therapy is about benign intervention in an individual’s disease, not the imitation of statistical norms of TSH biochemistry.
Optional: Reverse T3
Thyroid science reveals a rational role for RT3 as a troubleshooting test.
It matters how much T4 from dosing and secretion is going into the metabolic dustbin. Our RT3 is always best interpreted in relationship to its origin hormone T4 and its alternative metabolite T3. It indicates the rate at which T3 is also being lost to 3,3′-T2 by the same D3 enzyme.
We have a mountain of T4 that is barely diminished by conversion to RT3, but we have precious little T3 we can ill afford to lose when it’s low in range. Our loss of T3 to this inactive form of T2 is a far more significant loss.
There’s no T2 test, but RT3 comes close to being the shadow of one.
Patients usually pay for the RT3 test out of pocket because they really want to know. However, we must not put the cart before the horse and judge input and health outcomes by a tertiary byproduct.
RT3 is a flag, not a powerful lever. It’s not an evil hormone we must reduce at all costs.
An entirely separate series of infographics must address the mistaken myths and fears about Reverse T3 that are troubling many thyroid patients.
Now we can talk about monitoring.
If cost savings are desired, once therapy is stabilized, one can test only the one or two hormones that are
- likely to change from test to test, AND
- involve significant health risks when falling too low or rising too high.
No FT4 test if: T4 intake and absorption is constant and has never been a problem.
No TSH test if: the therapy necessitates full TSH suppression and it is expected. You know the TSH is going to be suppressed when FT4 and FT3 are either or both high enough to eliminate hypothyroidism, so why check TSH again and again?
No TSH test if: the TSH is neither trustworthy nor reasonable in the individual. This may be due to central hypothyroidism, resistance to thyroid hormone (RTH), or people with fluctuating high TSH during therapy despite high-normal thyroid hormones, due to active TSH-receptor blocking antibodies.
Health reasons to test FT3
The individual is dosing LT3 hormone alone, or dosing LT4-LT3 combination or desiccated thyroid at levels that make FT3 fluctuate significantly. (test after the volatile FT3 peak ideally 12hrs post dose)
T3 conversion to 3,3′-T2 fluctuates due to chronic or critical illness,
Health reasons to test FT4 and FT3 together
Medications and health conditions can significantly alter FT4 absorption and thus both the FT4 and downstream FT3 concentrations.
TSH-receptor antibodies coexist with partial thyroid gland function and/or secreting thyroid nodules, producing unexpected variable levels of T4 secretion, T3 secretion and T4-T3 conversion within the thyroid gland.
Medications and substances are added or removed which can impact Free:Bound hormone ratios (estrogen dosing), T4 absorption through GI tract, and T4-T3 metabolism. Both hormones’ levels and their ratio can be significant for health and can alert the physician to the need for an adjustment.
No excuse to cancel Free T3 during therapy.
No genuine scientific basis exists to eliminate the FT3 test in the context of thyroid therapy.
In fact, biology never takes its eyes off of circulating T3.
Abdalla and Bianco in 2014 boldly announced that dogma has been looking at thyroid hormones backwards, and we must shift to a T3-centric paradigm.
In thyroid disease and therapy, the levers, buttons, cogs and wheels of TSH and T4 don’t work the same way, but T3 is still the most precious part of our thyroid hormone metabolism.
Neither TSH nor FT4 concentration predicts the FT3 level during LT4 thyroid hormone therapy.
In the graph below, FT3 levels from 3.5 to 7 or higher are seen at all TSH level of 2.00 or lower. The FT3 could be anywhere at any of these TSH levels.
If you think TSH is a good proxy for both T3 and T4 during therapy, you might as well wear a blindfold and play a game of “pin a tail on the donkey.”
FT3 levels and local T4-T3 conversion is only well-regulated by the un-manipulated partnership between TSH and healthy thyroid tissue. Tissue T3 is only secured by health:
- if the patient is NOT dosing thyroid hormone and
- if the patient is free of TSH-receptor antibody interference
- if the patient has enough thyroid gland function and pituitary function
- if the patient is capable of overcoming temporary (acute, benign) tissue hypothyroidism (nonthryoidal illness).
As soon as a patient is on thyroid therapy, the HPT axis can experience unnatural interference at every level, and the FT3 is at risk of being poorly regulated by dosing and metabolism. The TSH and FT4 can be blind to falling FT3 levels even if the person is taking a low dose of hormone such as 25 mcg LT4.
Opinions that FT3 concentrations are irrelevant to health outcomes do not rest on a scientific basis. They rest on dogma.
The fact that “each tissue and organ converts T4 and T3 at a variable” rate does not negate the fact that each tissue and organ depends on enough Free T3 in circulation to “top up” local T4-T3 conversion rate.
The expectation that FT3 will likely be “in range” is not good enough to avoid testing, because FT3 levels can be insufficient or in excess for the individual within the reference range, and “enough” T3 always depends on the availability of FT4 as well as one’s metabolic homeostatic setpoint.