When is Low TSH not hyperthyroidism?

pituitary glandQ: When is a low TSH not hyperthyroidism?

The answer is huge — in central hypothyroidism, in low T3 syndrome, in the first trimester of pregnancy…

AND in cases where thyroid therapy achieves euthyroid status without causing tissue thyrotoxicosis.

In many posts on this blog, we’ve detailed the reasons why TSH is a poor indicator of thyroid hormone excess, deficiency or balance.

We’ve also explained why it’s not a sole judge of adequate dosing in thyroid therapy.

This post has been edited in July 2019 to tie many of these insights together.

TSH alone can’t define hyper- or hypothyroid status

The official thyroid-textbook definition of thyrotoxicosis is not TSH-dependent.

“We use the term thyrotoxicosis to mean the clinical syndrome of hypermetabolism and hyperactivity that results when the serum concentrations of free thyroxine (T4), free triiodothyronine (T3), or both, are elevated.” (Braverman & Cooper, 2013, from Werner & Ingbar’s The Thyroid )

Biologically, several problems make it impossible for TSH alone to define true euthyroidism, especially in thyroid therapy:

  1. TSH is a signal of thyroid hormone sufficiency only in the hypothalamus and pituitary glands. These glands are not omniscient (all-knowing) about thyroid hormone levels in your brain, heart, liver, or bones. Thyroid hormones in these other organs may be either deficient or optimal when TSH is low, because:
  2. New thyroid science teaches that every organ and tissue in the human body converts T4 into T3 (or Reverse T3) and converts T3 into T2 at its own unique rate. The hypothalamus and pituitary are not an exception to this rule. If the TSH signals that the hypothalamus and pituitary have enough T3 supply from local thyroid hormone conversion, that does not mean your heart or brain converts thyroid hormone in the same way or at the same rate. What ensures that all organs have enough thyroid hormone supply? Bloodstream levels of FT3 and FT4. This is because:
  3. All tissues exchange Free T4 and Free T3 hormones with bloodstream in both directions, taking these hormones in, converting them, and then transporting them out again into blood at varying rates. Therefore, thyroid hormone levels you see in blood represent the balance of ALL your organs and tissues’ exchange of thyroid hormones with bloodstream every minute of every day. If a low TSH contradicts normal or low thyroid hormones in blood, then the TSH is the exception, not the rule, and certainly does not represent the average rate of conversion.

TSH molecules have their main purpose and action by entering TSH receptors located on the thyroid gland and elsewhere in the human body.

TSH does not enter _thyroid hormone_ receptors throughout the body. Only T3 can enter thyroid hormone receptors in the nucleus of cells and have essential genomic activity there.

A lack of TSH by its very definition cannot overstimulate T3 hormone receptors throughout your body — only a significant oversupply of both T4 and T3 in bloodstream can do that.

TSH levels alone do not cause disease or disorder

Doctors are told that a low TSH puts a patient at “risk” of osteoporosis, but in fact, a high percentage of association does not prove causation. See reviews of thyroid science:

The experts in thyroid & bone health point out that TSH plays less of a role in bone cells than local T4 and T3 hormone conversion.

Supplying your body with TSH molecules will not help your bones if you have a deficiency in T3 + T4 in bloodstream. Some bone cells require FT3 from blood supply because they cannot locally convert T4 into T3. However, almost all bone cells have a way of neutralizing mild T3 excess.

The risk of cardiovascular disorders also comes up with low TSH, but if you read articles about Thyroid and Heart, they are not about the direct effects of TSH. The functional connection between cardiovascular disorders and thyroid hormones is ALL about T3 excess or deficiency.

Beyond the fact that TSH hormone is needed to stimulate a healthy thyroid gland to secrete sufficient T4 and T3 hormone, there is little proof that other organs and tissues are harmed by the absence of TSH.

This is proven by the case of many thyroid patients in many decades of history maintained by TSH-suppressive therapy who did not ever develop osteoporosis or heart disease. If lack of TSH by itself was a cause of harm, then it would be impossible for any of those patients to have maintained healthy lives, and yet so many of them were fine.

TSH can be biased too low even in people with healthy thyroid glands who are not taking thyroid hormone medication. While bloodstream and many tissues in the body suffer low T3 levels, the TSH falsely indicates that thyroid status is normal in fasting, exhausting exercise, and many other health conditions.

For more proof that TSH is not an independent indicator of thyroid hormone status:

The healthy HPT axis is different from the medicated HPT axis.

In healthy human beings, it is the FT3 level, not the TSH level that is carefully defended in bloodstream (Abdalla & Bianco, 2014).

In contrast, a thyroid patient cannot easily “defend” their FT3 levels in blood over time because they lack enough healthy thyroid gland that is being regulated by TSH. 

The damage, death or removal of a thyroid gland breaks the HPT axis and tries to fix it by using hormone medication.

In thyroid therapy, the doctor’s dosage of thyroid hormone directly manipulates the TSH. 

In thyroid therapy, the TSH can no longer drive health outcomes because it does not regulate a healthy thyroid.

TSH isn’t itself a health outcome. It is not even a good proxy for health outcomes. 

TSH was not intended by nature to be the sole judge of a medicated person’s full-body thyroid hormone status. We in modern science have forced it to play this unnatural role.

TSH’s natural role is not to judge, but rather drive, natural thyroid hormone supply.

In T3-based therapy, TSH is hypersensitive to T3 oral dosing

In therapies using desiccated thyroid extract (DTE / NDT) or synthetic T3, it is well known that oral dosing has a more powerful TSH-suppressive effect than T4 at an optimal dose.

Snyder and Utiger discovered this in 1972 through experimentation, and stated this about a ratio of  T3 and T4 thyroid hormone equal to that found in desiccated thyroid:

“A replacement dosage of thyroid hormone, one sufficient to maintain a hypothyroid patient in a euthyroid state with a serum TSH level that is not elevated, is generally also a suppressive dosage, capable of suppressing TSH secretion below normal.”

They found that for each patient the TSH level suddenly dropped to subnormal when they finally achieved an euthyroid dose. Therefore, dosing by the TSH test is a sure way to make desiccated thyroid therapy and other T3-based therapies fail to achieve more than just “pituitary euthyroidism.”

When transitioning from L-T4 therapy to L-T3, the TSH is often suppressed long before the patient becomes euthyroid in their thyroid hormone levels. Read about this in

Sadly, the doctor uninformed of this pharmacokinetic effect puts on the breaks as soon as the TSH meets its lower boundary of the “normal” reference range.

While the pituitary gland may be satisfied with the dose and is having a coffee break, the rest of the patient’s body could be biochemically hypothyroid or euthyroid.

Oral dosing of T3

A lower TSH is a side effect of the pulsatile nature of artificial T3 dosing through the GI tract.

Science has known for some time that the hypothalamus and pituitary gland are very watchful of “high” T3 levels, and they respond even more quickly to T3 than they do to high T4.

In addition, the HPT axis model does not consider the role of T2 in suppressing TSH.  T2 is the direct byproduct of T3, and T3 may convert to T2 at a higher rate than normal after a dose.  The thyroid hormone T2 has a powerful effect on TSH suppression in the laboratory setting, according to Padron et al, 2014. Its effect is independent of T3 levels. T2 administration suppresses TSH by raising T4-T3 conversion within the hypothalamus and pituitary gland.

As a result of this “dual action” of T3 oral dosing, even before Free T3 levels rise to their peak in serum, TSH may be suppressed.

Once TSH drops from this trigger, TSH remains suppressed for days (Jonklaas et al, 2016). These are days that the patient could be hypothyroid despite the continued low TSH.

Therefore, if you listen to the pituitary gland’s TSH alone, you are listening to what the pituitary thought of the brief time following the patient’s oral dose.

If the doctor measured their Free T3 in a blood test, how long after the dose was it measured? As a result, will the T3 measurement be biased toward the tiny peak or the huge valley? If you bias measurement toward the tiny peak, you bias therapy against the patient’s long-term T3 thyroid hormone status.

Does the Peak Free T3 harm the patient?

Not likely, unless it is unreasonably huge and frequent.

Robert Utiger, who studied these peaks and valleys in T3-based thyroid therapy, wrote “These fluctuations in serum T3 levels must be sufficiently attenuated at the tissue level that such a sensitive indicator of tissue thyroid hormone action as TSH secretion is constant despite the widely varying T3 concentrations which follow once daily T3 administration.”

Notice their wording — the “fluctuations” are “sufficiently attenuated at the tissue level” — attenuated means “reduce the force, effect, or value of.” In other words, they theorized that the peak T3 above reference was being buffered or weakened within tissues. The large wave (the peak) was being reduced to a small wave by the time it reached the hypothalamus and pituitary shores — the “shores” are the T3 receptors within the nuclei of cells.

The height of the peak is based on many factors — the patient’s baseline level and the dose size. The best approach is to measure the patient’s baseline Free T3 levels and consider their thyroid signs and symptoms before writing the prescription.

Peak Free T3 is not sustained as it is in true hyperthyroidism

Studies show that oral T3 has a short half life in the body, likely even shorter than T3 that is secreted or converted 24/7 gradually.

In Jonklaas et al, 2016, euthyroid subjects tested on one dose of 50mcg (which is a lot for an “euthyroid” person to take all in one dose), blood levels of T3 fall rapidly and are almost at baseline by 12 hours, and then there’s a long tail on the graph as the last molecules take longer to dissipate (again, see Rationale: L-T3 dosing effects).

  • This is unlike levels of T4, which maintain themselves in bloodstream for weeks, and if T4 is high it can remain dangerously high for quite some time.
  • This is also unlike the hyperthyroidism found in Graves’ disease, which causes a constant oversupply of T3 caused by TSH-receptor stimulating antibodies that continually stimulate the thyroid gland to produce T3 and T4 — even when TSH is absent.
  • Is the T3-treated patient’s metabolic rate continually elevated every hour of every day like the Graves’ disease patient? Ask the patient to measure. Find out before assuming it is constantly elevated.

Peak Free T3 is brief because D3 turns it into T2

The patient’s body has a way of quickly dealing with excess thyroid hormone, both T3 and T4: it’s called Deiodinase Type 3 (D3).

Deiodinase type 3 protects the body by converting any excess T3 into T2 as quickly as possible, and perhaps that’s why levels fall so rapidly after a dose. In patients treated with T3, the levels of T2, which is its byproduct, may be temporarily elevated for this reason.

Also, according to Padron et al, 2014, having more T2 hormone has a good side effect for patients struggling with obesity due to hypothyroidism: it increases energy expenditure and reduces excess fat, at least during the time T2 is elevated.

Ask this: How much T3 does it take to stimulate D3? When it does, how much is being converted to T2 within the first few hours of a dose? Do the research before assuming greater harm occurs within those few hours a day than occurs from years of continual T3 deficiency.

Peak Free T3 is brief because of hormone binding

Science tells us that as Total T3 rises, more of it is bound to carrier proteins rather than free.

Bound L-T3 is not going to harm the patient as much as excess free T3.

How much synthetic L-T3 is taken in as free hormone? How long does it take to be bound to carrier proteins? Do the research to find out, rather than being fearful of something we do not yet know.

Peak Free T3 does not seem to cause long-term harm

Look into the history of T3 therapy and desiccated thyroid therapy. Find out by reading the history of T3-based therapy in articles before the TSH test overruled the definition of hyperthyroidism.

They used to treat patients until they achieved “euthyroid status” in terms of their overall signs and symptoms. You may be surprised at the DTE/ NDT or T3 doses they were maintained on.

When historical medical articles occasionally reproted adverse cardio-metabolic effects on T3-based therapies because of dosing errors, the fact that such effects were reported in research meant they were abnormal or temporary. Mistakes in dosing were of course not maintained over the long term.

Therapy is mainly about T3, not TSH.

As thyroid patients, we would like to see doctors seriously fear suboptimal T3 as much as they fear excess T3. The fear of low TSH is leaving many treated thyroid patients in unnecessary suffering with suboptimal T3 for years and decades.

True hyperthyroidism caused by thyroid hormones does not lie undetected under a low TSH. It has clear metabolic manifestations.

Cardiovascular manifestations occur with higher as well as lower Free T3. When a person has been low in Free T3 for a while, raise doses gradually or it could be too overwhelming for their fragile state.

If hyperthyroidism is temporarily caused by dosing errors, it can easily be fixed by reducing the dose.

If the patient is still hypothyroid on therapy, there is no reason why one should not aim or the middle or upper normal range of Free T3 as long as FT4 is not concurrently high-normal or elevated.

You’ll know when the patient is optimal on their therapy when their sufficient T3 and T4 relieves as many signs and symptoms of hyperthyroidism and hypothyroidism as possible. This is the way to achieve true and healthy metabolic balance for a lifetime of therapy.

REFERENCES

Many of the references for this post are in the links embedded in the post itself.

These three items were the only ones that are not freely available online:

Braverman, L. E., & Cooper, D. S. (2013). Introduction to thyrotoxicosis. In L. E. Braverman & D. S. Cooper (Eds.), Werner & Ingbar’s the thyroid: a fundamental and clinical text (10th ed..). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health.

Saberi, M., & Utiger, R. D. (1974). Serum Thyroid Hormone and Thyrotropin concentrations during thyroxine and triiodothyronine therapy. The Journal of Clinical Endocrinology & Metabolism, 39(5), 923–927. https://doi.org/10.1210/jcem-39-5-923

Snyder, P. J., & Utiger, R. D. (1972). Inhibition of thyrotropin response to thyrotropin-releasing hormone by small quantities of thyroid hormones. Journal of Clinical Investigation, 51(8), 2077–2084. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC292364/

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Categories: Biomarkers, Graves' Disease, Thyrotoxicosis, TSH hormone

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