In another post, I’ve already covered the reasons why TSH is a poor indicator in L-T4 monotherapy (Synthroid, Levothyroxine)
Here, I’ll deal with another situation in which TSH is not indicative: low TSH in T3-based therapies such as
- desiccated thyroid (NDT / DTE)
- L-T4-T3 combination therapy.
Treating a patient by their TSH alone, especially in these therapies, will very likely lead to the suboptimal T3 level depicted on the right-hand side of this image:
These hypothetical examples are based on research studies as well as real patient experience. Each of these 3 examples depicts an individual person’s potential configuration of Free T3, Free T4 and TSH. For more information on “Non-thyroidal illness,” which can be experienced by people with normal thyroid glands as well as thyroid patients, see “Rationale: Low T3 Syndrome, part 1.”
The gray area of “optimal Free T3” in the image is an estimate based on many patients’ collective experience with desiccated thyroid therapy. This gray area is based on research showing that each healthy individual has a T3 range that is about 50% as wide as the reference range (see “Rationale: Reference ranges.”) For a thyroid patient who cannot easily protect their T3 levels over time, it’s best to aim for an even narrower optimal range for maintenance.
In all these states, a low TSH does not indicate true “hyperthyroid” status. In fact, they are the opposite. They are all hypothyroid. They are all deficient in the only thyroid hormone that has the direct effect on metabolism and organ function (T3).
TSH alone can’t define hyper- or hypothyroid status
Biologically, three main problems make it impossible for TSH alone to define true hypothyroidism, especially in thyroid therapy:
- TSH does not enter thyroid hormone receptors. Only T3 can enter them and have important genomic activity there.
- TSH does not directly correlate with T3 hormone levels, even in the healthy HPT axis.
- TSH operates differently under the artificial conditions of thyroid hormone therapy.
Doctors are told that a low TSH puts a patient at “risk” of osteoporosis, but in fact TSH plays an indirect role in bone cells. (We address this fear in a separate post, “Fear of Low TSH causing osteoporosis“). TSH encourages more T4-T3 conversion in bone cells, but TSH cannot make up for a deficiency in T3 in bloodstream for the organs that depend more on that source of T3. The role of TSH is insignificant in “Low T3 syndrome” when T4 and T3 thyroid hormone “inactivation” outpaces its conversion.
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. See Klein & Danzi, 2007 in PDF.
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.
Dosing by the TSH test is a sure way to make T3-based therapy fail. It can make it impossible to raise T3 and T4 levels sufficiently in patients with lower thyroid function.
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.
The height of the peak is based on 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 since the 1950s. You will find reports people surviving in good health on large doses of T3 hormone alone, without any T4 in circulation because of TSH suppression and/or the lack of a thyroid gland.
Of course their Free T3 levels pulsed and faded. Did they have a heart attack because of it? Find out by reading the history of T3-based therapy in articles before the TSH test overruled the definition of hyperthyroidism. Although some adverse cardio-metabolic effects on T3-based therapies were reported because of dosing errors, the fact that such effects were reported likely meant overdoses were not maintained over the long term.
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.
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, aim for the middle or upper normal range of Free T3.
You’ll know when the patient is optimal on their therapy when their sufficient T3 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.
Read more: Rationale: Low TSH vs. true hyperthyroidism