Interpreting Free T3 and Free T4 in therapy

Hypothyroidism is a thyroid hormone insufficiency, so it’s only logical to measure the success of therapy by the goal: T4 and T3 thyroid hormone sufficiency.

Especially T3 sufficiency, the active hormone.

Lab tests like Free T3 and Free T4 can indicate “relative” T3 and T4 sufficiency in bloodstream … but one has to carefully interpret the results in light of a patient’s symptoms.

How do we determine “sufficiency”?

Not just anywhere within population-wide reference ranges.

Nope, when you look at the thyroid hormones, those reference ranges are pretty much only good for population statistics.

Thyroid reference ranges are not like reference ranges for vitamin D or blood glucose, which are statistically about the same for a large group of people (all men, or all women, or all pregnant women, people over age 70) as they are for an individual in that group.

Thyroid reference ranges are unique. They are way too broad to be applicable to a single individual. Research shows we each have an optimal or healthy “set point” for thyroid hormone levels that is about 50% narrower than the statistical “normal” reference range. (Fitzgerald & Bean, 2016 ; Hoermann et al, 2015)

• See “Individual thyroid ranges are 38-68% the size of the lab reference range“

Sadly, when Free T3 falls lower in chronic illness, TSH and T4 can still be “normal.”  Unfortunately, the statistics that create reference ranges are likely going to count a whole bunch of those sickly, low T3 levels as “normal” because they do occur in a sick person with a “normal TSH” and a “normal T4.” As a result, even our Free T3 “normal” reference range likely goes down too far into an unhealthy zone.

So, neither a normal TSH, nor a normal T4, not even a normal range T3 — those population statistics cannot tell you what’s “normal” for the patient named Bob, if he had a perfect thyroid and perfect health.

We must interpret with this in mind.

T3/T4 dose content vs. dose effect

Currently the literature on combination therapy and the critique of desiccated thyroid (DTE) is focusing too much on the ratios of T3 and T4 hormones in the pills and not enough on to the amounts and ratios in blood and peripheral tissues and their effects on the patient’s organs and tissues.

Give up on trying to approximate the ratio of T3 to T4 in the human thyroid gland or its secretion. All hormone therapy is artificial.

Thyroid hormones in the natural state are flexible and variable in their relationship. The pill contents matter a lot less than their effects on the individual human body — the resulting T3 and T4 blood levels and the T4 peripheral conversion potential.

Adjust the dosing ratios as needed until there is sufficient T3 supplied directly to the organs that depend on it in bloodstream. In relation to that T3 level in blood, the rest of their T3 can be supplied indirectly and peripherally via T4 conversion.

However, some patients with limited peripheral conversion may respond better with more T3 than T4 in bloodstream — more direct (T3) than indirect (T4) hormone entering the peripheral cells, thus less dependency on peripheral conversion.

For some patients who need T3 medication, the response may be better with desiccated thyroid extract (DTE) than for synthetic L-T3/T4 combination therapy.  Although liothyronine molecules are technically “bioidentical,” they are not configured the same way as triiodothyronine molecules, and DTE likely contains more T3 that is already bound to carrier proteins.

Free T3 and Free T4 in relationship

There is a lot of value in measuring Free T3 and Free T4, because we need to know approximately how much room (within a wide statistical range) we might have for dose adjustments for an individual.

We also need to interpret the ratios between the T3 and T4 hormones.

• If Free T3 is too far below Free T4 in their respective ranges, we may suspect a T4-T3 conversion problem, excess T4 converting to Reverse T3, or illness lowering the metabolic set-point.
• If Free T4 is high in reference range, if it’s keeping TSH too low, less of that T4 will become T3 in the body.  A low TSH can’t nudge T4-T3 conversion within peripheral cells and tissues like bones (TSH stimulates deiodinase type 2 activity).
• In healthy T3-based therapies (synthetic combination therapy or desiccated thyroid), when there is relatively less inactive T4, the body will require more active T3 to compensate for the T4 that would have become T3 later, within cells and tissues.

Read more about the implications of various T3:T4 ratios.

Free T3 and T4 in relation to signs and symptoms

Next, when interpreting these levels, we need to return to collecting relevant data from signs and symptoms.

Some signs and biomarkers, like the simple and cost-effective ankle reflex test, can indicate T3 sufficiency in peripheral tissues like no blood test can.

As for the time and energy involved, doctors do not have to do all the work. Relevant testing does not have to always occur in a medical facility.

Patients can be taught to monitor themselves when taking therapies that contain T3 hormone. No patient will enjoy the symptoms of true hyperthyroidism.

If patients truly want to get better, they will accept the inconvenience of taking a T3-containing medication more than once a day.  They will learn about thyroid hormone effects and listen to their bodies, keeping symptom diaries and tracking their doses and when they take them during the day until they find a system that works.

Someday, perhaps someone will develop a T3 blood level monitoring system, like blood sugar measuring devices for diabetics, but until that day, monitoring signs and symptoms will have to do.

If the patient makes a dosing mistake, because the T3 half life is so short, the mistake only affects them for a few hours during a single day. It will be unpleasant, so they won’t make that mistake again. The body can and does protect itself by binding and consuming a temporary excess T3 in bloodstream. Milk thistle herb can be taken to encourage quicker elimination of excess hormones through the liver.

To watch even for mild hyperthyroidism on average, basal metabolic rate and basal body temperature can easily be measured from day to day at home. T3 affects metabolic rate more noticeably the larger the T3 dose and the less a patient depends on gradual T4-T3 conversion.

Let’s bring symptom scores and checklists back into the doctor’s office. Get patients to submit symptom diaries. Yes, this is useful data. Patients hear their thyroid hormones speak to them day after day, week after week.

Each patient is unique. Some patients will feel symptoms first in their mental health, others in hair loss, still others in digestion or constipation — it depends on the systems in their body that are most vulnerable to T3 deficiency or excess.

This is how we optimize Free T3 levels, working together as doctor and patient.

This is also why we strongly advocate for Free T3 testing in thyroid therapy.