2018 study shows T3 in upper half of reference range relieves hypothyroid symptoms

This Sept. 2018 research article proved that thyroid patients’ continued hypothyroid symptoms are connected to Free T3 levels.(1)

Symptom relief for thyroid patients on the standard T4 monotherapy is found “in the upper half of the FT3 reference range.”

Symptoms had a limited and paradoxical relationship with TSH, and absolutely no relationship to a patient’s age, sex, or body mass index. Of course, TSH & FT4 were normalized. But that didn’t matter. It was all about upper-range Free T3.

The statistical correlation is very strong, patterns were clear.

There was very little likelihood of any placebo effect since a raised dose did not always result in freedom from hypothyroid symptoms.

METHODS

This was not based on a mere subjective survey of patients, but on objectively clinically scored symptoms reported by patients over 2309 doctor visits.

The study ran for an average of 63 months [5.25 years] on 319 athyreotic patients.

“Suggestive questions were avoided and no standardized questionnaire was used.”

“The documented complaints were then independently categorised by an endocrinologist who was not otherwise involved in the patient’s treatment.”

“The three symptom categories were

• hypothyroid symptoms (e. g. tiredness, fatigue, lack of energy, cold intolerance, weight gain),
• hyperthyroid symptoms (e. g. nervousness, irritability, restlessness, anxiety, rapid pulse, palpitations, trembling, heat intolerance, unwanted weight loss), or
• thyroid-unrelated symptoms (e. g. back pain).”

The study also excluded anyone who could have had lower Free T3 caused by non-thyroidal illnesses. Nobody’s levels were skewed by pregnancy.

According to the standard TSH-paradigm’s definition of hypothyroidism (which ignores Free T3 status) nobody qualified for hypothyroid status because nobody had a TSH above normal range or a FT4 below normal.

Patients with low risk for cancer recurrence were kept at a normalized TSH. Those who were at a high risk of cancer had their TSH suppressed. Their data analysis also looked at how these two cohorts differed.

The average LT4 dose was 150mcg/day, and the average weight-adjusted dose was 1.84 mcg / kg. This is normal for athyreotic patients.

During the study, patients’ doses were adjusted based on cancer therapy guidelines (suppressed or normalized TSH according to the patient’s category) and doses were also adjusted in response to patient complaints while the laboratory results for TSH and FT4 remained within these guidelines.

RESULTS

In general, patients were far more likely to complain of hypothyroid symptoms than hyper, even though TSH was therapeutically kept below range for a large portion of the patients.

“The rate of hypothyroid complaints per presentation was 6.5 % and that of hyperthyroid symptoms 2 %.”

On the other side of the spectrum, hyperthyroidism, no patients reported any hyperthyroid symptoms due to mere TSH suppression alone.

Symptoms only appeared when the FT3 was above 7.5 pmol/L, the point at which the miniscule number of hyperthyroid complaints occurred (only reported at 2% of all doctors’ appointments).

The extreme low end of TSH was not invariably correlated with relief of hypothyroid symptoms. It only correlated with symptom-free status when a suppressed TSH co-presented with FT3 above the midpoint of normal range.

Even past the point of TSH suppression below reference, FT3 continued to increase on average.

However, the average response across the entire cohort is very misleading.

• The lower the patient’s TSH went, the wider the FT3 data spread became.
• At a suppressed TSH, one patient could have high FT3 while another could have FT3 below reference.

For 31% of patients, even complete TSH suppression left them with FT3 below the reference range.  In other words, T4 monotherapy was unable to normalize their FT3.  In these patients, L-T4 dose escalation suppressed TSH but gave little benefit in FT3.

TREATED PATIENTS VS. HEALTHY CONTROLS

This study confirmed other studies that have proven that thyroid therapy grossly distorts the TSH-FT3 relationship.

TSH suppression means something completely different in treated thyroid patients than it does in patients who are not taking thyroid meds.  Therefore it is a false analogy to judge thyroid patients’ thyroid hormone sufficiency by the reference range of healthy controls.

The results in this study can be compared with an earlier study by the same lead researchers using the same assay kits and the same standard laboratory reference ranges. (2) In the earlier study, 399 healthy subjects’ values were analyzed to verify the manufacturer-recommended reference ranges for TSH. Their FT3 and FT4 were also measured.

The list below shows average values, [Interquartile range of values], (lab reference ranges), then healthy controls’ average values and the [Standard Deviation]:

• TSH 0.07 [0.01, 0.46] (0.4 to 4.0 mIU/l) — VS. Controls 1.6 [+/-  1.0]
• FT3 5.15 [4.60, 5.80] (3.1 to 6.8 pmol/l) — VS. Controls 5.1 [+/-  0.6]
• FT4 22.3 [19.6, 25.4] (10 to 23 pmol/l) — VS. Controls 14.3 [+/-  1.8]
• FT3 / FT4 ratio = 0.23 pmol/L. — VS. Controls 0.356 pmol/L

Here is what these results mean:

Treated patients

• An average FT3 at parity with controls means an average TSH 1.53 mIU/L lower than healthy controls.
• Patients’ Free T4 was on average 8 pmol/L higher than healthy controls. A difference of 8 pmol/L is 61.5% of the width of the entire FT4 reference range.
• To achieve the same average FT3 of 5.1, pmol/L as healthy controls, the athyreotic patients on L-T4 monotherapy had to have an average TSH well below reference range, 0.07.
• The patients’ TSH was obviously suppressed by a very high Free T4 near the top of reference, due to being treated with T4 hormone alone.

Healthy controls

One standard deviation away from the mean in both direction accounts for 68.2% of healthy people.

• Among this 68% of healthy people,
  • TSH values populated only 55% of its reference range
  • FT3 values populated only 32% of its reference range
  • FT4 varied populated only 27% of its reference range
• 68.2% of healthy people have a Free T3 between
  • 4.5 pmol/L, 37% of reference range and
  • 5.7 pmol/L, 70% of reference range.
• In healthy individuals the mean levels were
  • TSH = 33% higher than the low boundary of reference
  • FT4 = 33% higher ” “
  • FT3 = 54% higher ” “

We challenge ANY large study of ANY mode of thyroid therapy for athyreotic patients to achieve the mean values, ranges and ratios of healthy controls.

We don’t believe it is possible, but just try to prove us wrong.

IMPLICATIONS FOR FT3

Some might say these are “only symptoms,” but they are not imaginary. The statistical correlation with FT3 levels is very strong. They are signs of hypofunctioning organs and bodily systems.

FT3’s relationship with symptoms fits today’s understanding of central and peripheral thyroid hormone metabolism. It is only reasonable to believe that when the clinical presentation of hypothyroidism appears with lower Free T3 despite higher Free T4, it signifies that there is less T3 transport into peripheral tissues beyond the pituitary gland and less local T4-T3 conversion within those tissues.

Clearly, T4 monotherapy can fail a large portion of people with dead or missing thyroid glands.

How can an endocrinologist consider it okay to force up to 31% of post-thyroidectomy patients to live the rest of their lives with FT3 below reference along with continual hypothyroid symptoms?

Clearly, these compassionate researchers didn’t think it was okay to let patients languish. They ended up normalizing the average FT3 in their patient cohort, but they were unable to normalize FT3 for 1/3 of their patients.

IMPLICATIONS FOR TSH

Clearly, normal TSH is not an indicator thyroid hormone levels in treated patients.

The pituitary gland’s secretion of TSH is strongly biased and distorted by the thyroid therapy modality and the dose of hormone taken by the patient.

This means that policies about avoiding TSH suppression in therapy due to cardiovascular risk and bone health risk could be incorrect.

How far can these “Low TSH = Risk” studies be applied to this patient cohort? They rarely measure T3, which is the most important thyroid hormone.

They cannot distinguish between 3 types of thyroid patients in the low TSH category:

• LOW FT3 in spite of a suppressed TSH (up to 31% of athyreotic patients)
• HIGH FT3 that would be consistent with suppressed TSH
• MEAN FT3 of 5.1, that of a healthy person, along with suppressed TSH.

The majority of the TSH – health risk studies not even study patients without thyroid glands who are taking T4 monotherapy at high doses. Studies often exclude anyone with a thyroid diagnosis and anyone taking thyroid hormones.

OPTIMIZE T3. SET US FREE.

The fact is, life with a damaged, dead or missing thyroid gland changes things irreversibly so that the body can’t protect serum Free T3 levels anymore.

Giving oral thyroid hormones can never restore the normal TSH response — the TSH is clearly oversensitive to oral dosing of thyroid hormone.

The best compromise for health is NOT achieved by normalizing the TSH, but by optimizing Free T3 above the mid-point of reference.

Want to save money? Scrap the TSH test for treated patients and just measure Free T3.

REFERENCES

1.  Larisch, R., Midgley, J. E. M., Dietrich, J. W., & Hoermann, R. (2018). Symptomatic Relief is Related to Serum Free Triiodothyronine Concentrations during Follow-up in Levothyroxine-Treated Patients with Differentiated Thyroid Cancer. Experimental and Clinical Endocrinology & Diabetes, 126(09), 546–552. https://doi.org/10.1055/s-0043-125064

2. Larisch, R., Giacobino, A., Eckl, W., Wahl, H.-G., Midgley, J. E. M., & Hoermann, R. (2015). Reference range for thyrotropin. Post hoc assessment. Nuklearmedizin. Nuclear Medicine, 54(3), 112–117. https://doi.org/10.3413/Nukmed-0671-14-06