New clinical trial of Armour Thyroid is recruiting U.S. patients

Page 2

Page 1Page 2Page 3 (references)

Will the study acknowledge diverse patient response?

When considering a “conversion” of dose from LT4 to desiccated, hopefully the study will consider differences between patients’ causes of hypothyroidism, their thyroid gland status, and their antibody status, and unique TSH – T3 setpoints.

  • Midgley et al, 2015 has usefully illustrated the significant variation in response to LT4 monotherapy even among thyroidless patients. There are good converters of thyroid hormone, moderate converters, and poor converters.
  • The “dose conversion” of LT4 to desiccated thyroid for a “poor converter” is likely going to be very different from that of a “good converter” even at the exact same TSH. The study may discover they may need higher doses to achieve equal TSH.
Midgley et al, 2015. FT3 (A), FT4 (B) and TSH (C) levels in L-T4-treated patients stratified by disease and conversion efficiency. The disease entities were closely associated with categories of the thyroid volume. Red: poor converter of T4 hormone. Green: moderate converter. Blue: good converter. Carcinoma: Total thyroidectomy for thyroid cancer. AIT, autoimmune thyroiditis; Goitre, goitre post surgery for benign nodular thyroid disease. n = number of patients.
  • Graves, Atrophic Thyroiditis and Hashimoto’s thyroiditis patients can have antibodies that directly interfere with TSH regulation by the pituitary gland at the ultrashort feedback loop. The TSHR stimulating antibody can be active even post-thyroidectomy, artificially lowering TSH despite lower FT4, and those with TSHR blocking antibodies tend to have exaggerated and fluctuating TSH levels (I’m one of those patients, so I know). This is why people with TSHR antibodies can achieve remission or flip-flop between hypothyroid and hypER status over 10 years until some people’s glands shrivel up (Takasu et al, 2012). It is rare for studies to measure TSH-Receptor antibodies in hypothyroid patients, but yeah, we have them, too.
  • It is not impossible for a patient to have undiagnosed mild central hypothyroidism (impaired TSH secretion) in addition to primary hypothyroidism. When TSH secretion is abnormally lower, even by a small fraction, it can lead to underdose when doses are religiously adjusted to stay within the normal reference range. In addition, euthyroid T3 hormone dosing (even at higher doses of desiccated thyroid) can have a localized TSH-suppressive effect at the hypothalamus, an effect that shows up with TRH-TSH testing (Koutras et al, 1981).
  • New research is showing that even on LT4 monotherapy, a TSH mildly below reference and a FT3 higher than midpoint of reference is where true euthyroidism exists for some types of patients (Ito et al, 2012, 2017, 2019; Larisch et al, 2018; Hoermann et al, 2019). This is the finding for a population of atrophic thyroid patients after Graves’ radioiodine therapy or athyreotic patients post-thyroidectomy, but even Hashimoto’s patients can have utterly fibrosed and inactive thyroid tissue. Those with little to no thyroid gland tissue have the statistically largest TSH-T3 disjoint, since they cannot benefit from thyroid tissue’s ability to enhance conversion of T4 to T3 via the “TSH-T3 shunt”…

    What is the “TSH-T3 shunt”? (see Berberich et al, 2018.) Briefly, it’s the way that a thyroid gland acts as a TSH-regulated T3 optimizer. But in thyroid disease, we each have different amounts of functional thyroid tissue that can still convert hormones, and this changes our T4-T3 conversion rate as blood flows through the thyroid gland with various concentrations of TSH (or TSH receptor antibodies that mimic TSH). Thyroid tissue expresses both Deiodinase Type 1 and 2. You cannot judge by dosage alone how much remnant thyroid tissue a person has or how fibrosed or atrophied (dead) the thyroid gland has become. Such can be estimated by ultrasound with measurements of a thyroid’s dimensions and obtaining data on its echogenicity.
  • It would have been wiser to limit recruitment to patients with total thyroidectomies so that this “wild card” of active thyroid gland secretion of T4 and T3 — this significant variable of unknown potency — can be controlled.

Please try to divide us into cohorts by thyroid disease type and gland health.

Please express results as a range and publish a study that gives a vivid scatterplot graph showing where individual data points are.

A static “equivalency” of LT4 dosing to Armour Thyroid dosing is very unfair and unrealistic to the individual thyroid patient. An “average” when all thyroid patients, regardless of dose or conversion rate, are lumped together, is not representative of the unique metabolic challenges faced by each cohort.

Will they multi-dose?

Another challenge with this study regards multi-dosing several times a day.

This is a major controversy in T3-T4 combination clinical trials, with some people blaming the combination’s failure to achieve “superiority” over levothyroxine on the fact they were not dosing the T3 medication two or three times a day to even out patients’ Free T3 levels.

Dosing 1x a day not wise if the dose is larger than 120 mg/day (two grains), given that the content of 60 mg Armour is 9 mcg T3 and 38 mcg T4 according to the product information pdf, and there is a considerable short-term peak and valley in Free T3 after dosing T3.

If they do measure T3 concentrations, they will need to measure them outside of the volatile peak hours when waiting 20 minutes can yield a significantly different result.

The larger the NDT dose, the higher the FT3 peak will be, but it won’t last much longer over time.

If you dose in the morning, you could be hypothyroid by evening … if you’re riding on FT3 to sustain you because you can’t convert enough T4 locally in cells.

During a higher Peak FT3, some may have mildly higher heart rates and other fast acting metabolic responses.

When the peak FT3 is very high, it is likely that Deiodinase Type 3 will be triggered in tissues. D3 enzyme will increase the rate of T3 conversion to T2 and the rate of T4 conversion to Reverse T3, which means less hormone is converted to the active form T3 in cells.

The loss of T3 from cells due to local hormone inactivation in tissues is not as likely to be noticed in blood when you are resupplying T3 daily, but it can make a difference to various organs and tissues at the local level.

Symptoms may be confusingly both hypo and hyper if T3 and T4 levels are, either separately or combined, higher than the metabolic setpoint for an individual patient, the state that upregulates Deiodinase type 3. The three deiodinases can be imbalanced in a different ways in each tissue and organ, and T3 and T4 exchange with tissues at different rates over time, meaning some symptoms of local T3 loss show up earlier, some later.

How much is too much? Given that the healthy range for Free T3 is as narrow as 38% of reference range, you cannot predict where a person’s upper or lower boundary of their FT3 setpoint lies in relationship to statistical population reference ranges. There is no absolute FT3 target that fits everyone, just a general rule of thumb that the lower half of reference is where thyroid patients tend to suffer hypothyroidism. One has to safely creep up toward optimal levels in dose adjustments, not mistaking pituitary euthyroidism (statistically normal TSH) for generalized euthyroidism, as Yavuz and team wisely caution.

Science already knows what can happen when higher T3 thyroid hormone levels are insufficient for some organs but excessive for others. A contradictory symptomatic presentation has long been recognized in the syndrome called Resistance to Thyroid Hormone (RTH), in which “thyroid hormone deficiency and excess coexist” while the body requires abnormally higher thyroid hormone levels (Dumitrescu & Refetoff, 2013).

  • In a nutshell, RTH patients have a genetic insensitivity in one thyroid hormone receptor family, THRB, but not the other, THRA. Some tissues express primarily THRB, others THRA. They need more circulating T4 and/or T3 to activate their THRB receptors in brain while their THRA receptors in heart are overactivated. If the THRB receptors in the pituitary are affected, the TSH will not be suppressed by higher levels of thyroid hormone, but some genetic variants are pituitary specific and affect the TSH secretion, others generalized and affect multiple organs. The presentation varies from patient to patient and can be mild or severe.

Given that excessive transient Free T3 peaks can trigger deiodinase imbalances and weirdly contradictory symptoms like those seen in RTH, multi-dosing is a way to ensure adverse responses don’t occur during desiccated thyroid therapy trials.

High hopes and best wishes

Thyroid patients who have experience with desiccated thyroid therapy are eager to know what you discover through this clinical trial.

Not all clinical trials are successfully completed, either due to lack of participants or funding, or other unexpected challenges.

Not all results of trials are published. Sometimes the process of publication can be delayed during data analysis, scientific peer review, or editing processes.

We hope our article helps to recruit enough participants. Please do not hide or delay your findings. Publish them as soon as you can.

  • Tania S. Smith on behalf of Thyroid Patients Canada

Navigate pages

Leave a public reply here, on our website.

This site uses Akismet to reduce spam. Learn how your comment data is processed.