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These are the implications of the strengths and flaws in Hoang et al’s 2013 study.
1. Fix the old “US Pharmacopeia” tables.
Here is the old version and recommended update once again.
Desiccated thyroid product monographs in the United States and Canada still include these tables 7 years since Hoang’s study was published with a correction.
Why? Because they are still in the USP standards.
Someone with moral courage must submit a revision! Fix them.
How could the USP’s old tables be based on better evidence than the only double-blind clinical trial ever conducted on real thyroid patients using current preparations of desiccated thyroid and brand-name levothyroxine?
The old tables give a ratio that will lead to underdose on DTE.
Why is this a concern if so few patients require DTE therapy?
Because we have limited options for thyroid therapy, unlike diabetes therapy.
A diverse population of hypothyroid patients needs all three pharmaceutical options.
Patients who struggle with LT4 monotherapy and sysnthetic T4-T3 combinations are left with the third safe, valid option that was historically the only option—desiccated thyroid.
2. Question the assumption that we are all “average” thyroid patients.
These tables are not suited to achieve euthyroidism in patients who have little to no remaining functional thyroid tissue and who therefore differ in their T4-T3 conversion ability:
- Patients after a total thyroidectomy
- Patients with fully atrophied thyroid glands due to atrophic thyroiditis
- Patients with fully fibrosed thyroid glands due to Hashimoto’s thyroiditis
3. Question the assumption of TSH-based euthyroidism.
In this enlightened era, research evidence should trump tradition and opinion.
We have now had many clinical studies using multiple biochemical markers of tissue T3 status that go well beyond TSH. Yet even such rigorous studies seem to be afraid of letting go of opinion as guide and judge.
They still tend to idolize TSH as the only guide to titration and the final judge of euthyroidism.
Only the bravest of evidence-rich thyroid researchers such as Celi, Yavuz, Ito, Hoermann, Larisch, and Midgley have dared to question the validity of TSH—mere pituitary euthyroidism—as a sign of the entire body’s euthyroid status.
These scientists would without question agree that a TSH of 0.5 to 3.0 is not euthyroid for all thyroid patients on LT4 monotherapy, especially patients who lack thyroid tissue and who have thyroid metabolic handicaps.
Such patients are often not truly euthyroid until TSH is low or suppressed.
The fall of TSH naturally occurs in many such patients before Free T3 levels achieve true clinical euthyroidism for the individual. The FT3 needed to remove hypothyroid symptoms appears to be around mid-reference range in LT4 monotherapy. (Larisch et al, 2018; Hoermann et al, 2019).
Larisch’s study admitted that in about 1/3 of the patients, this level of FT3, the mean found in healthy controls, could not be achieved.
Larisch and team suggest these may be patients who fare better on therapies including T3 hormone.
Larisch recommends that the TSH reference boundary must not be idolized at the expense of health outcomes:
“In any event, a highly individualized approach is required, in view of a considerable biochemical and symptomatic variation in the response to LT4 treatment displayed in this study. Patients and doctors may have to experiment with dosing for optimum symptom control, and cannot simply rely on a TSH target within the reference range of a healthy population.”
(As for low-TSH risk studies, there is still no conclusive evidence that low TSH alone can “cause” osteoporosis or other diseases. Most association studies do not correlate health outcomes with FT3:FT4 ratios or FT3 tertiles.)
In Hoang’s study, TSH was the idol, and it prevented both therapies from achieving more than modest success “on average.”
4. Do better comparative clinical trials.
Trials like these are deeply flawed in their methodology and their premises, in ways that the ATA’s own review (Jonklaas et al, 2014) neglects to mention.
If medicine truly cares about the euthyroid status of diverse individuals on any and all thyroid therapy modality, fix the mistakes and learn more.
There is no such thing as one thyroid pharmaceutical that is superior to the other.
There are only pharmaceuticals and combinations that are better or worse for an individual patient.
It is not reasonable to treat unique individuals like the aggregate “average” patients and assume they will achieve “average” outcomes.
The purpose of clinical trials should not be to pursue an average level of “superiority,” since all this does is play a petty game of thyroid pharmaceutical prejudice that has closed minds since the 1980s.
The goal should be to support excellence in thyroid therapy for the sake of individuals’ health.
5. Make conversion tables with ranges.
Thyroid hormone homeostasis is about ranges, not fixed ratios.
There is no such thing as a single euthyroid TSH level, such as 1.5 mU/L, for all individuals. There is a range.
There is no such thing as a single optimal Free T3 or Free T4 level, such as 50% of reference range, even in untreated, healthy individuals. There is a range.
Therefore, why must we give the impression that there is a single dose of DTE / Desiccated thyroid that is metabolically equivalent to a single dose of LT4 levothyroxine?
We have fallen into a trap of reductivism and oversimplification that will cost time, money and health in the long run.
The older tables had more clinically accurate conversion estimates given as ranges.
Selenkow & Rose: 65 mg Armour = 100-125 mcg.
Green: 60 mg DTE = 120-180 mg
About LT4 and LT3 pharmaceutical equivalency (Synthroid and other LT4 brands to Cytomel and other LT3 brands)
In new thyroid science
(Celi et al, 2010, 2011, and Yavuz 2013)
AbbVie (2018). Armour® Thyroid (thyroid tablets, USP). https://media.allergan.com/actavis/actavis/media/allergan-pdf-documents/product-prescribing/06-2018-Armour-Thyroid-PI-final.pdf
Biondi, B., & Wartofsky, L. (2014). Treatment with thyroid hormone. Endocrine Reviews, 35(3), 433. https://doi.org/doi: 10.1210/er.2013-1083
Celi, F. S., Zemskova, M., Linderman, J. D., Babar, N. I., Skarulis, M. C., Csako, G., Wesley, R., Costello, R., Penzak, S. R., & Pucino, F. (2010). The pharmacodynamic equivalence of levothyroxine and liothyronine. A randomized, double blind, cross-over study in thyroidectomized patients. Clinical Endocrinology, 72(5), 709–715. https://doi.org/10.1111/j.1365-2265.2009.03700.x
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Ito, M., Kawasaki, M., Danno, H., Kohsaka, K., Nakamura, T., Hisakado, M., Yoshioka, W., Kasahara, T., Kudo, T., Nishihara, E., Fukata, S., Nishikawa, M., Nakamura, H., & Miyauchi, A. (2019). Serum Thyroid Hormone Balance in Levothyroxine Monotherapy-Treated Patients with Atrophic Thyroid After Radioiodine Treatment for Graves’ Disease. Thyroid: Official Journal of the American Thyroid Association. https://doi.org/10.1089/thy.2019.0135
Ito, M., Miyauchi, A., Hisakado, M., Yoshioka, W., Ide, A., Kudo, T., Nishihara, E., Kihara, M., Ito, Y., Kobayashi, K., Miya, A., Fukata, S., Nishikawa, M., Nakamura, H., & Amino, N. (2017). Biochemical Markers Reflecting Thyroid Function in Athyreotic Patients on Levothyroxine Monotherapy. Thyroid, 27(4), 484–490. https://doi.org/10.1089/thy.2016.0426
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Yavuz, S., Linderman, J. D., Smith, S., Zhao, X., Pucino, F., & Celi, F. S. (2013). The Dynamic Pituitary Response to Escalating-Dose TRH Stimulation Test in Hypothyroid Patients Treated With Liothyronine or Levothyroxine Replacement Therapy. The Journal of Clinical Endocrinology & Metabolism, 98(5), E862–E866. https://doi.org/10.1210/jc.2012-4196
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Categories: NDT / Desiccated thyroid