Review: Hoang’s 2013 conversion table for desiccated thyroid

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Solutions

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.

“Dose escalation had a stronger effect on suppressing TSH than raising FT3 concentrations, leaving 31 % of the presentations with FT3 concentrations still in the lower half of the reference range despite a suppressed TSH.”

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

Related posts

About LT4 and LT3 pharmaceutical equivalency (Synthroid and other LT4 brands to Cytomel and other LT3 brands)

In history

[Read the post]

In new thyroid science

(Celi et al, 2010, 2011, and Yavuz 2013)

[Read the post]

References

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

Celi, F. S., Zemskova, M., Linderman, J. D., Smith, S., Drinkard, B., Sachdev, V., Skarulis, M. C., Kozlosky, M., Csako, G., Costello, R., & Pucino, F. (2011). Metabolic effects of liothyronine therapy in hypothyroidism: A randomized, double-blind, crossover trial of liothyronine versus levothyroxine. The Journal of Clinical Endocrinology and Metabolism, 96(11), 3466–3474. https://doi.org/10.1210/jc.2011-1329

Green, W. L. (1968). Guidelines for the Treatment of Myxedema. Medical Clinics of North America, 52(2), 431–450. https://doi.org/10.1016/S0025-7125(16)32935-2

Hamilton, T. E., Davis, S., Onstad, L., & Kopecky, K. J. (2008). Thyrotropin Levels in a Population with No Clinical, Autoantibody, or Ultrasonographic Evidence of Thyroid Disease: Implications for the Diagnosis of Subclinical Hypothyroidism. The Journal of Clinical Endocrinology and Metabolism, 93(4), 1224–1230. https://doi.org/10.1210/jc.2006-2300

Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2019). Functional and Symptomatic Individuality in the Response to Levothyroxine Treatment. Frontiers in Endocrinology, 10. https://doi.org/10.3389/fendo.2019.00664

Ito, M., Miyauchi, A., Kang, S., Hisakado, M., Yoshioka, W., Ide, A., Kudo, T., Nishihara, E., Kihara, M., Ito, Y., Kobayashi, K., Miya, A., Fukata, S., Nakamura, H., & Amino, N. (2015). Effect of the presence of remnant thyroid tissue on the serum thyroid hormone balance in thyroidectomized patients. European Journal of Endocrinology, 173(3), 333–340. https://doi.org/10.1530/EJE-15-0138

Ito, M., Miyauchi, A., Morita, S., Kudo, T., Nishihara, E., Kihara, M., Takamura, Y., Ito, Y., Kobayashi, K., Miya, A., Kubota, S., & Amino, N. (2012). TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy. European Journal of Endocrinology, 167, 373–378. https://doi.org/DOI: 10.1530/EJE-11-1029

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

Ito, M., Miyauchi, A., Hisakado, M., Yoshioka, W., Kudo, T., Nishihara, E., Kihara, M., Ito, Y., Miya, A., Fukata, S., Nishikawa, M., & Nakamura, H. (2019). Thyroid function related symptoms during levothyroxine monotherapy in athyreotic patients. Endocrine Journal, 66(11). https://doi.org/10.1507/endocrj.EJ19-0094

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: Official Journal, German Society of Endocrinology [and] German Diabetes Association, 126(9), 546–552. https://doi.org/10.1055/s-0043-125064

McMillan, M., Rotenberg, K. S., Vora, K., Sterman, A. B., Thevathasan, L., Ryan, M. F., Mehra, M., & Sandulli, W. (2016). Comorbidities, Concomitant Medications, and Diet as Factors Affecting Levothyroxine Therapy: Results of the CONTROL Surveillance Project. Drugs in R&D, 16(1), 53–68. https://doi.org/10.1007/s40268-015-0116-6

Midgley, J. E. M., Larisch, R., Dietrich, J. W., & Hoermann, R. (2015). Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency. Endocrine Connections, 4(4), 196–205. https://doi.org/10.1530/EC-15-0056

Wiersinga, W. M., Duntas, L., Fadeyev, V., & Nygaard, B. (2012). 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism. European Thyroid Journal, 1(2). https://doi.org/10.1159/000339444

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

4 replies

  1. This conversion table is all wrong. Patients cannot have had Ft3 in upper quarter of range. I have seen hundreds of people on NDT. These doses are way too low.

    • Certainly, this is a flaw of both tables, the variation in individual response to both thyroid medications. Poor converters of T4 of need higher doses to get enough T3 out of their T4 from thyroid medication.

  2. Over the years I have come to think of the OLD conversion tables as having good and bad points.

    Whilst the issues of individuality apply to any purported conversion, it is obviously useful to have somewhere to start.

    The OLD table would tend to convert people onto a too low dose of desiccated thyroid – that is, it would tend to err on the side of overall safety. With adequate patient awareness and monitoring, that isn’t too major a problem. Even with a cast iron conversion factor, it might not be a bad idea to convert to a very slightly low dose of desiccated thyroid with the intention of adjusting very soon.

    When people convert from desiccated thyroid to levothyroxine, the tables would tend to overdose the patients. (There could be many reasons to convert back, not least when supplies of desiccated thyroid disappear.) This is, in my view, an important issue.

    My own, highly unscientific feeling, from reading many posts on forums over the years, 60 milligrams of desiccated thyroid often works out around 75 micrograms of levothyroxine.

    • Thanks for your comments. I heartily agree that safety should be achieved by gradually titrating the dose upwards from a lower level. This practice is recommended elsewhere in product monographs and guidelines.

      Conversion charts, on the other hand, are supposed to help us understand approximate equal metabolic potency once dose titration has been achieved.

      The most scientific approach to this table is to respect the wide variation among thyroid patients’ metabolic health. Provide a range of equivalency for one of the medications, i.e. 100 mcg of LT4 is equivalent to X to X of desiccated thyroid, or vice versa.

      Good converters — Some people certainly may require lower doses of both thyroid medications because they have a lot of functional thyroid tissue remaining, or they are highly efficient T4 converters even without any thyroid tissue left. Safety in these patients should be achieved by understanding how thyroid hormone levels and ratios reflect general T3 supply to all tissues. In a “good converter” on DTE, the FT3 level will be significantly higher than the FT4. When the FT3:FT4 ratio is high, the FT4 may need to fall low to safely compensate for a higher FT3. Arguably, such patients would be fine on LT4 monotherapy because they convert so well.

      Poor converters: In some patients, the loss of thyroid gland tissue can no longer compensate for an underlying inefficiency in thyroid hormone metabolism, whether genetic, or acquired from other health conditions or medications. These are the patients who fare very poorly on both medications unless TSH is permitted to fall in compensation.

      In poor converters, as dose rises, TSH falls before euthyroidism is achieved. This is because they achieve T3 sufficiency in the hypothalamus and pituitary gland before they achieve it in other tissues.

      To support this physiological principle, science has been revealing that the deiodinases that convert thyroid hormone function differently in different organs. The pituitary and hypothalamus convert using D1 and D2, but these enzymes behave differently there than elsewhere in the body. For example, D1 in the liver is regulated by activation of a liver enzyme receptor, LXRα (Sakane et al, 2017), which means FT3 contributions from the liver could be hindered while local T3 supplies are unaffected in the pituitary and hypothalamus. D2 enzyme in brown adipose tissue can be activated by a cold environment, which is different from D2 behavior in the pituitary and hypothalamus.

      For safety, testing both thyroid hormones during thyroid therapy correctly identifies people who are underdosed on both thyroid therapies within the current TSH paradigm.

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