Choosing Wisely chooses not to hear thyroid patient’s research presentation

Our thyroid patient campaign’s researcher submitted a proposal to speak at the Choosing Wisely national conference in Montreal in May 2019.

A second thyroid patient was willing to fund the researcher’s trip from Western Canada.

A third thyroid patient put the researcher in contact with a thyroid doctor who was willing to support such educational efforts.

We were all waiting to hear whether Choosing Wisely would pick up the gauntlet.

Apparently they believe they are Choosing Wisely by saying no.

Message received February 21, 2019: “Unfortunately, your abstract was not selected for presentation at the National Meeting.”

THE REJECTED ABSTRACT

This is the proposal sent to this organization that is actively promoting the stance that Free T3 and Free T4 testing is unnecessary in hypothyroidism.

TITLE: Recent research on Free T3 and Free T4 testing in hypothyroid therapy

The goal of this presentation is to hear from a well-researched thyroid patient about the scientific literature 2013-2018 that supports the role of Free T3 and Free T4 blood tests in the monitoring of hypothyroid therapy, offering a counterbalance to current guidelines that consider them unnecessary tests.

Since the publication of the often cited 2012 American Thyroid Association and AACE’s Clinical Practice Guidelines for Hypothyroidism and the ATA’s more in-depth Guidelines for the Treatment of Hypothyroidism in 2014, clinical and laboratory studies as well as research reviews have questioned the dictum that only TSH should be used in the monitoring of hypothyroidism.

There is now a basis for a robust challenge of the hypothesis that the HPT axis behaves the same way in thyroid therapy as it does outside of hypothyroid therapy. Clinical studies have shown a very different pituitary TSH response to free hormone levels than that which applies in the healthy population; in fact, a TSH-T3 relationship disjoint exists under hormone therapy and is exaggerated in patients with less thyroid gland tissue.

Studies of patient symptoms have shown that the mean Free T3 level in healthy controls, approximately 5 pmol/L or greater, is the region where patients experience considerable symptomatic relief, proving that the significantly lowered T3:T4 ratio caused by L-T4 monotherapy has been incorrectly dismissed.

Therefore, there is scientific justification for the relaxation of current initiatives that aim to drastically reduce Free T3 and Free T4 testing in monitoring hypothyroid therapy.

20-item bibliography on request.”

There was no room within the 250-word abstract submission form to insert the bibliography, but here it is:

Bibliography

Abdalla, S. M., & Bianco, A. C. (2014). Defending plasma T3 is a biological priority. Clinical Endocrinology, 81(5), 633–641. https://doi.org/10.1111/cen.12538

Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I. L., Mechanick, J. I., … Woeber, K. A. (2012). Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocrine Practice, 18(6), 988–1028. https://doi.org/10.4158/EP12280.GL

Gereben, B., McAninch, E. A., Ribeiro, M. O., & Bianco, A. C. (2015). Scope and limitations of iodothyronine deiodinases in hypothyroidism. Nature Reviews. Endocrinology, 11(11), 642–652. https://doi.org/10.1038/nrendo.2015.155

Hoermann, R., Midgley, J. E. M., Dietrich, J. W., & Larisch, R. (2017). Dual control of pituitary thyroid stimulating hormone secretion by thyroxine and triiodothyronine in athyreotic patients. Therapeutic Advances in Endocrinology and Metabolism, 8(6), 83–95. https://doi.org/10.1177/2042018817716401

Hoermann, R., Midgley, J. E. M., Giacobino, A., Eckl, W. A., Wahl, H. G., Dietrich, J. W., & Larisch, R. (2014). Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment. Clinical Endocrinology, 81(6), 907–915. https://doi.org/10.1111/cen.12527

Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2013). Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? European Journal of Endocrinology, 168(2), 271–280. https://doi.org/10.1530/EJE-12-0819

Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2015). Integration of Peripheral and Glandular Regulation of Triiodothyronine Production by Thyrotropin in Untreated and Thyroxine-Treated Subjects. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, 47(9), 674–680. https://doi.org/10.1055/s-0034-1398616

Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2017). Recent advances in thyroid hormone regulation: Toward a new paradigm for optimal diagnosis and treatment. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00364

Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2018). Lessons from Randomised Clinical Trials for Triiodothyronine Treatment of Hypothyroidism: Have They Achieved Their Objectives? Journal of Thyroid Research, Article ID 3239197. https://doi.org/10.1155/2018/3239197

Ito, M., Miyauchi, A., Hisakado, M., Yoshioka, W., Ide, A., Kudo, T., … 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

Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., … Sawka, A. M. (2014). Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid, 24(12), 1670–1751. https://doi.org/10.1089/thy.2014.0028

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

McAninch, E. A., Rajan, K. B., Miller, C. H., & Bianco, A. C. (2018). Systemic Thyroid Hormone Status During Levothyroxine Therapy In Hypothyroidism: A Systematic Review and Meta-Analysis. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/jc.2018-01361

*Medici, B. B., la Cour, J. L., Michaelsson, L. F., Faber, J. O., & Nygaard, B. (2017). Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms. European Thyroid Journal, 6(2), 89–93. https://doi.org/10.1159/000454878 [*Note: I acknowledge this study’s strengths but critique its methods and conclusions using points from Hoermann, 2018 “Lessons”]

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

Park, E., Jung, J., Araki, O., Tsunekawa, K., Park, S. Y., Kim, J., … Lee, S. (2018). Concurrent TSHR mutations and DIO2 T92A polymorphism result in abnormal thyroid hormone metabolism. Scientific Reports, 8. https://doi.org/10.1038/s41598-018-28480-0

Peterson, S. J., McAninch, E. A., & Bianco, A. C. (2016). Is a Normal TSH Synonymous With “Euthyroidism” in Levothyroxine Monotherapy? The Journal of Clinical Endocrinology & Metabolism, 101(12), 4964–4973. https://doi.org/10.1210/jc.2016-2660
Strich, D., Karavani, G., Edri, S., & Gillis, D. (2016). TSH enhancement of FT4 to FT3 conversion is age dependent. European Journal of Endocrinology, 175(1), 49–54. https://doi.org/10.1530/EJE-16-0007

Werneck de Castro, J. P., Fonseca, T. L., Ueta, C. B., & McAninch, E. A. (2015). Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine. Journal of Clinical Investigation, 125(2), 769–781. https://doi.org/10.1172/JCI77588

Wiersinga, W. M. (2014). Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism. Nature Reviews Endocrinology, 10(3), 164–174. https://doi.org/10.1038/nrendo.2013.258