Letter on diagnosis published on British Medical Journal website

Subclinical-Further-beyond-reach-BMJToday, the British Medical Journal’s website published my “rapid response” letter:

How can truly hypothyroid patients be accurately diagnosed within the enlarged subclinical category?

Link to full text: https://www.bmj.com/content/365/bmj.l2006/rr-6

It is a response to the new guidelines for subclinical hypothyroidism:

Bekkering, G. E., Agoritsas, T., Lytvyn, L., Heen, A. F., Feller, M., Moutzouri, E., … Vermandere, M. (2019). Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ, 365, l2006. https://doi.org/10.1136/bmj.l2006


“My main concern with the new guidelines is for the health of patients who are truly hypothyroid despite TSH and T4 levels that place them within the now broader subclinical hypothyroidism category.”

“I believe ‘false-negatives’ will genuinely suffer without appropriate therapy if they are over 30 and not pregnant. A person is a false negative when they are denied the diagnosis and therapy for overt hypothyroidism because they are miscategorized as subclinical.”


“If the TSH-T4 paradigm contributed to overtreatment and ineffective therapy, and if this paradigm resulted in many false positives, then how is it helpful to expand the gray area created by this paradigm, use it to make the subclinical category even wider, and then forbid therapy within that category? This creates a larger gray area for false negatives.”

“I propose a better way forward: Acknowledge the flaws of the TSH-T4 diagnosis paradigm, and then take steps to improve thyroid diagnosis. Surely medicine wishes to prevent harm. Identify the genuinely hypothyroid patients in this category.”


“The symptoms of hypothyroidism are commonly dismissed by logical fallacies. The reasoning is that because the symptoms of hypothyroidism _can_ be caused by other health conditions, they _are_ caused by other health conditions, especially if the TSH and T4 levels persuade. But symptoms are the natural physiological effects of T3 hormone insufficiency, not the direct effects of TSH or T4. To say that all the classic hypothyroid symptoms are ‘nonspecific’ to hypothyroidism leaves no symptoms that are specific to hypothyroidism.”

“The guidelines in Box 3 state that ‘there is no clear evidence on how to attribute symptoms to SCH reliably, even with severe symptoms’ — this is not true.”


“Many relevant tests have been buried and forgotten by a medical paradigm that claimed TSH and T4 testing was enough – and this very paradigm led to the charge of ‘ineffective’ overtreatment of healthy patients within the vague subclinical category.”


  • Tania S. Smith


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2. Andersen, S., Bruun, N. H., Pedersen, K. M., & Laurberg, P. (2003). Biologic Variation is Important for Interpretation of Thyroid Function Tests. Thyroid, 13(11), 1069–1078. https://doi.org/10.1089/105072503770867237

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6. Chatzitomaris, A., Hoermann, R., Midgley, J. E., Hering, S., Urban, A., Dietrich, B., … Dietrich, J. W. (2017). Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00163

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9. Roelfsema, F., & Veldhuis, J. D. (2013). Thyrotropin Secretion Patterns in Health and Disease. Endocrine Reviews, 34(5), 619–657. https://doi.org/10.1210/er.2012-1076

10. Zulewski, H., Müller, B., Exer, P., Miserez, A. R., & Staub, J. J. (1997). Estimation of tissue hypothyroidism by a new clinical score: evaluation of patients with various grades of hypothyroidism and controls. The Journal of Clinical Endocrinology and Metabolism, 82(3), 771–776. https://doi.org/10.1210/jcem.82.3.3810

11. Meier, C., Trittibach, P., Guglielmetti, M., Staub, J.-J., & Müller, B. (2003). Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism in patients with overt primary thyroid failure: cross sectional survey. BMJ, 326(7384), 311–312. https://doi.org/10.1136/bmj.326.7384.311

12. Kalra, S., Khandelwal, S. K., & Goyal, A. (2011). Clinical scoring scales in thyroidology: A compendium. Indian Journal of Endocrinology and Metabolism, 15(Suppl2), S89–S94. https://doi.org/10.4103/2230-8210.83332

13. Dietrich, J. W., Landgrafe, G., & Fotiadou, E. H. (2012). TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis. Journal of Thyroid Research, 2012. https://doi.org/10.1155/2012/351864

14. Dietrich, J., Fischer, M., Jauch, J., Pantke, E., Gärtner, R., & Pickardt, C. (1999). SPINA-THYR: A novel systems theoretic approach to determine the secretion capacity of the thyroid gland. EFIM-2, 10(5 (Suppl 1)), S34.

15. Dietrich, J. W., Landgrafe-Mende, G., Wiora, E., Chatzitomaris, A., Klein, H. H., Midgley, J. E. M., & Hoermann, R. (2016). Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Frontiers in Endocrinology, 7. https://doi.org/10.3389/fendo.2016.00057

16. Ferrannini, E., Iervasi, G., Cobb, J., Ndreu, R., & Nannipieri, M. (2017). Insulin resistance and normal thyroid hormone levels: prospective study and metabolomic analysis. American Journal of Physiology-Endocrinology and Metabolism, 312(5), E429–E436. https://doi.org/10.1152/ajpendo.00464.2016

Competing interests: No competing interests

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