This is another great new article that points the way to a better way of thyroid treatment, which is more focused on relieving patient symptoms.
The article shows that the massive flaws in the previous research that has concluded T4/T3 therapy offers no clear benefit.
It points out the many flaws in relying on TSH and other lab tests alone as a means of assessing whether thyroid patients are adequately treated. It concludes with reference to the increasing rate of patient complaints about the non-relief of symptoms under the current flawed paradigm of lab test focused treatment.
I asked one of the co-authors for a summary of the article. Here are John Midgley’s own words on it:
Yes it has a year since first submitted. A long haul indeed but got there in the end.
This paper describes the history of thyroid function testing and therapy. It shows how the original therapeutic use of desiccated thyroid extract (DTE) was superseded by T4 monotherapy. It demonstrates that there was no formal clinical trial to compare effectiveness at the time. The principal reason was the inconsistency of DTE content at the time of change. However, nowadays DTE is carefully controlled by accepted chemical/physical methods. There has been no trial comparing DTE and T4 until about 2013.
The first milestones in the detection of dysfunction and therapy control were the development of tests to measure first total T4 and T3, and an initially insensitive TSH followed 15 years later by free T4 (FT4) and free T3 (FT3) tests + a sensitive TSH which could simultaneously detect hypo and hyperthyroidism. Historically Total T3 / FT3 was only used for diagnosing hyperthyroidism, for which it is still used today. Total T4 / T4 was found to be unsatisfactory for controlling T4 monotherapy because often the Total T4 or FT4 was above the healthy reference range. Sensitive TSH was found to be far more sensitive in detecting primary hypo and hyperthyroidism.
However, because the simple idea took hold that a lost thyroid meant lost T4 which could be fully substituted by oral hormone without further complication, the use of TSH as a therapy control was extended to patients on T4. We now know this is incorrect.
The thyroid makes both T4 and T3 so that the T3 in the body comes from a combination of direct thyroid production and body T4 conversion to T3. If the thyroid is lost, the whole system is severely altered.
In some cases, T4 only therapy can not make up for the T4 + T3 the thyroid originally made so that no matter how much T4 is given, the body’s conversion cannot make up for the T3 directly made by the working gland. It is these patients who need T3 in some form direct as oral therapy.
Finally, we all have our unique healthy combination of TSH, FT4 and FT3. They together define our health state and cannot be separated. Classical statistical analysis has in fact separated the parameters when studying a population. This is called univariate statistics. However, to get the proper picture, bivariate or trivariate analysis is need to keep the three parameters together for an individual in any group. This has implications for the value of TSH as a satisfactory control of therapy.
Finally, the results from randomised clinical trials, as to the efficacy and suitability of combined T4/T3 therapy, are severely compromised by including all patients, whether satisfied or dissatisfied, with T4 monotherapy in the analysis. The significant minority of patients that prefer combination therapy get swamped out and lost. This is an example of a statistical error called Simpson’s paradox. All trials so far fall under this problem and are therefore of no use. We provide ways to avoid this problem in future trials.
In short, therefore, the use of TSH in monitoring thyroid hormone therapy is highly unsatisfactory and should be replaced by triple FT4/FT3/TSH measurement + the presentation symptoms of the patient (which should have a primary role). Unthinking automatic biochemical definition of treatment success independent of the patient must cease, i.e. the laboratory test result focus must cease. Individuality is the decision-maker for optimum therapeutic outcomes.
Note: The loss of the thyroid in the above summary includes both thyroidectomy and Hashimoto’s thyroiditis, which destroys thyroid tissue.
Here’s the article information:
“Time for a reassessment of the treatment of hypothyroidism”
John E. M. Midgley, Anthony D. Toft, Rolf Larisch, Johannes W. Dietrich & Rudolf Hoermann.
BMC Endocrine Disorders volume 19, Article number: 37 (2019)