Treating T3 Deficiency (Part 6) Why T4 Thyroxine Therapy does not Improve Symptoms and Why TSH Suppression does NOT Result in Harm
Why T4 Thyroxine Therapy does not Improve Symptoms and Why TSH Suppression does NOT Result in Harm
On Day 1 of the Part I BHRT Workshop Series, I introduced the concept that “Association Does Not Prove Causation (ADNPC).” Every course subsequent to Part I, I have to reintroduce the concept as most clinicians understand the concept but fail to apply the principles when reading and interpreting studies. And this could not be more important when interpreting thyroid studies and expert opinions (which are Grade D evidence). So, here we go again.
In Treating T3 Deficiency (Part 4), I started with papers that concluded that T4-alone was not efficacious and did not improve symptoms. In fact, some authors suggested harm with thyroid use. Often, they stated that hypothyroidism was being over treated. However, I went on to review why T4-alone was not efficacious as it did not raise T3 levels which the endocrine world cannot conceptualize. Further dive into the studies demonstrated that adding T3 to T4 resulted in improvement in symptoms and efficacy. So, T4 can work if it is prescribed along with T3 but not as T4-alone.
In Treating T3 Deficiency (Part 3), I presented papers demonstrating that only when T3 is added to T4 do we experience weight loss. Treating T3 Deficiency (Part 4) also ended with papers demonstrating the efficacy of reducing CIMT and atherosclerosis with adequate thyroid administration. This usually occurs with only a sufficient dose that results in weight loss, which in turn lowers lipids which then results in a decrease in CIMT.
Why would anyone not want that?
Well, the AACE evidently does not, based on their current recommendations. I concluded the course with studies demonstrating thyroid hormone being beneficial in protecting against CVD- via the decrease in CIMT in multiple studies. Know any cardiologists that utilize thyroid to reverse plaque?
In Treating T3 Deficiency (Part 5), I reviewed the benefits of thyroid hormone in reducing IR, diabetes, and CVD. Low thyroid function, but still within the normal range, adversely affects metabolism and development of IR and diabetes. The higher the thyroid function (within the range of normal), the better the metabolism, weight loss, and CVD protection. The last section demonstrated the importance and benefit of thyroid hormone, particularly T3, in weight reduction and CVD risk factors. This segment then segues into the benefit of thyroid hormone in reducing insulin resistance that reverses NAFLD.
What is the FDA Approved Medicine to Treat and Reverse NAFLD?
In Treating T3 Deficiency Part 6, I will present studies that are opinion papers of the harm of thyroid hormone and all the reasons not to use thyroid hormone. A physician once explained to me that before one goes to battle, it is best to know the enemy first. Therefore, I will present current thinking and opinions as to why the use of thyroid hormone is to be avoided due to the harm demonstrated in various studies (supposedly). Unfortunately, the supposed harm is quoted and extrapolated from studies of patients with Graves’ disease. The harm of Graves’ disease should not be extrapolated to the use of exogenous thyroid administration, but they do and most authors and Endocrinologists do not understand the difference. The authors also suggest that thyroid hormone should not be used because it simply does not work as proved in their studies. They remain oblivious to all the papers presented in the thyroid webinars that simply adding T3, or DTE, suddenly makes the thyroid hormone efficacious. Nevertheless, the authors remain steadfast in suggesting that the T4 thyroxine should be stopped because symptoms do not improve on T4 alone.
Three very similar papers all demonstrate that thyroxine does not improve symptoms of hypothyroidism and therefore should not be used, particularly in seniors > 65 years of age. This segment ends with a paper from JCEM 2020 demonstrating that thyroxine can suppress T3 levels thereby proving why T4 does not improve symptoms in the JAMA and NEJM studies. Their solution is to simply add T3 which they proved does improve symptoms. Nevertheless, when big papers appear in big journals, the overall theme is to not use thyroid hormone and admonition that it could be harmful. The only resistance that is stronger than thyroid resistance or insulin resistance is physician resistance.
Further adding fuel to the fire, several papers suggest that too much thyroid is harmful, which is why PMDs express concern with suppressed TSH levels and our use of thyroid hormone. The first paper reviews the harm of high thyroid hormone levels and the increased risk of sudden cardiac death. “Thyroid hormone is more toxic than what we thought.” “The heart is working too hard because of high thyroid hormone.” Authors failed to appreciate that the harm was only seen in high baseline levels of thyroid hormone in patients with Graves’ disease. ADNPC. A second paper reviews the inappropriate use of thyroid hormone to treat thyroid nodules, a common occurrence. The authors claim harm of this iatrogenic hyperthyroidism that leads to an increased risk of cardiac and skeletal risks, so, don’t use it! The authors also went on to discuss the inappropriate use of thyroid hormone for weight loss, depression and fatigue.
Transitioning, a paper addresses that TSH suppression (biochemical hyperthyroidism) shows no harm in scientific studies. High levels are associated with harm, but we don’t see that harm with high dose exogenous administration. Again, the first authors can’t see the forest for the trees (ADNPC). Evidence is lacking for any adverse clinical impact that is significant even when the TSH is suppressed with exogenous replacement. Once we read papers that thyroid hormone is harmful, that negative harm sticks in our brain as a strong confirmation bias against the use of thyroid hormone.
Subclinical Hypothyroidism and Hyperthyroidism, Harms and Benefits
Next, we will review the impact of subclinical hypothyroidism and hyperthyroidism, harms and benefits. Unfortunately, these are association studies, but nevertheless lead us to understand why our endocrine colleagues fear TSH suppression but seem to ignore the harm of subclinical hypothyroidism. This gives us better appreciation for why our colleagues fear thyroid hormone and are afraid to prescribe it, yet they ignore the benefit of optimizing T3. Patients appear to feel the best when their TSH is 0.1 and feel the worst when their TSH is > 4.0.
Finally, I put thyroid replacement into perspective with a study demonstrating that optimal T3 levels can only be attained with very high dose T4 administration to suppress TSH to zero. Even then T3 levels do not return to pre-thyroid surgery levels due to loss of T3 by thyroid gland removal. Despite super suppression of TSH, T3 levels are not therapeutic to improve thyroid function or symptoms despite over-aggressive T4 administration. One would not realize this if Free T3 levels were not measured. Of course, AACE states that Free T3 is not a good test and should not be measured despite medical literature to the contrary. Despite serum T4 levels being markedly increased and TSH levels markedly decreased, the Free T3 levels still remained “significantly decreased” thereby accounting for the lack of improvement in hypothyroid symptoms even with high dose T4 replacement.
Hopefully, Treating T3 Deficiency Part 6 will better explain why T4 thyroxine therapy does not improve symptoms and why TSH suppression does NOT result in harm as envisioned by our colleagues. Suppressed levels of TSH that are associated with harm in Graves’ patients, should not be extrapolated to exogenous replacement with thyroid hormone. This section was difficult to put together and explain. This topic requires a thorough understanding of ADNPC as well as insight into the literature demonstrating that thyroid hormone is not harmful; Graves’ Disease is. By now, you should understand this but that does not mean that your colleagues will. Have empathy for them, you also would not have understood this, had you not had access to these courses and the literature presented.