Recent Literature Supports That Low Free T3 was the Highest Independent Predictor of Death in CV Patients
Recent Literature Supports That Low Free T3 was the Highest Independent Predictor of Death in CV Patients
Written by Neal Rouzier, MD
Recommended Pre-Reading: More Proof and Reasoning that T4 Monotherapy Results in Inadequate Conversion
A 59 y/o female with CVD is referred by her friend for evaluation of hypothyroidism. Laboratory tests consistently show a mildly elevated TSH and normal Free T4. Despite multiple attempts to try to get her PMD to prescribe a trial of thyroid hormone, the PMD insists that thyroid hormone is not indicated in her case. He cites recent evidence that patients experience no benefit from thyroid hormone replacement and that there is a potential for harm. In addition, thyroid hormone administration can be burdensome by having to take daily medication, increased costs of medication, follow-up visits, and blood tests, which all can drive up costs without any benefit.
This patient is upset that no one takes her complaints seriously and she is frustrated in feeling consistently worse with time. She states that she is depressed because she feels lousy, and no one cares. She is increasingly upset with her doctors, the weight gain, fatigue, and lack of energy that affects her work and QOL.
The TSH is marginally elevated at 6.0 and the Free T4 is normal. However, the Free T3 level is low at 2.0. This patient was slowly titrated on DTE with tremendous improvement in her symptoms of low thyroid. This is a perfect example of what our esteemed WLM endocrinologist, Dr. Kadambi, terms thyroid hypofunction.
You review with her all the medical literature demonstrating an increase in CVD and mortality with low Free T3 levels.
She wonders why her doctors don’t know this and never tested her. In addition to feeling better and losing weight (finally), there is significant improvement in all her lipid parameters and Apo-B levels. The HgBA1C which became elevated while on high dose statin therapy for 5 years has now normalized. Putting this patient on your HRT program further improved her dyslipidemia and insulin resistance.
She is so gracious for your care and states that you gave her life back to her that no one else did. And this is what makes medicine fun.
If you are interested in learning more about treating T3 deficiency, please consider taking our thyroid series.
Treating T3 Deficiency Recap
In the first webinar, Treating T3 Deficiency: The Evidence You Need (Part I), we reviewed recent literature demonstrating that TSH was a poor indicator of metabolic severity. In addition, studies also indicated that normalizing TSH values did not indicate improvement in symptoms or clinical parameters, rather Free T4 and Free T3 levels better demonstrated symptomology even though TSH levels were normal. Clinical improvement did not correlate with normalization of TSH level indicating that the TSH level is not an adequate test for monitoring therapeutic improvement. However, Free T4 and Free T# levels did correlate with improvement in symptoms. Nevertheless, TSH is still regarded as the gold standard in adjusting thyroid hormone even though experts call for eliminating TSH normalization as the method of choice for adjusting therapy.
In the second webinar, Treating T3 Deficiency: The Evidence You Need (Part 2), we reviewed literature demonstrating that thyroxine (T4) therapy did not improve symptoms or clinical parameters despite it being the treatment of choice by thyroid organizations. We discussed why this occurs in that T4 frequently does not convert well into T3 despite the strongly held conviction that it always does. Studies demonstrate that it can even suppress or lower T3 levels, contrary to what we intuitively think will occur. This is important to keep in mind for this webinar as we will further review studies that prove T4 therapy does not improve symptoms or metabolic parameters despite normalization of TSH levels. However, in the last webinar we reviewed studies that demonstrated use of T3, or desiccated thyroid, did improve symptoms. The Free T3 levels did improve with T3 therapy, whereas the levels were suppressed on T4 therapy. No wonder symptoms did not improve on T4, yet it is fascinating endocrinologists do not grasp the reasons why patients do not improve on T4 alone.
In this webinar, Treating T3 Deficiency: The Evidence You Need (Part 4), we will further review the problems with using T4-alone as researchers recommend discontinuing thyroid hormone if symptoms do not improve, even in patients with subclinical hypothyroidism and elevated TSH levels. Based on multiple studies demonstrating no improvement in symptomology in subclinical hypothyroid patients, I find it appalling researchers conclude that thyroid hormone should not be used in subclinical hypothyroid patients and that a TSH level of less than 20 should not be treated, purely based on their observations that T4-alone does not work in patients with SCH. Obviously, they remain oblivious to all the studies demonstrating that addition of T3, or desiccated thyroid, would improve symptoms and allow these patients to be treated and their QOL improved. There is no subject in medicine that is as controversial and contentious as thyroid administration.
Treating T3 Deficiency (Part 4)
“There were 21 trials reviewed. Expert researchers state that thyroid hormone consistently demonstrates no clinically relevant benefits for quality of life or symptoms, including depression, fatigue, and BMI. Thyroid hormone had no effect on CVD events or mortality. The panel concluded that all adults with subclinical hypothyroidism would not benefit from thyroid hormone replacement. Other concerns were the burden of taking life-long thyroid hormone and potential harms.” We are obviously not on the same page as these folks. However, I do have to agree with them that T4 does not work and all the studies I presented in the first 3 webinars demonstrate this. However, I completely disagree with their conclusion to not use any thyroid hormone at all. What about all those RCTs demonstrating that DTE worked when T4 did not? So, I agree with the panel to not use T4 but to completely ignore all the studies demonstrating that DTE is efficacious and could be utilized in this setting is disturbing and disappointing, but not unexpected. More so, this panel of experts completely ignore the adverse CVD effects of SCH and the reported benefits of thyroid replacement in reducing CVD.
I have included a rebuttal to the above expert opinions. A well versed and experienced psychiatrist has offered his opinion and insight to using thyroid hormone. He calls for not allowing endocrinologists to treat thyroid hypofunction, rather real doctors like himself should be treating patients. He has tremendous experience in using T3 and DTE as do most psychiatrists. Odd that a psychiatrist would recommend that he treat hypothyroid patients (and euthyroid patients) and not an endocrinologist. Imagine the gall of that psychiatrist to suggest that endocrinologists not treat hypothyroid patients because they don’t know how! Obviously, he has insight and experience that most endocrinologists and our peers do not as he too sees patients that improve on his thyroid regimen that did not improve under care of other doctors.
The internet is full of posts from patients that truly feel and function better on DTE despite the extreme pushback from the endocrine world. I find it ludicrous to ignore patients and studies that demonstrate improvement on DTE. The politics and economics and cognitive dissonance dictate the endocrine society guidelines. I still see no harm in letting the patient attempt a trial of DTE when there is no harm to DTE in any study. And that is what Dr. Pepper recommended in his paper, a trial of thyroid hormone to evaluate if patients do improve on DTE. And as he explains, it is not due to a placebo effect as there are long-term improvements that would not be seen with any placebo effect. A recent study from Endocrine Reviews further demonstrates this controversy. Dissatisfaction with T4 monotherapy remains high. Persistent symptoms associated with T4 monotherapy are due to low Free T3 levels. (Why is this ignored by thyroid organizations? One would think that the experts would grasp this, but they don’t). “Tissues are closest to euthyroidism at a TSH of 0.03.” Wow. And the hypothalamus is insensitive to T3 but sensitive to T4 thereby not sensing tissue hypothyroidism with low Free T3 levels, thereby resulting in symptoms of low thyroid but normal TSH levels. “A normal TSH does not indicate a euthyroid state.” (So eloquently stated). This paper puts the entire thyroid issue in perspective, explaining the physiology of lack of improvement with T4-alone therapy as well as the therapy which has been proven efficacious-the addition of T3. However, due to the prior 12 studies lacking any benefit of adding T3 (low dose) to T4, the endocrine world will reject and ignore this paper. (Confirmation bias at its finest).
A study published in Clinical Endocrinology demonstrated a decrease in lipids and a decrease in CIMT after thyroid treatment. And the reason the panelists in the first study don’t want to lower cholesterol and reduce CIMT is? A similar study in Endocrine Journal demonstrated the same reduction in CIMT with thyroid hormone which resulted from a decrease in lipids. A third study demonstrated the same-a decrease in lipids and CIMT. See the trend here? Amazing that these studies are ignored. Finally, a meta-analysis published in the BMJ demonstrated thyroid replacement improves all lipid parameters, blood pressure, lipoprotein-a, and CIMT. (Statins DO NOT do all that but everyone is on statins but not thyroid hormone). A separate meta-analysis in a cardiovascular journal (Journal of Atherosclerosis) demonstrated improvement in all lipid parameters as well as a decrease in CIMT. Imagine a cardiologist prescribing thyroid hormone to treat CVD and dyslipidemia. The last article appeared in the Journal of Atherosclerosis demonstrated that patients in the upper end of thyroid function had less CIMT compared to low normal thyroid function that had increased CIMT. So, where would you like your levels to be? What take away should be gleamed from this paper? Yet, experts recommend that low thyroid hormone (high TSH) not be treated. So, they want to increase CVD by keeping thyroid function low? Hmmm.
As far as other CVD studies, a paper published in Circulation proved an increase CVD with low Free T3 levels. In fact, a low Free T3 level was the most important predictor of cumulative death, followed by dyslipidemia and low CO. Low Free T3 was the highest independent predictor of death in CV patients. And so, how could we further lower Free T3 in CV patients and increase their risk for CVD and mortality? Give them T4 which suppresses T3! Great. And how do we then raise Free T3 levels? “Yea, but the guidelines state not to use T3 or DTE!” Hmmm. Low Free T3 levels also predicted increased CHF and death from CHF. Do you know any cardiologists that prescribe T3 or DTE to patients with CVD or CHF? T3 administration in every study improved CO and decreased CHF symptoms but is entirely ignored by the cardiovascular and endocrine worlds. Sigh. Now we see why the psychiatrist was so adamant in claiming endocrinologists should not treat patients with thyroid hypofunction because the are against using T3 or DTE as per their guidelines.