If T4 Does not Improve Symptoms, and Normalizing TSH Does not Guarantee or Infer Improvement in Symptoms, Then How Should we Treat Patients?
If T4 Does not Improve Symptoms, and Normalizing TSH Does not Guarantee or Infer Improvement in Symptoms, Then How Should we Treat Patients?
Written by Neal Rouzier, MD
Recommended Pre-Reading: Treating T3 Deficiency: The Evidence You Need
Treatment Scenario
Your 41 y/o PCOS patient that is optimized on thyroid returns with concerns that her PMD does not like/approve of DTE.
She notes that she is finally feeling well and experiencing success with weight loss.
The PMD also is upset with the suppressed TSH level but does not understand the low Free T4 levels. The PMD states that the patient is thyroid toxic despite no symptoms or side effects of excess thyroid, the pulse rate is 60, and the patient feels normal. (How is that thyroid toxic?)
Unfortunately, these patients take a lot of time and effort, but their concerns are legitimate as their doctors scare them. It is also unfortunate that most doctors do not understand thyroid (but I didn’t either). Patience and understanding are required. Review the literature presented in Treating T3 Deficiency: The Evidence You Need (Part 2) with the patient, but DO NOT give to her doctor. Explain why her doctor believes and says what he says. However, it wasn’t until the patient started taking thyroid that her symptoms, QOL, and well-being improved. The patient has to decide which horse to ride as she can’t ride 2 horses at the same time and may have to change doctors, unfortunately, in order to continue her thyroid treatment. The patient’s PMD cannot be convinced or educated. Let the patient decide if she wishes to feel well or go back to her old self and take the T4 and stop the DTE. Use the improvement in Free T3 levels to help educate the patient.
Haven’t taken training with us yet, but interested in learning more about the value and efficacy of BHRT as an alternative to medication-based therapies? Please consider our four part Hormone Optimization Workshop Series, and start training with us at Part I: Discover the Power of BHRT.
If you are interested in learning more about treating T3 deficiency, please consider taking our thyroid series.
Table of Contents
How Should We Treat Patients?
In the first webinar, Treating T3 Deficiency: The Evidence You Need (Part 1) we reviewed the inability of TSH to reliably predict symptomology as well as its lack of benefit in monitoring therapy, contrary to what we have been taught for 50 years. The active hormone at the cell level, Free T3, was much more predictive and demonstrative of symptom improvement. We also reviewed the continued preferential use of T4 preparations over desiccated thyroid by thyroid organizations. The BMJ authors recommended, however, that clinical parameters and symptomology should play the major role in regulating thyroid replacement and not the TSH. Lastly, the final paper introduced the studies demonstrating patient dissatisfaction with standard T4 treatment with preference to the use of T3 in place of T4. Normalizing TSH with T4 did not improve T3 levels or symptoms as expected, thereby calling for the preferential use of monitoring symptoms and clinical parameters instead of the gold standard TSH. So, if T4 does not improve symptoms, and normalizing TSH does not guarantee or infer improvement in symptoms, then just how should we treat patients?
DTE VS T4-Alone
Only those patients with suppressed TSH levels and high serum T4 showed improvement. As the result, patients are demanding treatment with DTE in preference to T4-alone therapy. Patients on DTE had less problems with weight, fatigue, mood, and energy, and memory. A landmark study published in Thyroid confirmed these findings. The prevailing viewpoint that TSH normalization with T4 resolves all symptoms of thyroid dysfunction was disproven. This was another study that utilized T4-alone monotherapy that resulted in suppression of Free T3 levels, the opposite of what we expect. In addition, patients’ symptoms did not improve until the TSH was completely suppressed. 84% of patients that had residual symptoms while on T4 had resolution of symptoms when switched to combination DTE. As I see clinically, DTE increases Free T3 to above normal and suppresses T4 to below normal due to TSH suppression and the resultant decrease in T4 production by the thyroid gland. Patients on T4-alone expressed dissatisfaction with their therapy as well as with their physicians. Imagine that.
There are more and more data proving that treatment with T4-alone results in patient dissatisfaction despite achieving normal TSH levels. Several landmark papers demonstrated a superior effect of DTE (desiccated thyroid extract). In order to counter these studies, a dozen pharmaceutical industry-sponsored studies failed to show any superiority over T4-alone therapy, as would have been predicted. However, the studies were flawed (intentionally) by using subtherapeutic doses of T3 which were destined to fail. Patient preference for DTE increased as did the pushback against its use by the endocrine world. However, and unexpectedly, T4 was shown to raise T4 levels but suppress T3 levels, particularly in patients that were S/P thyroidectomy. Serum T3 levels were markedly lower post-surgery than pre-surgery indicating ineffective conversion of T4 to T3 despite normalization of TSH levels. This was also evidenced by increased cholesterol levels in response to the low serum T3 levels and tissue T3 levels. Once again, administration of T4-alone resulted in worsening in clinical parameters, serum T3 levels, and tissue markers of metabolism.
Improving Symptoms
Subtle symptoms will improve on thyroid replacement with T3:
“The patient may not have realized how poorly he felt until he felt better.”
“A therapeutic trial of thyroid may be attempted in patients with non-specific symptoms and elevated cholesterol.”
You mean, they were not hypothyroid but just had symptoms of low thyroid, and were treated with thyroid? Yes.
“A combination of T4 & T3 makes logical and physiologic sense.”
Just because the TSH is normal does not guarantee that the patient is normal, or feels normal, as evidenced by the studies that address the issue of persistent symptoms despite “normal” TSH.
T4 Monotherapy
The hypothesis that T4 monotherapy will provide for adequate and physiologic regulation of serum T3 levels has been held with much conviction. It is false.
In fact, most studies demonstrate that replacement of T4 actually suppresses production of and conversion into T3, the opposite of what we would logically think would happen. Instead of raising T3 levels as expected, T3 levels fall below what they were at baseline. This accounts for the weight control issues seen with T4-alone as well as an increase in BMI and cholesterol in some patients. This is also why some thyroid associations claim that Free T3 is a lousy test. It is not a lousy test, rather, it is an excellent test, but the endocrine world does not understand why lower T3 occurs when giving T4. And many studies demonstrate this but the endocrine world fails to appreciate this. This also explains the residual effects and symptoms and metabolic problems with T4-alone in some patients.
So, if the hypothyroid patient’s symptoms do not improve on T4 therapy with a normalized TSH, then how should we treat a non-hypothyroid patient with identical symptoms and a normal TSH? The guidelines state that we should not treat these patients if the TSH is normal, but the patient still has low thyroid related symptoms. However, studies indicate that thyroid hormone is commonly prescribed for euthyroid patients with fatigue, obesity, depression and with good results.
Should we treat the lab test (as per AACE) or the patient (as per the literature demonstrating improvement with T3 administration?
“T4 treated patients experience higher BMI and weight, fatigue, and commonly take HTN, DM, and cholesterol meds.”
Why is that?
Also, T4 therapy does not render patients clinically euthyroid, but they are biochemically (normal TSH) euthyroid. “Endo guidelines should be revisited.” I review all the foregoing literature in this webinar with a point-counterpoint discussion.
Haven’t taken training with us yet, but interested in learning more about the value and efficacy of BHRT as an alternative to medication-based therapies? Please consider our four part Hormone Optimization Workshop Series, and start training with us at Part I: Discover the Power of BHRT.
