Hypothyroidism Symptoms Often Remain Despite Treatment

Hypothyroidism – an underactive thyroid gland- is a common condition affecting approximately 10-12 million Americans. The vast majority of patients are treated with Thyroxine (brand name Synthroid) which is the thyroid hormone called T4. Though there are two thyroid hormones T3 (liothyronine) and T4, the vast majority of doctors have for many years replenished their patients’ T4 hormone as the standard treatment for their condition. Some physicians with a different approach to these patients have disagreed with the standard approach of utilizing only levothyroxine -T4- and advocate replenishment of both the T3 as well as the T4 hormone. After many years we may be seeing a greater acceptance of the idea that treatment with both T3 and T4 may prove to be a better approach for their patients. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987447/

Antonio C. Bianco, MD, PhD, is the immediate past president of the American Thyroid Association. He is a professor of Medicine at the Rush Medical School in Chicago, Illinois. He has just presented a scientific study showing that what is considered the successful medical treatment of hypothyroidism with levothyroxine-T4- leaves many patients still showing symptoms of their condition. He suggests that we may need to re-examine whether the standard approach should be continued, or whether the addition of T3 therapy should be practiced. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10801060/

Dr Bianco says, “These findings correlate with what patients have been telling us. This study documents for the first time, in an unbiased fashion, that patients on levothyroxine feel worse and are much less active than controls, exhibiting objective cardiometabolic abnormalities despite having normal TSH levels.” 

Despite normal TSH tests, these patients still have many nagging symptoms of hypothyroidism. “Patients complain of being depressed, slow and having a foggy mind,” he explains. “They have difficulty losing weight. They complain of feeling sluggish and have less energy. Yet we doctors keep telling them, ‘I’m giving you the right amount of medication and your TSH is normal. You should feel fine.'”

Research conducted by Bianco and his researchers at Rush Medical School in Chicago, Illinois was recently published in the Journal of Clinical Endocrinology and Metabolism. Their study found that patients taking T4-levothyroxine- who had normal TSH levels were more likely to be taking antidepressants than those with normal thyroid functioning. These patients were also less physically active, and weighed approximately 10 pounds more than people of the same height even though they had  consumed less calories per day.  Lastly they also found that these patients were more likely to be prescribed beta blockers which lower blood pressure, and they took more statin medications to reduce their cholesterol levels. Both depression and high cholesterol readings are known to be associated with hypothyroidism. But these patients are being told that they have been correctly, and thus successfully treated for their thyroid condition! 

The thyroid’s primary job is to regulate the basic body function called metabolism which is a part of and affects virtually every organ and function in the body. When thyroid hormones are low, as in hypothyroidism, the heart rate slows and the intestines process food at a reduced speed, causing constipation. The thyroid also affects the brain. ” Dr Bianco explains “Your brain turns off. Patients are tired, sleepy and might experience feelings of depression. If not treated, might slow down dramatically and slowly go into a sleep state, and eventually into coma.”  (in severe untreated cases).

Let us examine how T4 therapy has been practiced and evaluated for these many years, and the reasoning behind considering a new approach.  When patients have a blood test to evaluate their thyroid as a part of a routine “check up” the doctor will order the test called TSH -Thyroid Stimulating Hormone. When patients have an abnormally high TSH test it is a sign that the thyroid gland is not producing as much thyroid hormone as normal. The body, by having a high level of Thryoid stimulating hormone is telling us that our body wishes to have more thyroid gland and the thyroid should be   “stimulated” to produce more thyroid hormone if it could. But the thyroid isn’t functioning at its best it can’t make more thyroid hormone. So as treatment, the doctor prescribes the thyroid hormone T4 -thyroxine- to replenish the level of thyroid hormone in the system which is lacking because of their underactive thyroid gland. As a result of receiving the replenishment with T4 hormone the patients’ blood test TSH will go down, returning to the normal range. This will be the sign to the doctor that the thyroid hormone level in the body is normal and the patient has been successfully treated . 

The problem as shown above is that …

Hypothyroidism symptoms linger despite medication use and normal blood tests

This research gives voice to patients who have complained about symptoms which persist though they’ve been told their treatment has now returned their thyroid levels to normal. Patients who may have felt dismissed and forgotten now have evidence that their persistent symptoms are not just their imagination.

What About Also Giving People the T3 Hormone as a Better Treatment for Hypothyroidism ?

There are two types of thyroid hormones: T3 (triiodothyronine) and T4 (thyroxine). Back in the 1960s, patients with hypothyroidism were given pills containing both T3 and T4, which were made from desiccated thyroid glands, which were animal. But some of the scientific advancements in learning about the thyroid gland, may have actually promoted a misinterpretation by physicians leading them to prescribe only T4 which became the standard care given.

One physiologic discovery was that the thyroid mostly produces T4, which is turned into T3 naturally.  “The important thing to understand is that T4 is not the active hormone,” Dr.  Bianco says. “T4 must be converted to T3 by our bodies with an enzyme called deiodinase.” The medical community decided that , “hypothyroid patients should be given only T4 as opposed to giving desiccated thyroid with both T3 and T4. Then the body, in its wisdom, will make enough T3.”

This resulted in the widespread treatment of hypothyroidism with T4- levothyroxine. 

“That is how patients are generally treated and monitored today for hypothyroidism,” Dr Bianco explains. “While the therapeutic goal is to make patients feel better, symptoms alone are not utilized for judging adequacy of treatment. Blood TSH levels are. In other words, the dose of levothyroxine is adjusted based on the TSH levels and not whether or not the patient feels better.”

Now we arrive at the crux of the problem and the controversy and disagreement that has existed for many years regarding whether standard thyroid treatment is actually the best treatment or not. Is there a better alternative?

Because the majority of patients with hypothyroidism do well on levothyroxine monotherapy, which is considered a safe medication, the medical community has considered the treatment approach a success. However, there have always been a significant number of patients who have observed that they still have symptoms related to their hypothyroidism, despite being told that they have been treated successfully according to their blood test results. Patient advocacy groups have drawn attention to the plight of these patients who feel sick despite taking levothyroxine and having normal TSH levels.

As a prominent endocrinologist Dr. Bianco has many such patients who have been referred to him for care. He says, “What they’re looking for is someone to believe what they’re saying. When I say, ‘I understand and I believe you,’ many of my patients start crying. These patients have been suffering and physicians have been dismissing them.”

To learn more about why some patients were not feeling well in a completely objective, unbiased fashion, Rush researchers utilized a very large publicly available survey, called the U.S. National Health and Nutrition Examination Survey (NHANES). More than 10,000 people participated in this study. The survey combined interviews and physical examinations.

Sarah Peterson, phD, study author at the Rush University Medical Center said, “We looked to see how 52 clinical measures differed between the two groups. Individuals taking levothyroxine weighed significantly more and moved less, they were also more likely to take antidepressants than those who were in the control group.” There study was published with the title Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy?

 The Journal of Clinical Endocrinology 10.1210/jc.2016-2660

Throughout the many years that T4 monotherapy became the most frequently used treatment for hypothyroidism some medical practitioners whose practices have been termed Functional Medicine or Integrative Medicine continued using the thyroid medications which contain both the T3 and the T4 hormones together. After these many years the newly developed information highlighted here, may indeed give life to the point of view that we should return to what became viewed as the “old fashioned” way of treating hypothyroidism as perhaps better than what became the standard treatment for so long. https://drsobo.com/natural-thyroid/

A scientific review of the subject published by the NIH reviews the role of T3 in the treatment of hypothyroidism.


Hypothyroid patients who continue to have symptoms on levothyroxine monotherapy should talk to their physician about adding T3 to their thyroxine therapy or trying combination therapy- a pill that contains both T3 and T4. Further studies along these lines are supported by the American Thyroid Association. Meanwhile patients who are not doing well on T4-thyroxine-have the option of trying this decades old treatment to see if it works the best for them.

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Medically reviewed by Dr. Henry C. Sobo, M.D

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