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When Low Thyroid Symptoms Don’t Go Away…Even on Synthroid


Is your doctor giving you Synthroid to treat low thyroid hormone levels (hypothyroidism)—but you still have disturbing symptoms? You’re tired…struggling with weight gain…perhaps especially sensitive to cold. Yet your doctor doesn’t have a solution.

You’re not alone. As many as 15% of patients taking meds to correct hypothyroidism continue to suffer the same symptoms that brought them to their physicians in the first place.

And nearly half of them have normal thyroid hormone levels on blood tests.

What’s a suffering patient to do? There is another approach—one your doctor may not tell you about. It’s one that combines the storage (or “pro-hormone” form), T4, and the active form of thyroid hormone, T3. To learn more, we spoke with Jacqueline Jonklaas, MD, PhD, associate professor of endocrinology and medicine at Georgetown University Medical Center in Washington, DC, who recently reviewed the scientific literature about this approach.


As many as 27 million Americans have low thyroid levels. It’s more common in women than in men. In many cases, the cause is an autoimmune disease (Hashimoto’s), in which the body produces antibodies to the thyroid gland. Medical procedures, including treatment of thyroid cancer, can also bring on a low thyroid condition.

The majority of people with hypothyroid disease are successfully treated with a drug called levothyroxine (Synthroid). It’s a synthetic form of T4, the pro-hormone that the body converts to T3, the active thyroid hormone the body can use. “The vast majority of patients feel pretty good on levothyroxine, but there is a percentage of patients—between 5% and 15%—who don’t,” says Dr. Jonklaas.

Why doesn’t T4 work for them? One explanation is that some people’s bodies are not efficient at converting T4 to T3. Indeed, about 15% of the population, notes Dr. Jonklaas, has a genetic abnormality that, to one degree or another, may interfere with the conversion of T4 to T3.

One obvious solution is to simply give patients T3. There are therapies that contain T3 either on its own or in combination with T4. Medical groups, including the American Thyroid Association, are very wary of these alternatives to levothyroxine because of their potential side effects (which we’ll discuss below). Some physicians and patient advocates believe that T3 therapies can be used safely in patients who do not respond well to levothyroxine alone. Mary Shomon, a patient advocate and author of The Thyroid Diet Revolution: Manage Your Metabolism for Lasting Weight Loss, has hypothyroid disease herself. “The medical world pushes Synthroid to the exclusion of any other options,” she says. “My battle cry is not that any one drug is better than the other, but that patients need to know about all of the options.”


One of the concerns with taking T3 is that the available pills are short-acting medications. This results in high levels of T3 right after the drug is taken and low levels when it wears off. High levels of T3 can be harmful—they’re associated with insomnia and anxiety and can lead to dangerous rapid heart beat. Prolonged high T3 levels can even harm the heart and the bones. One way to avoid these peaks and troughs in T3 levels is to cut pills into smaller sizes and take these smaller amounts of  the medication at more frequent intervals during the day. Another solution is to have a compounding pharmacy make lower-dose capsules—though there is a concern about the potency of such capsules, since these pharmacies are only partly regulated by the Food and Drug Administration along with a patchwork of state regulations, some more stringent and some less so.

In the past, most patients did in fact take a drug that was a combination of T4 and T3 hormones. The drug, Armour Thyroid, is a dried form of pig thyroid. But pig thyroid has a high proportion of T3 to T4 and was found to increase risks for heart and bone disease. Although doctors almost universally now prescribe synthetic T4 (Synthroid) instead, Armour Thyroid is still available and some “nonresponders” to T4 swear by it.

Although recent studies have not shown that a T3/T4 combination is more effective than T4 alone, Dr. Jonklaas says that many of those studies had shortcomings. For instance, in some of the studies, T3 was given only once a day, and most of the studies were short-term and so unable to assess long-term effects—good or bad. “We don’t really know whether taking T3 for five years will hurt bone density or increase the risk of having cardiac problems,” she says. “We do have anecdotal and common experience of patients about how they feel better.”


Until more research is conducted, Dr. Jonklaas advises trying to tweak T4 therapy as much as possible before trying combination T3/T4 therapy. If you do try combination therapy, your doctor will need to closely monitor your TSH (thyroid-stimulating hormone, a measure of your pituitary assessment of your thyroid status), thyroid hormones, heart rate, bone density—and any other side effects (such as rapid heart beat, insomnia or anxiety) you might experience.

Bottom line: If you don’t feel well even with Synthroid and your endocrinologist is not willing to consider other options, it may be time to find a new physician—someone who is less focused on lab results, more focused on symptom resolution…and open to discussing alternative treatments.

To learn more about low thyroid, see Bottom Line’sHypothyroidism: The Thyroid Problem That’s Tricky To Spot.” If you have only moderately sluggish thyroid, you may also be able to stimulate it through diet alone.

Source: Jacqueline Jonklaas, MD, PhD, associate professor of endocrinology and medicine, Georgetown University Medical Center, Washington, DC, and author of study titled “Risks and safety of combination therapy for hypothyroidism,” published in Expert Review of Clinical Pharmacology. Date: September 27, 2016 Publication: Bottom Line Health
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