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When Is Combination Therapy Better Than Synthroid?

Some people who don't feel completely well on levothyroxine alone do better on combination therapy. This includes both T4 and the active hormone T3.

Doctors prescribe the thyroid hormone treatment levothyroxine (Euthyrox, Levoxyl, Synthroid, Tirosint, Unithroid) more frequently than most other drugs in the pharmacy. In fact, more than 20 million Americans swallow one of these pills every day. Although levothyroxine alone is the standard treatment for people with underactive thyroid glands, not everyone taking this medication feels well. Could combination therapy work better for hypothyroidism than this single hormone?

Will Combination Therapy Work Better Than Synthroid?

Many readers tell us that they have trouble with levothyroxine alone. We recently heard from a reader who was struggling.

She wrote:

“I am desperate. I have had hypothyroidism for 21 years. For the last 10 years, I took 100 mcg of Synthroid.

“In February 2020, my yearly bloodwork showed my T3 level was a bit too high. My doctor dropped my Synthroid dose to 75 mcg. As soon as I went on that dosage, I gained 20 pounds in three months, I was depressed, my skin was dry, I lost a lot of hair and I felt like I was freezing all the time.

“When my levels were rechecked in July, my T3 was too low. My doctor put me on 100 mcg again. A few months later, after a recheck, she dropped the dose again, to 88 mcg, even though I still felt awful.

“I asked my doctor why I can’t lose the 20 pounds I gained. She told me she’s stumped and that I should exercise more, though I exercise every day and I don’t eat a lot.

Thyroid Specialist Had No Solution:

“A thyroid specialist told me that I should expect to gain weight because I am 50. Neither he nor my GP were in favor of me taking natural Armour thyroid, and neither one seems curious about my problem.

“I told both doctors that I’m cold when it is 96 degrees outside, I can’t lose weight, my skin is dry, I’m tired all the time, I have no energy and I’m sad a lot. Neither one is listening to me. All I want is for them to say, ‘Let’s get to the bottom of this.’ But they both said I should expect this because I’m 50.

“I hate feeling the way I do. Usually, when my medicine dose is too high, my heart beats fast, but I didn’t have that feeling when I was on the 100 mcg dosage. What else can I do?”

We responded that her symptoms are classic for hypothyroidism and suggested she see a different thyroid expert familiar with the most recent research. She took a copy of our eGuide to Thyroid Hormones with her to her next visit. It describes research showing that not everyone can convert T4 (levothyroxine) to T3 (liothyronine, the active hormone) efficiently. Some people feel better when they take combination therapy with both hormones.

In fact, a recent study compared levothyroxine alone, a combination of T4 and T3 and desiccated thyroid extract (Journal of Clinical Endocrinology and Metabolism, Oct. 21, 2021). TSH did not differ among groups, but people who were most uncomfortable on levothyroxine alone had a strong preference for combination therapy, because it helped them feel better.

Our reader responded:

“Thank you so much for your help. I ended up going to a third doctor, who was willing to listen to me. Even though I had 18 out of the 23 symptoms listed, she still thought it’s my age.

“She did run a blood test, though, and said if I still feel bad after two more months, she’d prescribe liothyronine. I also insisted on testing my antibodies. In her opinion, the test is a waste because it never shows anything, but she agreed.

“When my blood work came back, my thyroglobulin antibody was 34 and my thyroid peroxidase antibodies were 198, which is very high.

“It was a strange follow up visit. I had to ask her about my high antibodies. She said I have Hashimoto’s, which explains why my thyroid is not working.

“I’m pleased she gave me a prescription for 5 mcg of liothyronine, though. After just two weeks, I have much more energy and have lost 8 pounds. I’m no longer depressed, and I’m sleeping well without the suicidal thoughts that had bothered me for months. Your information helped me be prepared for the doctor visit and gave me the knowledge to ask for the right tests.”

Taking Armour as Combination Therapy:

Q. My thyroid gland was removed three years ago. I have never felt right on Synthroid. I’ve also tried a combination of Synthroid and Cytomel and recently Armour Thyroid.

Of all three, I’ve found Armour Thyroid is the best. I split it and take multiple doses throughout the day to avoid heart palpitations.

Most endocrinologists as well as primary care physicians adjust the thyroid dose based on the TSH test. That will be low when you take T3 (which is a natural part of Armour Thyroid). I’ve been informed that the blood test should be done in the early AM and food and thyroid meds shouldn’t be taken for 12 hours before blood is drawn for labs.

People Who Don’t Do Well on Levothyroxine Alone:

A. We consulted one of the world’s foremost authorities on thyroid function, Dr. Antonio Bianco, professor of medicine at the University of Chicago School of Medicine. He has found that up to 15 percent of patients don’t feel good on levothyroxine alone (Thyroid, June 2018). This may be due at least in part to genetic differences in the enzymes that convert T4 (levothyroxine) to the active T3 hormone (triiodothyronine) (Frontiers in Endocrinology, July 9, 2019).

Dr. Bianco points to evidence that a normal TSH (thyroid stimulating hormone) does not necessarily indicate optimal thyroid hormone activity throughout the body. Although most endocrinologists still use TSH as the gold standard and prescribe levothyroxine alone as treatment, Dr. Bianco suggests that treatment should be personalized. He and his colleagues look forward to prescribing a combination therapy that will be individualized and provide the hormones patients need. Armour and other desiccated thyroid extracts made from pig thyroid glands fall short. That’s because the ratio of T3 to T4 is different in pigs and humans.

As for the blood test, your advice is good. TSH levels are significantly lower after the morning meal (Indian Journal of Endocrinology and Metabolism, May-June 2017) than before it. Levels of free T4 do not appear to be affected by the time of day or whether the patient is fasting.

Who Will Benefit from Combination Therapy for Hypothyroidism?

The goal is for patients to feel good. For some patients, this will mean using combination therapy or desiccated thyroid extract such as Armour. Others do well on levothyroxine but may need to adjust when they take their medication. Synthroid, Levoxyl and probably generic levothyroxine may not be absorbed as well if taken at the same time as iron or calcium supplements. Even coffee can reduce absorption, so some people find that taking their thyroid hormone at bedtime works well.

Learn More:

People who would like to learn more about treating thyroid problems with combination therapy may wish to read our eGuide to Thyroid Hormones. You might also wish to listen to our interview with Dr. Bianco, which you can find here.

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About the Author
Terry Graedon, PhD, is a medical anthropologist and co-host of The People’s Pharmacy radio show, co-author of The People’s Pharmacy syndicated newspaper columns and numerous books, and co-founder of The People’s Pharmacy website. Terry taught in the Duke University School of Nursing and was an adjunct assistant professor in the Department of Anthropology. She is a Fellow of the Society of Applied Anthropology. Terry is one of the country's leading authorities on the science behind folk remedies..
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