Thyroid Hormone Replacement Therapy: A Beginner’s Guide to Levothyroxine and Synthroid

two prescription bottles with pills next to them
Dr. Sharon Orrange
Dr. Orrange is an Associate Professor of Clinical Medicine in the Division of Geriatric, Hospitalist and General Internal Medicine at the Keck School of Medicine of USC.
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Synthroid (levothyroxine) is the most commonly prescribed medication in the US, and is used to treat hypothyroidism—often for a lifetime. Symptoms of hypothyroidism, or under-active thyroid, may include fatigue, weight loss, anxiety and depression. Here are seven questions I get asked a lot about levothyroxine and thyroid hormone replacement therapy.

What is levothyroxine?

Synthetic thyroxine (T4) comes as brand-name Synthroid or generic levothyroxine. T4 is what is known as a “prohormone”; it’s made by the thyroid gland and gets converted to the active hormone, T3, in other body tissues. The advantage to taking T4 over T3 is that your own body’s mechanisms can control how quickly T4 is converted to T3.

What’s the difference between levothyroxine and Synthroid?

Generic levothyroxine may differ slightly from Synthroid in terms of how well it’s absorbed. That’s why it’s preferable to stick with either one if possible. Both the American Thyroid Association and the Endocrine Society recommend that patients remain on Synthroid if that’s what was initially prescribed. If you are on generic levothyroxine, try to stick with the same generic manufacturer—your pharmacist can help you with that.

What about switching from Synthroid to a desiccated thyroid extract like Armour Thyroid? Many studies have compared Synthroid to desiccated thyroid extract and revealed no differences in symptoms and neurocognitive measurements between the two groups.

What’s the best way to take levothyroxine?

The average replacement dose of T4 in adults is approximately 1.6 mcg/kg per day, which would be 112 mcg per day in a 70-kg adult, but this is not a one-size-fits-all recommendation.

Synthroid should be taken on an empty stomach, ideally an hour before breakfast. Another option is to take it at bedtime if you’ve had nothing to eat for several hours. High-fiber diets, coffee, and iron and calcium supplements can interfere with levothyroxine absorption by up to 30%.

Be careful if you take other medications. People on estrogen therapy may need to up their levothyroxine dosage. And proton pump inhibitors like omeprazole and Nexium can limit levothyroxine absorption.

When should I get a TSH blood test?

A TSH (thyroid stimulating hormone) blood test tells doctors whether or not your thyroid hormones are back to normal. Patients who are treated with T4 usually begin to see symptoms improve within two weeks, but complete recovery can take at least six weeks. At six week, a TSH blood test should be performed. Once TSH levels in patients with primary hypothyroidism return to reference range, periodic monitoring is warranted.

What are normal TSH blood test results?

There’s plenty of controversy here. Most labs consider normal TSH levels to be under 4.5 to 5.0 mU/L, but some argue that the upper limit of normal range should be reduced to 2.5 mU/L. That’s because most “normal thyroid” volunteers have TSH blood values between 0.4 and 2.5 mU/L.

The aim should be to keep TSH within normal reference range (about 0.5 to 5.0 mU/L), but if you continue to have hypothyroid symptoms, talk to your doc about whether you should increase your dose of levothyroxine and aim for a TSH value in the lower half of the normal range (0.4 to 2.5 mU/L).

What happens if I take too much levothyroxine?

One potential effect of too much levothyroxine that might seem nice is weight loss, but over-replacement with thyroid therapy so your TSH levels become too low is a bad idea—and I see it all the time.

The main risk is atrial fibrillation, a dangerous heart rate abnormality, which occurs three times more often in patients who are on too much levothyroxine. You may also have accelerated bone loss and therefore, a higher risk of fractures.

Should I take levothyroxine (T4) alone or with liothyronine (T3)?

Some folks on levothyroxine with normal TSH levels still experience hypothyroidism symptoms. In fact, 9% to 13% of people taking Synthroid with normal TSH values still report impaired psychological well-being.

Combination therapy is an area of controversy. Here’s what the science says: Years of studies comparing T4 alone to T4 plus T3 (Cytomel) show that the latter is not superior to T4 alone in managing symptoms of hypothyroidism.

Hope that helps.

Dr O.

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