In the early 1900s, a synthetic thyroid hormone called levothyroxine was developed. Today, it is the standard treatment for hypothyroidism and is one of the most prescribed drugs in the U.S. What makes levothyroxine so popular? What side effects does it cause? Read on to find out.
What is Levothyroxine?
Levothyroxine is a prescription medication primarily used to treat hypothyroidism, a condition where the body doesn’t create enough thyroid hormones. Some brand names of levothyroxine include Synthroid, Levoxyl, Unithroid, and Levothroid [1].
Levothyroxine is one of the most commonly prescribed medications in the United States [1].
Levothyroxine acts as a synthetic version of T4 (thyroxine), one of the main hormones that the thyroid gland releases [1].
It is also sometimes used off-label to treat other thyroid disorders, such as goiter and thyroid cancer [1].
Overview of Thyroid Hormones
The thyroid gland produces and secretes two important hormones, thyroxine (T4) and triiodothyronine (T3) [2].
T3 is the active form of the two – it’s the hormone that primarily affects our body. The biological effects of T3 include changes to heart rate, breathing, and metabolism, to name a few [2].
Although T3 does most of the work, there is actually much more T4 in the blood. In fact, the thyroid gland releases about 14 times more T4 than T3 [3].
T4 is useful because it has a longer half-life than T3. This allows the body to convert T4 into T3 when needed. In other words, T4 acts as a stable source of T3 in the body [4].
It’s important for the body to regulate the levels of thyroid hormones in the blood. Having too much or too little can cause health problems [4].
How Does Levothyroxine Work?
Levothyroxine is a man-made version of T4. When the drug is absorbed into the blood, it is converted into T3 just like normal T4 [4].
Simply put, levothyroxine is a T4 substitute for those that cannot make enough of their own [4].
What Is Hypothyroidism?
People with hypothyroidism produce low amounts of thyroid hormones. This is usually due to problems with the thyroid gland [5].
A common cause of hypothyroidism is Hashimoto’s disease, an autoimmune disorder that destroys the thyroid gland [5].
Some other causes include a lack of iodine in the diet and pregnancy [5].
The effects of hypothyroidism can vary and some people may experience no symptoms at all [5].
Some common symptoms include [5]:
- Tiredness
- Weight gain
- Sensitivity to cold
- Constipation
- Dry hair and skin
- Voice changes
Uses of Levothyroxine
FDA-Approved Uses
1) Hypothyroidism
Levothyroxine is primarily used to treat thyroid hormone deficiency, also known as hypothyroidism. It is usually the first choice for thyroid hormone replacement therapy [1, 6].
Both the American Thyroid Association and the American Association of Clinical Endocrinologists recommend levothyroxine as the preferred medication for hypothyroidism [1].
This recommendation is based on strong clinical evidence of its effectiveness and safety. Other factors like good absorption, a long half-life, and low cost also support its use [1].
In the past, a drug called desiccated thyroid (brand name Armour Thyroid) was the primary choice for hypothyroidism. This drug is an animal extract that contains both T4 and T3 (the active form of T4) [6].
However, there are several reasons why levothyroxine came to be the standard.
One reason was the discovery that most T3 in the body comes from T4 conversion. Researchers also found that the thyroid gland mostly secretes T4 [6].
These findings imply that replacement with T4 alone may be better than products that contain both T3 and T4. Other factors include safety concerns over the inconsistency of desiccated thyroid products [1, 6].
2) Myxedema Coma
Myxedema coma is a severe form of hypothyroidism that often requires immediate thyroid replacement and hospitalization. The injectable form of levothyroxine is approved for treating this condition [1].
Research suggests that high doses of levothyroxine may reduce the risk of death associated with myxedema coma. It may also help restore heart and lung function [7, 8, 1].
3) Thyroid Cancer and Goiter
Levothyroxine is sometimes used to help with specific types of thyroid cancer and goiter. In these conditions, the thyroid gland can swell up or develop small nodules [9, 10].
If this happens, a strategy called TSH suppression therapy is sometimes used. Levothyroxine suppresses TSH levels in the blood, which may help control the size of the thyroid gland [9, 10].
Multiple clinical trials suggest that TSH suppression with levothyroxine is effective at reducing thyroid size [11, 12, 13].
However, there are some risks as well. TSH suppression with levothyroxine may increase the risk of heart disease as well as osteoporosis. A doctor will weigh the benefits and risks when considering treatment with levothyroxine in these types of cancer [14, 15, 11].
Off-Label Uses
Levothyroxine is used for several off-label conditions, which we’ll discuss in the following sections. If you are prescribed levothyroxine, always take the medication as directed by your doctor.
4) Subclinical Hypothyroidism
Subclinical hypothyroidism is a mild form of hypothyroidism where thyroid hormone levels are normal, but TSH levels are mildly elevated [16].
This condition can develop into actual hypothyroidism. It also may be a risk factor for developing heart issues [16].
There is some debate on whether subclinical hypothyroidism should be treated.
According to guidelines put out by the American Association of Clinical Endocrinologists and the European Thyroid Association, levothyroxine is recommended in patients with subclinical hypothyroidism who have persistently elevated TSH and free T4 within normal range [17, 18].
However, a systematic review of 12 studies including 350 people found no benefit with levothyroxine. It did not reduce the risk of death or prevent heart problems associated with subclinical hypothyroidism [19].
Levothyroxine Is Not for Weight Loss
The FDA has placed a statement on all levothyroxine products explicitly warning against using it for weight loss purposes.
One of the well-known symptoms of hypothyroidism is weight gain. Restoring thyroid hormones to normal levels can reverse this weight gain. This has led some people to believe that levothyroxine can be used to lose weight.
One issue is that high levels of thyroid hormone can cause life-threatening toxicity. This is especially true for people with normal thyroid hormone levels who take levothyroxine [20].
Beyond that, levothyroxine may not even cause significant weight loss.
In a study of 101 patients with hypothyroidism, levothyroxine reduced body weight in only 52% of people. For those that did see a benefit, the effects were mild – the average weight loss was about 8 lbs [21].
Bottom line: Using levothyroxine for weight loss is dangerous and ineffective.
Levothyroxine Safety
Side Effects
Levothyroxine can cause several side effects. If any side effects persist or worsen, let your doctor know. This is not a complete list of possible side effects. Tell your doctor if you experience any serious side effects or notice any effects not listed here.
Some common side effects include [22]:
Some serious side effects include [22]:
- Mood or mental changes
- Shortness of breath
- Chest pain
- Irregular heartbeat
- Swelling in the hands, ankles, or feet
Often, side effects are due to imbalances in thyroid hormones and not from the medication itself. If thyroid hormone levels are within normal range, side effects are usually uncommon [1].
Warnings
Risk of Bone Loss
Based on initial reports, the FDA warns that levothyroxine may cause bone loss, especially in postmenopausal women [22].
Recent research has revealed conflicting results. For example, a large review of 63 studies concluded that the scientific evidence was unclear, even in postmenopausal women. Multiple recent clinical trials have also found no effects on bone health [23, 24, 25, 26].
In any case, the lowest effective dose of levothyroxine should generally be used to achieve the desired clinical response, which a doctor will determine [22].
Risk of Heart Disease
Those with cardiovascular diseases should be careful when using levothyroxine [27].
Thyroid hormones play a major role in heart function. Overtreatment with levothyroxine can lead to an irregular heartbeat and potential heart attack [27].
In general, those at risk for heart disease should start levothyroxine on a lower dose and be closely monitored [22].
Pregnancy and Breastfeeding
Levothyroxine is considered safe during pregnancy [28].
Clinical trials have not revealed any safety risks to the fetus. For this reason, the FDA considers it a low risk during pregnancy [29].
Pregnancy can cause hypothyroidism in some women, as thyroid hormone requirements increase during pregnancy. This means that if you’re pregnant, your doctor may need to increase your regular dose of levothyroxine [28, 30].
Uncontrolled hypothyroidism during pregnancy can increase the risk of pregnancy complications [28].
Treatment with levothyroxine may decrease the risk of pregnancy loss, premature delivery, and low birth weight [31].
Levothyroxine is also considered safe during breastfeeding. Small amounts of thyroid hormones are found in breast milk, but no safety concerns have been found with levothyroxine. In fact, thyroid hormones play an important role in maintaining lactation [32].
However, you should talk to your doctor before using levothyroxine while breastfeeding.
Let your doctor know if you are taking levothyroxine and are pregnant or plan to become pregnant. Your doctor may need to monitor your hormone levels or adjust the dosage.
Contraindications
There are several cases where levothyroxine should not be taken.
Levothyroxine should be avoided in conditions that raise thyroid hormones (such as thyrotoxicosis). This combination can lead to dangerously high levels of thyroid hormone [33].
This drug can have negative effects on the heart. Individuals who have recently experienced a heart attack should not take levothyroxine [34].
People with uncorrected adrenal insufficiency should also avoid levothyroxine. In this disorder, thyroid hormones can trigger an adrenal crisis, a life-threatening condition [35].
Those who are allergic to any of the components inside levothyroxine should not take it.
Drug Interactions
The following drugs have been reported to interact with levothyroxine. However, this is not a complete list, let your doctor know of all the medications you are currently taking to avoid any unexpected interactions.
- Calcium carbonate (Tums)
- Antacids that contain aluminum and magnesium
- Sucralfate
- Iron supplements
- Heartburn drugs (Prilosec, Nexium, Prevacid)
- Dietary fiber
A recent small study suggests there may be an interaction with milk as well [36].
Many of these interactions reduce the absorption and effectiveness of levothyroxine. If a drug interaction cannot be avoided, usually the dose and timing of levothyroxine are changed [37].
Levothyroxine Dosage & How to Take
Dosage
Levothyroxine is usually taken as a tablet – strengths range from 25 to 300 micrograms.
Other forms like capsules, liquid solutions, and injections also exist. They are typically reserved for special situations (such as solutions for those who can’t swallow large tablets).
Dosing in hypothyroidism is individualized and based on TSH and T4 lab tests [1].
Lab values are usually monitored every 6 – 8 weeks and the dose is adjusted as needed. Once TSH and T4 become stable on a dose, monitoring is usually extended to every 6 – 12 months [1].
Levothyroxine can take a while to work, peak effects might not be seen for 4 – 6 weeks [1].
The average dose of levothyroxine is about 100 to 125 micrograms per day for an adult. This can vary depending on a number of factors including age, health, and drug interactions [38].
How to Take Levothyroxine?
Generally, levothyroxine should be taken with water 30 minutes to 1 hour before breakfast each day. This is done to prevent any potential interactions with food.
Levothyroxine should be taken 4 hours apart from drugs that may affect its absorption. Some examples include antacids, heartburn medications, and calcium carbonate supplements.
There’s some evidence that levothyroxine may be equally effective when taken at bedtime as well [39].
Brand vs. Generic
Not too long ago, different brands of levothyroxine were not interchangeable because they were not regulated by the FDA [6].
This is because thyroid extracts from animals were used for hypothyroidism since before the FDA was formed [6].
When levothyroxine was first developed, the FDA grouped levothyroxine with these animal thyroid extracts, which were not regulated [6].
It wasn’t until 1997 that the FDA decided to regulate thyroid medications, due to safety concerns from inconsistent products [6].
Today, drug standards have greatly improved. Most levothyroxine products are now compatible with each other (including brand and generics). However, some products are still not interchangeable [6].
Most experts typically recommend sticking with one form of levothyroxine if possible. If a change is necessary, lab tests are usually monitored more frequently until levels become stable again [6].
Takeaway
Levothyroxine is a synthetic form of the thyroid hormone T4. It is typically used to treat hypothyroidism. Less commonly, it is used for subclinical hypothyroidism, goiter, and thyroid cancer. Levothyroxine should not be used for weight loss. Side effects are usually mild and include headache, sleep problems, and weight changes.
