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What Are the Long-Term Side Effects of Levothyroxine?

Key Takeaways

Overtreatment with levothyroxine, a medication used to treat hypothyroidism, can have long-term side effects like cardiovascular issues, worsening blood glucose control, and decreased bone mineral density. 

Levothyroxine is a prescription medication that is used to treat hypothyroidism (an underactive thyroid gland) when the thyroid gland doesn’t make enough thyroid hormone. But like many medications, levothyroxine can also cause some unwanted effects. Please continue reading to learn more about the short- and long-term side effects of levothyroxine therapy.

What is the downside to taking levothyroxine?

The downside of taking levothyroxine is that it can cause side effects. Most of these side effects are temporary and go away once your body adjusts to the medicine. Some of the short-term side effects of levothyroxine include:

  • Nausea

  • Vomiting

  • Diarrhea

  • Increase in appetite

  • Weight changes

  • Headache

  • Restlessness

  • Problems sleeping

  • Flushing

  • Sweating 

  • Fever

  • Sensitivity to heat

  • Changes in menstrual cycle

  • Leg cramps

  • Muscle cramps

  • Shakiness, especially in the hands

  • Joint pain

  • Hair loss

Tell your healthcare professional if these side effects are severe or do not go away after some time.

What are the long-term side effects of levothyroxine? 

Cardiovascular Risks

Levothyroxine can lead to an increase in heart rate, chest pain (angina), and irregular heartbeat (arrhythmias or heart rhythm abnormalities). This side effect can make you feel like your heart is pounding or racing. The risk of these adverse effects is higher in elderly patients and people with pre-existing heart disease. 

Tell your doctor if you have a history of cardiovascular disease, including coronary artery disease and myocardial infarction (heart attack). Your doctor may start you on a lower dose of levothyroxine and monitor you carefully with blood tests. If you develop heart symptoms, you may need to lower your levothyroxine dose or discontinue treatment temporarily and restart at a lower dose. You may also be advised to cut down your caffeine intake to help improve this side effect.

Worsening Blood Glucose Control

Levothyroxine can lead to worsening glycemic control (blood sugar control) in diabetic patients being treated with certain medications. While levothyroxine does not directly increase your blood glucose, it can interact with certain diabetic medications and make it less effective. You may need to increase the dose of your oral diabetes medications or insulin while on levothyroxine. Talk to your doctor about how often you should monitor blood glucose levels. 

Decreased Bone Mineral Density

Long-term treatment with levothyroxine can lead to increased bone resorption and decreased bone mineral density, especially in post-menopausal women. This can result in changes in certain blood tests, such as increased blood levels and increased urinary elimination of calcium and phosphorus, elevations in bone alkaline phosphatase, and decreased serum parathyroid hormone levels. To lower the risk of osteoporosis, your doctor will give you the lowest dose of levothyroxine needed to treat your hypothyroidism symptoms. 

What are the serious risks of taking levothyroxine?

Serious Allergic Reactions

Rarely, taking levothyroxine can cause a severe allergic reaction, including anaphylaxis (throat closing) and serious skin reactions. Call your health care professional immediately or seek emergency medical attention if you develop the following symptoms:

  • Skin rash, hives, skin itching, peeling, blistering, or flushing

  • Swelling of the eyes, face, lips, tongue, throat, hands, lower legs, ankles, or feet

  • Difficulty breathing or swallowing

  • Shortness of breath

  • Hoarseness

  • Severe stomach pain or nausea

Weight Loss

Weight gain is one of the symptoms of hypothyroidism (underactive thyroid). Treatment with levothyroxine can help people with hypothyroidism lose weight by treating the underlying condition. However, this medication should not be used to treat obesity or cause weight loss. In euthyroid patients (people with normal thyroid function), the typically prescribed doses of levothyroxine do not result in weight reduction. Taking high doses of levothyroxine for weight loss can lead to serious, even life-threatening toxicity, especially when used with certain other weight loss medications. Check out our blog to learn the difference between an underactive vs overactive thyroid.

Drug Interactions

Taking levothyroxine with certain other medications, for example, amphetamines (medications used to treat attention deficit hyperactivity disorder ADHD), can result in serious or even life-threatening problems. 

Call your doctor immediately or seek emergency medical care if you develop symptoms such as chest pain, rapid or irregular heartbeat, anxiety, irritability, nervousness, uncontrolled shaking, sleep problems, excessive sweating, or shortness of breath.

Narrow therapeutic index 

Levothyroxine is a narrow therapeutic index (NTI) drug, meaning small differences in the dose or blood concentration of this medication can result in therapeutic failure when the condition is not being adequately treated or in the potential worsening of adverse reactions.

Your doctor will adjust your dose of levothyroxine carefully and monitor thyroid stimulating hormone (TSH) levels to prevent overtreatment or undertreatment. Follow your doctor’s dosing instructions carefully. Keep all your lab and medical appointments. 

Also, give your doctor a complete list of your other medications to avoid potentially dangerous drug interactions with your thyroid medication. Check with your doctor before starting any new medication while on levothyroxine. 

Myxedema Coma

Myxedema coma is a rare, potentially fatal complication of severe hypothyroidism (underactive thyroid gland). It results in slowed functioning of multiple organs in the body and is a medical emergency. 

In people with myxedema coma, the absorption of levothyroxine from the gut can be unpredictable. Therefore, oral thyroid hormone replacement products such as levothyroxine are not used to treat this life-threatening condition. Instead, doctors use intravenous thyroid hormone products (by injection) to treat myxedema coma. 

Risk in Patients with Adrenal Insufficiency

Adrenal insufficiency is a condition in which the adrenal glands do not make enough of certain hormones such as cortisol and aldosterone (glucocorticoids). Thyroid hormone increases the elimination of glucocorticoids from the body. Therefore, starting thyroid hormone replacement with levothyroxine therapy before starting glucocorticoid replacement therapy can trigger an acute adrenal crisis in people with adrenal insufficiency. Tell your doctor if you have a history of adrenal gland problems before starting levothyroxine for thyroid disease. 

What is the greatest risk of long-term levothyroxine?

The greatest risks of long-term treatment with levothyroxine are: 

  • An increased risk of heart disease, especially in older adults and people with pre-existing heart conditions.

  • An increased risk of osteoporosis and bone fractures, especially in post-menopausal women and elderly patients above 70 years of age. 

  • Worsening blood glucose control in people with diabetes.

  • Overtreatment or undertreatment of thyroid disease if thyroid hormone levels are not carefully monitored.

How does levothyroxine work?

Levothyroxine is the synthetic form of a natural thyroid hormone called thyroxine (T4). It is given as a replacement for people whose bodies don’t make enough T4. Low thyroid hormone levels in the body are called hypothyroidism or underactive thyroid gland. 

Hypothyroidism can cause symptoms such as extreme fatigue, weight gain, cold intolerance, muscle and joint pain, dry skin, thinning hair, slowed heart rate, heavy or irregular menstrual periods, fertility problems, and depression. Check out 8 signs you may have a thyroid condition.

By replacing thyroid hormones, levothyroxine relieves these symptoms and helps to maintain normal thyroid function.

Can levothyroxine cause cancer?

Studies have found that taking levothyroxine long-term is associated with a slightly increased cancer risk in both men and women, including an increased risk of breast cancer, lung cancer, gastrointestinal cancers (stomach, colon, liver, pancreas), urinary bladder, skin, and thyroid cancer.

Note: If your thyroid gland has been surgically removed (thyroidectomy) as a treatment for thyroid cancer, your body will no longer make thyroid hormones, and you will need to take thyroid hormone replacement (levothyroxine) to maintain normal thyroid function.

Is it safe to take levothyroxine long term?

It is generally safe to take levothyroxine long-term as prescribed by a doctor. Hypothyroidism is a lifelong condition, so you will likely need to take levothyroxine for life. Your doctor will prescribe the lowest dose of levothyroxine to control your symptoms. Follow your doctor’s dosing instructions carefully and keep all your medical and lab appointments during levothyroxine treatment.

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References:

  1. https://medlineplus.gov/druginfo/meds/a682461.html

  2. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e95720f2-91c9-a6d0-f7d5-8bcb94d07bbc#:

  3. https://www.nhs.uk/medicines/levothyroxine/

  4. https://www.ncbi.nlm.nih.gov/books/NBK545193/

  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084377/#:~

  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052136/

  7. https://www.cancer.org/cancer/types/thyroid-cancer/treating/thyroid-hormone-therapy.html#

  8. https://pubmed.ncbi.nlm.nih.gov/33793038/

  9. https://www.sciencedirect.com/science/article/abs/pii/S1877782120300412#: