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Avoiding Levothyroxine Side Effects: Why the Correct Diagnosis Matters

Written by Dr. Michael Ruscio, DC on November 1, 2021

Written by Dr. Michael Ruscio, DC on November 1, 2021 — Reviewed by Hilary Watts

Understanding Your Thyroid Lab Numbers Is Critical to Getting Proper Treatment

• Levothyroxine Side Effects|
• Thyroid Function 101|
• Reduce Your Risk|
• How to Take Thyroid Medication|
• Interpreting Thyroid Labs|
• The Bottom Line|

Levothyroxine sodium (brand names are Synthroid and Tirosint) is an FDA-approved prescription medication used to treat hypothyroidism. While this medication is incredibly effective for those who truly need it, we have people coming into the clinic at least once a week with levothyroxine side effects like 1 2:

• Dry mouth
• Fatigue
• Chest pain
• Hair loss
• Irregular heartbeat/palpitations
• Insomnia
• Skin rash/flushing
• Excessive sweating
• Nervousness
• Irritability
• Unexplained weight loss
• Menstrual irregularities

While the side effects we see are most often minor, we find these patients are either being medicated when they shouldn’t be or are being overmedicated for hypothyroidism. 

I want to make it clear that levothyroxine is very safe and effective for hypothyroidism when used appropriately. However, it’s being overprescribed, which has the potential to cause mild-to-serious side effects for people with subclinical hypothyroidism and those who are incorrectly diagnosed with hypothyroidism. That’s exactly what happened to one of my patients, and we’ll dig into her story a little later.

It’s not that practitioners aren’t well-intentioned, it’s just that misconceptions about healthy thyroid levels are rampant. Levothyroxine is often prescribed based on outdated practices and guidelines that are becoming less and less supported by research.

For example, a 2021 meta-analysis showed that around 30% of patients taking thyroid medication didn’t need to be taking it at all 3. Another found that 60% of patients were taking unnecessary thyroid medication and their thyroid hormone levels remained normal after discontinuation without a recurrence of hypothyroidism symptoms 4.

To clear up the confusion about hypothyroidism and levothyroxine, I’ll get into how overtreatment can create unwanted side effects, and what to do to avoid side effects if you truly need levothyroxine. I’ll also dive into thyroid basics, like testing, and how gut health factors into thyroid conditions and taking levothyroxine.

Potential Levothyroxine Side Effects

All drugs have potential side effects, some more serious than others. While levothyroxine side effects are rare when used properly, adding in thyroid hormone when little or none is needed can leave the patient feeling worse. Overmedicating someone with hypothyroidism can mimic symptoms of hyperthyroidism like irritability, weight loss, and difficulty sleeping. 

So, thyroid hormone replacement therapy isn’t something to be taken lightly or prescribed without a thorough assessment of blood work and other potentially confounding health issues. 

Here’s a chart of the potential negative levothyroxine side effects:

As you can see, levothyroxine can impact practically every body system. We will get into ways to reduce your risk of levothyroxine side effects, but first, let’s cover some thyroid basics. 

Thyroid Function 101

Your thyroid gland is a small, butterfly-shaped gland that wraps around your trachea at the front of your neck 7. As part of the endocrine system, it produces important hormones that help regulate 1 7:

• Energy production
• Digestive function
• Body weight
• Temperature
• Sex hormones
• Cardiovascular function
• Nervous system
• Fertility

When things go awry in your system as a result of autoimmunity, chronic/unmanaged stress, adverse drug reactions, and/or thyroid cancer, your thyroid gland can become inflamed (thyroiditis). Thyroiditis sometimes (but not always) precedes abnormal thyroid hormone production, which is typically classified into two categories:

• Hyperthyroidism: The thyroid gland produces too much thyroid hormone (overactive thyroid). Also referred to as Grave’s disease, when there is an autoimmune component. Hyperthyroidism can cause an enlarged thyroid (goiter) or nodules that are visible in your neck, in addition to eye protrusion (ophthalmopathy).
• Hypothyroidism: The thyroid gland isn’t producing enough thyroid hormone. This is often associated with an autoimmune disease called Hashimoto’s thyroiditis, but it isn’t the only cause of hypothyroidism 8.

Each of these thyroid problems can vary in seriousness, depending on just how low or high your thyroid hormone and antibody levels are. If a thyroid disorder goes untreated for a long time, major health problems can arise like heart disease (heart attack and stroke), adrenal issues (which can affect energy levels), infertility, unwanted weight gain or loss, sleep disorders, and cognitive issues.

So, as you can see, it’s very important to treat thyroid disorders promptly and appropriately. However, overmedicating or medicating someone who doesn’t need it can bring about its own set of problems and significantly affect their quality of life. Since levothyroxine is used to treat hypothyroidism, let’s dig deeper into this diagnosis and potential levothyroxine side effects. 

Hypothyroidism Basics

Your thyroid regulates so many important functions, so when it’s inflamed, you can experience a wide variety of symptoms. Both hypo- and hyperthyroidism can cause digestive dysfunction, fatigue, and sleep disturbances, but their other symptoms are quite different. I’ll focus on hypothyroidism here as it’s the most common thyroid condition, and it’s treated with levothyroxine and other thyroid medications.

Symptoms of hypothyroidism include 9 10 11 12 13 14:

• Fatigue
• Dry skin
• Mood swings
• Cold intolerance
• Hair loss
• Trouble swallowing
• Weight gain
• Constipation
• Muscle pain
• Hoarseness
• Shortness of breath
• Frontal neck pain
• Heart palpitations
• Vertigo
• Wheezing
• Irregular menstrual cycles
• Muscle cramps

Since a lot of these symptoms can occur gradually (and in the absence of a thyroid issue) the list of concerns can creep in without you or your healthcare provider realizing you have a thyroid problem. This is one reason regular blood testing is important. In addition, these symptoms may also be related to other conditions (like gut imbalances) that are far more common than hypothyroidism.

But symptoms alone aren’t specific or reliable enough to diagnose hypothyroidism. Blood testing is always necessary, and hypothyroidism is diagnosed when thyroid stimulating hormone (TSH) levels are high and free T4 levels are low. If you’re diagnosed with hypothyroidism, it’s likely you’ll be placed on thyroid hormone replacement like levothyroxine.

Reduce Your Risk of Levothyroxine Side Effects

As we saw above, 30-60% of people taking thyroid medication may not need it, and avoiding the use of unnecessary medication is the best way to prevent side effects. 

Overall, many studies show that overtreatment with levothyroxine is unlikely to be severely detrimental, which is great news 15 16 17 18 19 20. However, my concern is when people who don’t actually require thyroid medication are on it despite continuing to experience symptoms that they think are being caused by their thyroid. 

In these instances, true underlying conditions can go unnoticed and chronic symptoms can persist for years. So not only is the patient taking hormone therapy they don’t need placing them at risk for levothyroxine side effects, but their quality of life suffers tremendously. This happened to one of my patients who saw a “thyroid expert” that incorrectly diagnosed and treated her for hypothyroidism. Let’s take a look at her case.

When An Incorrect Diagnosis Can Worsen Symptoms

Before contacting the clinic, my patient sought treatment from another practitioner due to gas, bloating, fatigue, constipation, and diarrhea. She also had slight insomnia and some cramping during her menstrual cycle. Her thyroid labs were tested and she had a TSH of 1.8 (the normal range is 0.5–4.5) and a free T4 of 0.94 (normal range 0.7–1.9).

The provider diagnosed this patient with hypothyroidism (despite the fact that she had completely normal thyroid blood tests) and placed her on medication after medication. However, her symptoms continued to worsen. This by itself should have been a red flag that her thyroid wasn’t the cause of her symptoms. 

When she came to the clinic, we reviewed her history, symptoms, and previous lab results and rechecked her thyroid panel just to be sure it was indeed normal. I suspected the root cause of her symptoms to be gastrointestinal in nature, and we added simple gut-healing strategies like triple therapy probiotics and basic nutritional supplements, and she continued on her anti-inflammatory diet. After just 6 weeks, her symptoms had resolved. 

I share this case study to hammer home the point that gut issues are far more common than thyroid issues, and there are a variety of natural treatments for healing the gut that doesn’t place patients at risk for potentially serious side effects. 

In fact, we just published a case series and literature review in Integrative Medicine wherein we demonstrated how a gut-focused clinical care model can improve thyroid function, reduce thyroid medication dose, and improve symptoms originally thought to be from thyroid dysfunction. 

Subclinical Hypothyroidism and “Sluggish” Thyroid

If you’re in the subclinical hypothyroidism category where TSH levels are somewhat high but free T4 is normal, be wary of providers who want to add levothyroxine. This low-level issue doesn’t need to be treated with prescription drugs, and doing so could lead to levothyroxine side effects 21. 

While the research doesn’t suggest any severe issues related to levothyroxine use in subclinical hypothyroidism, it’s important to note that once levothyroxine is started for someone with subclinical hypothyroidism, they typically continue it indefinitely, which increases the risk of levothyroxine side effects and can be an unnecessary burden. 

In many cases, high TSH levels resolve on their own over time, especially if you take measures to optimize your sleep, reduce your stress, and improve your digestive health, as we’ve demonstrated in our case series.

In my experience, some ‘thyroid patients’ will discover that their TSH levels completely normalize once their gut issues have been treated, and they can discontinue thyroid medication. As a quick caveat, as you heal your gut, you more easily absorb medication and boost your natural thyroid function. This can lead to levothyroxine side effects over time, so have a doctor keep an eye on your labs and your symptoms while you continue to heal your gut and wean off your meds. 

Other patients that do need to continue with long-term medication can more easily optimize their dose of levothyroxine after healing their gut to reduce symptoms.

The research on the benefits of using levothyroxine in subclinical hypothyroidism is mixed. One observational study found adults with abnormal TSH levels who took levothyroxine long-term when they didn’t need it had an increased risk of heart disease and fractures 22. But older adults with subclinical hypothyroidism who were treated with levothyroxine had improved heart function and no negative bone health impact 23 24. 

Pregnant women with subclinical hypothyroidism who were given levothyroxine didn’t seem to benefit 25, but pre-menopausal women experienced significantly improved strength, mobility, and endurance performance 26.

One meta-analysis found that thyroid hormone therapy did not improve quality of life or thyroid-related symptoms in people with subclinical hypothyroidism 21. And a review found people over the age of 65 with subclinical hypothyroidism to be at increased risk of hyperthyroid symptoms when using levothyroxine 27. 

Unfortunately, levothyroxine is being overprescribed, and some providers even use this hormone therapy for people in the “sluggish” thyroid category (normal T4 and normal TSH levels with hypothyroid symptoms). I want to reiterate that levothyroxine should absolutely not be used in this instance and instead, there should be an investigation of the root causes of symptoms that mimic thyroid disorders.

How to Take Thyroid Medication to Avoid Side Effects

Levothyroxine (also known as LT4, T4, or thyroxine) is the synthetic form of the body’s natural T4 hormone, and it works to mimic/replace T4 production by the thyroid gland in order to restore important thyroid gland functions 1. 

If you need to take levothyroxine, you can feel confident that it’s safe and effective. The single most important thing you can do to avoid levothyroxine side effects is to get your labs checked regularly to prevent being overmedicated. For most, this will be every 3-4 months, but depending on your provider’s recommendations, it can vary up to once a year if you’re stable.

To avoid unnecessary side effects and to ensure maximum absorption, though, you do want to refer to the drug information packet and take this medication appropriately 1 28:

• Take tablet forms of levothyroxine on an empty stomach at least 30–60 minutes before breakfast or 3–4 hours after dinner. (Liquid and soft-gel capsule forms of levothyroxine may be taken with a meal).
• Avoid products that contain iron or calcium within 4 hours of taking levothyroxine.
• Do not take antacids or proton pump inhibitors at the same time you take tablet forms of levothyroxine.
• Consider separating fiber, soy, and coffee consumption by 1 hour.

It’s important to note that some prescription and over-the-counter (OTC) medications can interact with it. Here’s a list of some drugs that may impair levothyroxine absorption and reduce its effectiveness. Those with asterisks (*) need to be taken at least four hours apart from levothyroxine 29:

• Selective serotonin reuptake inhibitors (SSRIs)
• Calcium carbonate
• Ferrous sulfate*
• Orlistate
• Bile acid sequestrants (colesevelam, cholestyramine, colestipol)*
• Iron exchange resins (kayexalate, sevelmer)
• Proton pump inhibitors
• Sucralfate
• Antacids (aluminum and magnesium)*
• Hydroxides (simethicone)

In addition, there are drugs that can interact with levothyroxine and increase the risk of side effects 6 30:

• Estrogens and androgens (hormone replacement therapy)
• Tricyclic antidepressants
• Coumarin derivatives
• Warfarin
• Ketamine
• Sympathomimetics (like albuterol)

In addition to taking levothyroxine appropriately, you can speak with a well-informed healthcare professional about the use of Traditional Chinese Medicine if symptoms pop up while you and your doctor work on getting your dose dialed in. 

A 2022 meta-analysis of 9 randomized controlled trials found Yougui pills in combination with levothyroxine significantly reduced the side effects of levothyroxine when compared to taking levothyroxine alone 2. In these studies, the levothyroxine side effects that occurred most frequently included 2:

• Dry mouth
• Excessive sweating (hyperhidrosis)
• Insomnia
• Irritability 

Always seek medical advice from your doctor with regard to the other medications you’re taking before starting or stopping levothyroxine. This way, you’ll be aware of both potential side effects and contraindications (unwanted drug interactions).

How to Accurately Interpret Thyroid Labs

So how do you know if you should be taking levothyroxine? I mentioned blood work, and that really is the place to start. You need to know your baseline before taking any steps to address the symptoms that are leading you to believe you have a thyroid problem.

To determine whether or not you have optimal thyroid levels, you should ask your provider for the following blood work:

• TSH (thyroid-stimulating hormone)
• Free T4 (thyroxine)
• Free T3 (triiodothyronine)
• Thyroid antibodies (I won’t go into detail about this here, but read this for more detailed information, especially if you’re pregnant or planning to become pregnant).

You can also ask for a thyroid ultrasound, which can identify nodules and may be used as a diagnostic indicator.

TSH and free T4 blood values are needed to diagnose a thyroid disorder.  Before we review the specifics of each lab, this chart gives you an overview of how these labs are used to evaluate thyroid function 31 32:

*Reference ranges can vary based on your individual lab provider.

TSH

TSH is produced in the pituitary gland. A healthy range of TSH for a patient not taking levothyroxine is 0.45–4.5 IU/mL 33. This range can change if you’re pregnant or over 60 years old. If you’re taking levothyroxine, your level should be below 2.5 IU/mL 34. If TSH is too high, it could mean that your thyroid isn’t sufficiently utilizing TSH to create T4.

Free T4

T4 can be either free (available to use) or bound (bound to a protein and unusable). The ideal range for free T4 is 0.82–1.77 ng/dL. A number below this range (especially when paired with high TSH) indicates hypothyroidism, while a number above it (especially when paired with low TSH) indicates hyperthyroidism 31.

Free T3

You may have also heard of free T3, which can be either free form (active and available for use) or reverse form (inactive). The ideal range for free T3 is 2.0–4.4 pg/mL. While measuring T3 can give you some good information about your health, it’s not useful for diagnosing a thyroid disorder. Low levels of free T3 and high levels of reverse T3 indicate:

• Inflammation
• Potential digestive issues
• Signs of stress

If your T3 levels are off, it makes more sense to address gut health and/or adjust your levothyroxine levels if you’re truly hypothyroid, instead of taking the synthetic form of T3 (Liothyronine). T3 hasn’t been shown to improve hypothyroidism and can come with its own side effects 35.

If, after looking over your thyroid numbers, you find that you might need thyroid medication, then work with your doctor for a personalized plan. Keep in mind it’ll be important to monitor your TSH levels. Typically, when you start levothyroxine, the amount will be adjusted based on regular TSH measurements every 4–8 weeks until the dose is correct. Here’s more information on how to find your ideal thyroid medication.

Now let’s spend some time discussing why it’s so important to get an accurate diagnosis and clear up the confusion around subclinical hypothyroidism and “sluggish thyroid.”

Correct Diagnosis and Treatment Can Help You Avoid Levothyroxine Side Effects

Serious levothyroxine side effects are rare but mild ones can occur especially if you’re being medicated based on an incorrect diagnosis, are using this medication for subclinical hypothyroidism or “sluggish” thyroid. In cases like this, levothyroxine not only creates more problems than it solves, but it may also cover up other simple-to-fix medical conditions like gut health issues. 

If you require levothyroxine for overt hypothyroidism, taking your medication appropriately, avoiding drug interactions, and keeping track of your labs and symptoms will help prevent unwanted side effects.

If you’re experiencing the symptoms of hypothyroidism, it’s important to have your thyroid blood levels checked. If they’re normal, there’s no need to start levothyroxine or other thyroid medications. Gut health issues are likely a cause of your symptoms, so check out my step-by-step gut-healing guide in Healthy Gut, Healthy You.

If your thyroid levels are out of the normal ranges, think about signing up for our Thyroid Self-Management Program. This course is designed to reverse the underlying causes of thyroid dysfunction. You’ll use 4 powerful steps to heal your thyroid (these are the same steps that we use to help patients at our clinic, and that we’ve published in peer-reviewed medical journals).

The Ruscio Institute has developed a range of high-quality formulations to help our patients and audience. If you’re interested in learning more about these products, please click here. Note that there are many other options available, and we encourage you to research which products may be right for you.