The thyroid gland is butterfly-shaped and located in the front of the neck. It plays a significant role in the human body's metabolism, growth, and development. It does this by constantly releasing a steady amount of thyroid hormones into the bloodstream. If you experience symptoms like fatigue, depression, cold intolerance, and constipation, underlying hypothyroidism may be to blame.

There are several reasons why hypothyroidism can occur. One less discussed reason is the side effect of medications. This article will discuss drug-induced hypothyroidism, what medications are known to cause it, and a functional medicine approach to this diagnosis.

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What is Drug-induced Hypothyroidism

Drug-induced hypothyroidism is the under activity of the thyroid gland due to a side effect from a medication.

Common signs and symptoms of hypothyroidism include:

• Fatigue
• Increased sensitivity to cold
• Constipation
• Dry skin
• Hair loss
• Brain fog
• Depression
• Thinning of the outer third of the eyebrows
• Unintentional weight gain

How Do Some Medications Cause Hypothyroidism?

Understanding the hypothalamic-pituitary-thyroid (HPT) axis is essential to understand better how medications can cause hypothyroidism.

• When the brain receives a signal that circulating thyroid hormone levels are low, two things happen: first, the hypothalamus releases thyrotropin-releasing hormone (TRH); this stimulates the anterior pituitary gland to produce thyroid-stimulating hormone (TSH).
• TSH acts on the thyroid gland to induce the synthesis and release of thyroid hormones: predominantly thyroxine (T4), with some triiodothyronine (T3).
• T4 is the inactive form of thyroid hormone, and it travels throughout the body and is converted to activated T3 when needed.
• During times of physiologic stress, T4 may convert to a largely inactive form of thyroid hormone called reverse T3 (rT3).
• T4 and T3 in circulation exert negative feedback to the brain, decreasing the release of TRH and TSH and preventing the overproduction of thyroid hormones.
  

Certain medications can interfere at various levels along this axis, causing hypothyroidism.  

Primary hypothyroidism occurs at the level of the thyroid. Medications can inhibit the synthesis or release of thyroid hormones, generate inflammation within the gland (called thyroiditis), and induce thyroid autoimmunity.

Central hypothyroidism occurs at the level of the brain. Medications that impede healthy TRH or TSH signaling will cause hypothyroidism.

For those with pre-existing hypothyroidism, certain medications can interact with treatment by decreasing absorption or altering the transport and metabolism of replacement thyroid hormones. This can necessitate an increased thyroid replacement dosage. (1)

11 Medications That Can Cause Drug-Induced Hypothyroidism

Iodine-Containing Medications

Iodine-containing medications and supplements exert hypothyroid effects through a phenomenon called the Wolff-Chaikoff effect, whereby ingesting a large dose of iodine shuts down thyroid hormone synthesis regardless of serum TSH levels. The most commonly prescribed of these medications is amiodarone, used to treat heart arrhythmias. (1)

Lithium

Lithium is used to treat bipolar disorder. Lithium blocks the release of thyroid hormones by increasing thyroidal iodine content and inhibits the coupling of the building blocks to make thyroid hormones. (1)

Interleukin-2

Interleukin-2, used in the treatment of cancers, and Interferon-Alpha, used to treat hepatitis and various cancers, both induce hypothyroidism by inducing immune pathways favoring an inflammatory state, resulting in either autoimmune or non-autoimmune thyroiditis. (1, 2)

Tyrosine Kinase Inhibitors (TKIs)

Tyrosine Kinase Inhibitors (TKIs), also an anticancer drug, will induce hypothyroidism in more than 50% of cases. The etiology of TKI-induced hypothyroidism is multifactorial but includes induction of thyroidal inflammation and upregulation of thyroid hormone metabolism by the liver. (1)  

Interferon Alfa

Interferon alfa is used to treat leukemia, melanoma, non-Hodgkin's lymphoma, Kaposi's Sarcoma, hepatitis C, hepatitis B, and human papillomavirus (HPV). Affects on thyroid function have been seen after three months of taking this medication. In addition to causing thyroiditis, this medication prompts your body to make antibodies that fight your thyroid gland. Up to 10% of patients on this medication end up with hypothyroidism.

Glucocorticoids

Central hypothyroidism can result from taking multiple medications. Glucocorticoids are commonly prescribed for inflammatory health conditions and Addison's disease (adrenal insufficiency). This class of drug inhibits TRH secretion, thereby decreasing serum TSH and thyroid function.

Bromocriptine

Bromocriptine belongs to the group of medicines known as ergot alkaloids and has been shown to reduce serum TSH levels. Bromocriptine blocks the release of a hormone called prolactin from the pituitary gland and is used for multiple reasons, including:

• Managing amenorrhea
• Treating infertility in both men and women due to overproduction of prolactin.
• To lower blood sugar levels in patients with type 2 diabetes.
• To treat acromegaly (overproduction of growth hormone) and pituitary prolactinomas (tumors of the pituitary gland).
• Treats the signs and symptoms of Parkinson's disease, often in combination with levodopa.
  

Somatostatin Analogues

Somatostatin analogues like octreotide, prescribed for acromegaly and certain tumors, also directly inhibit TSH secretion. Finally, rexinoids, vitamin A derivatives used in the treatment of inflammatory skin conditions and skin cancers, appear to most significantly induce central hypothyroidism by directly inhibiting TSH secretion by the pituitary. (3)

Checkpoint Inhibitors

Checkpoint inhibitors are a type of immunotherapy that block immune checkpoint proteins from binding with partner proteins and are used to fight tumors. They cause changes in many different hormones throughout the body, including thyroid hormones. Up to 14% of people taking these medications had hypothyroidism.

Hormone Medications

For those who are on thyroid replacement medications for the treatment of hypothyroidism, exogenous estrogens in the form of estrogen replacement therapy and oral contraceptives can increase the concentration of thyroxine-binding globulin (TBG). TBG binds thyroid hormones to carry them through circulation, which renders them inactive. A higher TBG concentration can exacerbate hypothyroidism by creating a higher concentration of bound/inactive hormones.

Hyperthyroid Medications

Methimazole and propylthiouracil are antithyroid medications prescribed for hyperthyroidism (overactive thyroid). If these medications are not monitored and adjusted accordingly, they can throw the body into a hypothyroid state, easily reversible by correcting dosage.

Functional Medicine Labs to Test for Hypothyroidism

If a patient is on any of these medications, it is recommended to monitor thyroid hormone levels about two months after starting the medication and then at least every six months to ensure your thyroid is still healthy.

Comprehensive Thyroid Panel

To assess the state of thyroid function, a Complete Thyroid Panel including thyroid-stimulating hormone (TSH), T3 (free and total), T4 (free and total), reverse T3, and thyroid peroxidase (TPO) and anti-thyroglobulin (TG) and antibodies should be assessed using functional medicine ranges.

• TSH is the most common test ordered to monitor thyroid function, especially in the conventional setting. In primary hypothyroidism, TSH will be elevated. In central hypothyroidism, TSH will be suppressed.  ‍
• Free T4 and Free T3 are the portions of thyroid hormones that are unbound to proteins in serum and available to bind to cell receptors and exert their effects in the body. In overt hypothyroidism, one or both of these will be low.  ‍
• Total T4 and Total T3 measures both free and bound thyroid hormone and quantifies the total hormone level made by the thyroid. Comparing these levels to the free portions can help to deduce the percentage of thyroid hormone that is being bound and inactivated. TBG can be measured if needing additional markers to distinguish abnormal thyroid function tests due to abnormal thyroid production versus changes in TBG concentrations.
• Comparing reverse T3 to free T4 and free T3 helps understand thyroid hormone conversion. A low free T3-to-reverse T3 ratio indicates poor thyroid hormone conversion.  
• Thyroid antibodies anti-TPO and anti-TG will be elevated in autoimmune hypothyroidism. They are often present prior to changes in TSH and thyroid hormones.

Inflammatory Markers

C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) are the two markers that quantify inflammation and would be expected to be elevated in cases where inflammation is contributing to reduced thyroid function.

Micronutrients

Thyroid health and function require many vitamins and minerals. Ordering a micronutrient panel helps analyze the nutritional status to identify suboptimal or deficient nutrient levels that may be contributing to thyroid dysregulation.

How Is Drug-Induced Hypothyroidism Treated?

Drug-induced hypothyroidism is reversible if the initiating medication is discontinued. But you should always consult with and work with your doctor before discontinuing or reducing medication dosage as it may not be safe for your current condition or feasible at that time.

In the meantime, the treatment goals with drug-induced hypothyroidism are to support thyroid health and function, along with mediating symptoms caused by low thyroid hormones. This may include using either desiccated or synthetic thyroid replacement medications; however, natural options can be adjunctively implemented to increase treatment success and potentially decrease dependence on thyroid replacement therapy.

Nutrition

The Mediterranean diet focuses on the frequent consumption of fruits and vegetables, lean protein, and unsaturated fats. This way of eating supports healthy levels of inflammation in the body and reduces oxidative stress on a cellular level. Diets like these have been shown to improve nutritional markers specific to the thyroid's needs, optimize thyroid function on lab findings, and reduce hypothyroid symptoms. (4, 5, 6)

Eating a gluten-free diet is correlated with improved thyroid markers and exerts a protective effect against autoimmune disease.

Herbs & Supplements

Don't be fooled by the many over-the-counter supplements containing iodine marketed to support thyroid function. Iodine is required for thyroid hormone synthesis, and frank iodine deficiency can contribute to hypothyroidism. However, in iodine-replete areas of the world (including the United States), iodine-deficiency hypothyroidism is extremely rare, and supplementation exceeding nutritional needs can lead to hypothyroidism. The literature supports avoidance of iodine supplementation, and some research even suggests iodine restriction results in improved markers of thyroid function.  

Vitamin D: plays a crucial role in immune system modulation and directly shifts immune pathways away from pro-inflammatory responses and promotes anti-inflammatory ones. This study confirmed the association between vitamin D deficiency and the development of autoimmune hypothyroidism. It concluded that vitamin D supplementation plays a beneficial role in decreasing the risk of hypothyroidism.

Selenium: is an essential micronutrient utilized as a cofactor in synthesizing and activating thyroid hormones. Overwhelmingly, the research suggests that maintaining adequate selenium levels is critical in preventing thyroid disease by its mechanisms involved in reducing autoimmune proteins, preserving the anatomical structure of the thyroid, and optimizing the quality of life.

Myo-Inositol: is a sugar compound that mediates hormonal cell signaling, among other functions. Supplementing myo-inositol in conjunction with selenium results in lowered TSH levels, a sign of normalization of thyroid function, and a decline in anti-thyroid antibodies in autoimmune thyroiditis.

Green tea: has many documented health benefits and can be used to address the symptoms of hypothyroidism. Its wide array of antioxidant compounds combats oxidative stress, reducing inflammation in the body. Its combination of theanine and caffeine helps to boost energy levels and focus without causing anxiety, which often comes alongside caffeine.  

Cordyceps: is an adaptogenic mushroom that has been shown to have anti-inflammatory, anti-fatigue, and antidepressant properties. It also supports cardiovascular health and function, mitigating the risk of heart disease associated with hypothyroidism.

Ashwagandha Root Extract: is commonly used in integrative medicine to support thyroid function. Research is limited on this adaptogen, but the current studies show Ashwagandha may improve thyroid levels in those with hypothyroidism.

Lifestyle changes

Stress reduction: Stress is a known factor that disrupts the HPT axis by blunting TRH secretion and downregulating thyroid hormone production and can exacerbate hypothyroid symptoms. This study demonstrated that an eight-week stress management program improved thyroid function markers and quality of life.

Sleep Hygiene: Sleep is vital for the maintenance of mental and physical health. If your hypothyroidism is causing insomnia, it is essential to form healthy sleep hygiene habits to optimize sleep quality. Following a nighttime routine, unplugging electronics in the evening, and keeping the bedroom dark and calm can help promote deep sleep. Talk with your doctor about ruling out sleep apnea if you snore loudly, wake often throughout the night, or feel tired upon waking. Sleep apnea has been associated with a higher prevalence and severity of thyroid autoimmunity.

Exercise: Regular physical activity provides a multitude of health benefits. Immediate effects of exercise may include improved energy, clearer thinking, and less severe depression. Longer-term benefits include weight management, promotion of anti-inflammatory and immune pathways, and prevention of cardiovascular disease.

Summary

Your medication may impact your thyroid gland function, causing drug-induced hypothyroidism. Discontinuation of the inciting medication may not be plausible, but there are effective options in addition to thyroid replacement therapy to support thyroid health and palliate hypothyroid symptoms.