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 a factor.
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 be associated with it, and a functional medicine approach to this condition.
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What is Drug-induced Hypothyroidism
Drug-induced hypothyroidism is when the thyroid gland functions less actively 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 Affect Thyroid Function?
Understanding the hypothalamic-pituitary-thyroid (HPT) axis is essential to better understand how medications can influence thyroid function.
- 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, potentially affecting thyroid function.
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 may influence thyroid function.
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 May Be Associated with Drug-Induced Hypothyroidism
Iodine-Containing Medications
Iodine-containing medications and supplements may influence thyroid function through a phenomenon called the Wolff-Chaikoff effect, whereby ingesting a large dose of iodine affects thyroid hormone synthesis regardless of serum TSH levels. The most commonly prescribed of these medications is amiodarone, used to manage heart arrhythmias. (1)
Lithium
Lithium is used to manage bipolar disorder. Lithium may influence the release of thyroid hormones by increasing thyroidal iodine content and inhibiting the coupling of the building blocks to make thyroid hormones. (1)
Interleukin-2
Interleukin-2, used in the management of cancers, and Interferon-Alpha, used to manage hepatitis and various cancers, both may influence thyroid function 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, may influence thyroid function in more than 50% of cases. The etiology of TKI-induced effects on thyroid function 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 manage leukemia, melanoma, non-Hodgkin's lymphoma, Kaposi's Sarcoma, hepatitis C, hepatitis B, and human papillomavirus (HPV). Effects 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 interact with your thyroid gland. Up to 10% of patients on this medication may experience changes in thyroid function.
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 may influence TRH secretion, thereby affecting 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
- Addressing infertility in both men and women due to overproduction of prolactin.
- To help manage blood sugar levels in patients with type 2 diabetes.
- To address acromegaly (overproduction of growth hormone) and pituitary prolactinomas (tumors of the pituitary gland).
- Supports the management of 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 may influence TSH secretion. Finally, rexinoids, vitamin A derivatives used in the management of inflammatory skin conditions and skin cancers, appear to most significantly influence central hypothyroidism by affecting 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 manage tumors. They may influence changes in many different hormones throughout the body, including thyroid hormones. Up to 14% of people taking these medications may experience changes in thyroid function.
Hormone Medications
For those who are on thyroid replacement medications for the management 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 influence thyroid function 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 influence the body into a hypothyroid state, which may be managed by correcting dosage.
Functional Medicine Labs to Test for Hypothyroidism
If a patient is on any of these medications, it is suggested to monitor thyroid hormone levels about two months after starting the medication and then at least every six months to help ensure your thyroid is still functioning well.
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 may be elevated. In central hypothyroidism, TSH may 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 may 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 may indicate poor thyroid hormone conversion.
- Thyroid antibodies anti-TPO and anti-TG may 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 Managed?
Drug-induced hypothyroidism may be 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 management goals with drug-induced hypothyroidism are to support thyroid health and function, along with addressing symptoms associated with low thyroid hormones. This may include using either desiccated or synthetic thyroid replacement medications; however, natural options can be adjunctively implemented to support 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 may support healthy levels of inflammation in the body and reduce 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 may exert 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 may play 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 important in supporting thyroid health 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 may support 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 may help reduce oxidative stress, supporting overall health. Its combination of theanine and caffeine may help 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 mood-supporting properties. It also supports cardiovascular health and function, which may be beneficial for those 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 support thyroid levels in those with hypothyroidism.
Lifestyle changes
Stress reduction: Stress is a known factor that can influence the HPT axis by affecting TRH secretion and thyroid hormone production and may exacerbate hypothyroid symptoms. This study demonstrated that an eight-week stress management program may support 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 mood changes. Longer-term benefits include weight management, promotion of anti-inflammatory and immune pathways, and support for cardiovascular health.
Summary
Your medication may impact your thyroid gland function, potentially leading to 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 address hypothyroid symptoms.
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