What Medications Cause Low Thyroid Levels? A Comprehensive Guide

According to a 2015 study, the use of lithium has been associated with up to a five-fold increase in the risk of developing hypothyroidism. This phenomenon, where specific prescription drugs trigger an underactive thyroid, answers the question, 'what medications cause low thyroid levels?'.

Quick Summary

Several medications can cause low thyroid hormone levels, disrupting the gland's function through various mechanisms. Recognizing these drug-induced effects is vital for management and avoiding misdiagnosis.

Key Points

• Amiodarone and Lithium: These are two of the most common medications known to cause drug-induced hypothyroidism, with Amiodarone's high iodine content and Lithium's effect on hormone release being the primary mechanisms.

• Immunotherapy Risks: Cancer treatments like immune checkpoint inhibitors can trigger autoimmune thyroiditis, which often leads to a phase of hyperthyroidism followed by permanent hypothyroidism.

• Cancer Drug Effects: Specific tyrosine kinase inhibitors used in cancer therapy, such as Sunitinib, frequently cause hypothyroidism by damaging the thyroid or interfering with iodine uptake.

• Drug Interactions with Levothyroxine: For patients on pre-existing thyroid hormone replacement, medications like Proton Pump Inhibitors or certain anticonvulsants can interfere with absorption or increase metabolism, necessitating dose adjustments.

• Proactive Monitoring is Crucial: Regular monitoring of TSH levels is essential for patients on high-risk medications, allowing for early detection and management of drug-induced thyroid dysfunction.

• Management is Possible: In most cases, patients can continue their critical medication while receiving thyroid hormone replacement therapy to manage hypothyroidism.

Understanding Drug-Induced Hypothyroidism

Drug-induced hypothyroidism occurs when certain medications interfere with the body's thyroid function, leading to a deficiency in thyroid hormones. While many associate hypothyroidism with autoimmune disease, medication is a significant and often overlooked cause. These drug-related effects can manifest through several pathways, including interfering with hormone synthesis, damaging thyroid tissue, altering hormone metabolism, or suppressing the central regulatory system involving the pituitary gland. Recognition of these effects is crucial for proper diagnosis and management, as the symptoms (fatigue, weight gain, cold intolerance) can significantly impact a patient's quality of life.

Medications That Affect Thyroid Hormone Synthesis and Release

Amiodarone (Pacerone, Nexterone)

• Mechanism: Amiodarone is a class III antiarrhythmic drug used to treat abnormal heart rhythms. It is a potent inducer of thyroid dysfunction due to its high iodine content (37% by weight), which can interfere with thyroid hormone synthesis through the Wolff-Chaikoff effect. Amiodarone also directly inhibits the conversion of the less-active thyroxine (T4) into the more-active triiodothyronine (T3) and can cause destructive thyroiditis.
• Clinical Impact: Amiodarone-induced hypothyroidism is more common in iodine-sufficient populations and in patients with underlying autoimmune thyroid disease. Monitoring of thyroid function tests (TSH, free T4) is essential at baseline and during treatment.

Lithium

• Mechanism: Used to treat bipolar disorder, lithium can inhibit the release of thyroid hormones from the thyroid gland. It also interferes with iodine metabolism and can cause goiter (thyroid enlargement).
• Clinical Impact: Hypothyroidism develops in about 20% of patients taking lithium, with women being at higher risk. While goiter is more common, hypothyroidism often requires treatment with levothyroxine. Lithium can increase pre-existing thyroid autoimmunity.

Medications Causing Thyroiditis and Autoimmunity

Immune Checkpoint Inhibitors (ICIs)

• Mechanism: These cancer immunotherapies (e.g., Pembrolizumab, Nivolumab, Ipilimumab) work by boosting the immune system's attack on cancer cells. A side effect is the activation of the immune system against healthy tissues, including the thyroid, leading to thyroiditis. The typical pattern is a temporary period of hyperthyroidism as thyroid cells are destroyed, followed by permanent hypothyroidism.
• Clinical Impact: Thyroid dysfunction is a common immune-related adverse event with ICIs, particularly PD-1/PD-L1 inhibitors. Regular monitoring of TSH and free T4 is crucial, as the onset can be sudden.

Interferon-Alpha

• Mechanism: This medication, used for conditions like hepatitis C and some cancers, can trigger an autoimmune-mediated destructive thyroiditis. Like ICIs, this can lead to a biphasic thyroid dysfunction with an initial hyperthyroid phase.

Medications Affecting Thyroid Hormone Metabolism and Absorption

Tyrosine Kinase Inhibitors (TKIs)

• Mechanism: Several TKIs, including Sunitinib and Sorafenib, used to treat various cancers, can cause hypothyroidism. Mechanisms include inhibition of iodine uptake by the thyroid, potential damage to thyroid vascularization, and drug-induced thyroiditis. Some TKIs also affect peripheral thyroid hormone metabolism by interfering with deiodinases.
• Clinical Impact: The incidence of hypothyroidism with sunitinib can be significant (over 50%). Regular thyroid function testing is recommended for patients on these therapies.

Anticonvulsants

• Mechanism: Drugs like Phenytoin and Carbamazepine can increase the hepatic metabolism of thyroid hormones, accelerating their clearance from the body. Valproic acid has been linked to increased TSH levels in children.
• Clinical Impact: Patients receiving thyroid replacement therapy may require dose adjustments when starting or stopping these anticonvulsants.

Proton Pump Inhibitors (PPIs)

• Mechanism: PPIs (e.g., Omeprazole) reduce stomach acid, which can decrease the absorption of oral levothyroxine.
• Clinical Impact: Patients on PPIs and levothyroxine may need a higher dose of levothyroxine or should be advised to take the medications several hours apart.

Methimazole and Propylthiouracil (PTU)

• Mechanism: These are ironically used to treat hyperthyroidism by blocking hormone synthesis. Excessive dosing can cause iatrogenic (treatment-induced) hypothyroidism.

Comparison of Key Drug Classes Causing Hypothyroidism

Medication Class	Examples	Primary Mechanism of Action	Special Considerations
Antiarrhythmics	Amiodarone	Iodine-induced synthesis inhibition; T4-T3 conversion block; destructive thyroiditis	High iodine load; effects can persist long after discontinuation
Psychotropic Drugs	Lithium	Inhibits thyroid hormone release; goiter inducement	Higher risk in women and older patients; can worsen pre-existing autoimmunity
Immunotherapy	Checkpoint Inhibitors (Nivolumab, Pembrolizumab)	Autoimmune destructive thyroiditis	Often preceded by a phase of hyperthyroidism; requires permanent hormone replacement
Cancer Therapies	Tyrosine Kinase Inhibitors (Sunitinib, Sorafenib)	Inhibition of iodine uptake; destructive thyroiditis; altered hormone metabolism	Routine TSH monitoring is recommended due to high incidence
Anticonvulsants	Phenytoin, Carbamazepine	Increases metabolic clearance of T4	May require levothyroxine dose adjustments in existing hypothyroid patients
Antithyroid Drugs	Methimazole, PTU	Blocks hormone synthesis	Iatrogenic hypothyroidism from over-treatment; dose-dependent effect
Stomach Acid Reducers	Proton Pump Inhibitors (Omeprazole)	Decreases levothyroxine absorption	Significant for patients on existing hormone replacement therapy

Management and Monitoring

For patients starting or taking medications known to affect thyroid function, consistent monitoring is essential. This often involves baseline and regular follow-up measurements of thyroid-stimulating hormone (TSH) and free T4.

• Baseline Testing: Before initiating treatment with high-risk drugs like amiodarone, lithium, or ICIs, doctors should conduct baseline thyroid function tests. Testing for thyroid antibodies (e.g., anti-TPO) can identify patients with pre-existing autoimmunity who may be at greater risk.
• Regular Monitoring: The frequency of monitoring varies by drug but often includes checks every few weeks or months, especially early in treatment.
• Treatment: In many cases, if hypothyroidism develops, the offending medication does not need to be stopped. Instead, thyroid hormone replacement therapy with levothyroxine is initiated to normalize hormone levels. Higher doses of levothyroxine may be required when using certain drugs that affect metabolism or absorption.

Conclusion

Drug-induced hypothyroidism is a significant clinical issue that can arise from a wide range of medications, each with a unique mechanism of action. The key to effective management lies in a high index of suspicion, proactive monitoring of thyroid function, and awareness of specific drug-thyroid interactions. While medication-related hypothyroidism can often be managed with hormone replacement therapy, it underscores the importance of close collaboration between different medical specialties, especially endocrinologists, cardiologists, oncologists, and psychiatrists. This collaborative approach ensures that patients continue to receive necessary treatment for their primary condition while effectively managing and mitigating the risk of thyroid dysfunction.

NEJM - Drug Effects on the Thyroid

Frequently Asked Questions

Which medications are most likely to cause hypothyroidism?

Among the most likely medications to cause hypothyroidism are Amiodarone (for heart rhythm issues), Lithium (for mood disorders), immune checkpoint inhibitors (for cancer), and certain tyrosine kinase inhibitors (also for cancer).

How do immune checkpoint inhibitors cause hypothyroidism?

Immune checkpoint inhibitors can cause an autoimmune attack on the thyroid gland, leading to thyroiditis. This inflammation typically causes a biphasic pattern: a temporary phase of hyperthyroidism as stored hormones are released, followed by a permanent state of hypothyroidism.

Is drug-induced hypothyroidism permanent?

The permanence of drug-induced hypothyroidism depends on the specific medication and mechanism. For example, hypothyroidism caused by immune checkpoint inhibitors is often permanent, while some cases related to Amiodarone or other drugs can resolve after discontinuation, though it may take months due to the long half-life of some drugs.

Can drugs interfere with my existing thyroid hormone replacement?

Yes, certain drugs can interfere with the absorption or metabolism of levothyroxine. Examples include Proton Pump Inhibitors, calcium supplements, iron supplements, and anticonvulsants like Phenytoin. It is important to take levothyroxine on an empty stomach and separate it from other medications by several hours.

What are the symptoms of drug-induced hypothyroidism?

The symptoms are the same as any other form of hypothyroidism and include fatigue, weight gain, increased sensitivity to cold, constipation, dry skin, and depression. These symptoms may be subtle and develop slowly over time.

What should I do if I think my medication is affecting my thyroid?

If you suspect your medication is causing thyroid problems, contact your healthcare provider immediately. They will perform blood tests (TSH, free T4) to check your thyroid function. Never stop taking a prescribed medication without consulting your doctor first.

Do I need to stop my medication if it causes hypothyroidism?

In most cases, no. Your doctor will likely continue the essential medication and treat the hypothyroidism with a thyroid hormone replacement, such as levothyroxine. The benefits of continuing the primary treatment often outweigh the risks, as the thyroid side effect can be managed.