What medications can cause transient thyroiditis in a 41-year-old female patient with hypothyroidism?

Medications That Can Cause Transient Thyroiditis

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors are the most clinically significant medications causing transient thyroiditis, occurring in 5-20% of treated patients. 1, 2

Mechanism and Clinical Pattern

• Anti-PD-1/PD-L1 agents (such as nivolumab and pembrolizumab) cause thyroid dysfunction in 6-9% of patients, while combination immunotherapy increases this risk to 16-20% 1, 3
• Ipilimumab causes hyperthyroidism in 12% and hypothyroidism in 18% of patients when combined with nivolumab 2
• The typical pattern is transient thyrotoxicosis (lasting 2-6 weeks) followed by permanent hypothyroidism in most cases 1, 4
• Thyroiditis from checkpoint inhibitors is usually transient and resolves within a couple of weeks, progressing to either primary hypothyroidism or normal thyroid function 1

Management Approach

• Monitor TSH and free T4 every 4-6 weeks from the start of immunotherapy for the first 3 months, then every second cycle thereafter 1
• During the hyperthyroid phase, use beta-blockers (atenolol or propranolol) for symptomatic relief rather than corticosteroids 1
• Corticosteroids are not usually required to shorten the duration of checkpoint inhibitor-induced thyroiditis 1
• Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption 1, 3
• Close monitoring every 2-3 weeks is essential to catch the transition from hyperthyroidism to hypothyroidism 1

Critical Safety Consideration

• Before initiating levothyroxine for hypothyroidism following checkpoint inhibitor therapy, always rule out concurrent adrenal insufficiency, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 1, 3

Amiodarone

Amiodarone causes thyroid dysfunction in 14-18% of patients through multiple mechanisms, including both destructive thyroiditis and iodine-induced effects. 5

Mechanisms of Thyroid Dysfunction

• Amiodarone inhibits peripheral conversion of T4 to T3 and releases large amounts of inorganic iodine 5
• It can cause either hypothyroidism (2-10% of patients) or hyperthyroidism (approximately 2% of patients) 5
• Amiodarone-induced hyperthyroidism poses a greater hazard than hypothyroidism due to the possibility of thyrotoxicosis and arrhythmia breakthrough, which may result in death 5

Clinical Recognition

• Hypothyroidism is identified by elevated serum TSH levels, though free thyroxine index values may be normal in some clinically hypothyroid patients 5
• Hyperthyroidism is identified by abnormally elevated serum T3, further elevations of serum T4, and subnormal TSH levels 5
• If any new signs of arrhythmia appear in patients on amiodarone, hyperthyroidism should be considered immediately 5

Management Strategy

• Thyroid function should be monitored prior to amiodarone treatment and periodically thereafter, particularly in elderly patients and those with thyroid nodules, goiter, or other thyroid dysfunction 5
• For hypothyroidism: manage by amiodarone dose reduction and/or thyroid hormone supplementation, though therapy must be individualized 5
• For hyperthyroidism: aggressive medical treatment is indicated, including dose reduction or withdrawal of amiodarone if possible, plus antithyroid drugs, beta-blockers, and/or temporary corticosteroid therapy 5
• Radioactive iodine therapy is contraindicated in amiodarone-induced hyperthyroidism due to low radioiodine uptake 5
• Amiodarone-induced hyperthyroidism may be followed by a transient period of hypothyroidism 5

Long-Term Considerations

• Because of slow elimination of amiodarone and its metabolites, high plasma iodide levels, altered thyroid function, and abnormal thyroid-function tests may persist for several weeks or even months following amiodarone withdrawal 5
• There have been postmarketing reports of thyroid nodules/thyroid cancer in patients treated with amiodarone 5

Other Medications Causing Transient Thyroiditis

Lithium

• Lithium can cause both hypothyroidism and transient thyrotoxicosis through destructive thyroiditis 6
• The mechanism involves interference with thyroid hormone synthesis and release 6

Interferon-Alpha

• Interferon-alpha causes thyroid dysfunction in approximately 5-10% of treated patients 6
• Can manifest as either destructive thyroiditis with transient hyperthyroidism or autoimmune thyroid disease 6

Tyrosine Kinase Inhibitors

• These agents can cause thyroid dysfunction through destructive thyroiditis or by affecting thyroid hormone metabolism 6

Distinguishing Transient from Permanent Thyroid Dysfunction

Key Diagnostic Features

• Transient thyroiditis typically presents with a non-tender thyroid gland, suppressed radioactive iodine uptake, normal white blood cell count, and normal erythrocyte sedimentation rate 7
• The natural history involves an initial thyrotoxic phase (2-6 weeks) followed by either recovery or progression to hypothyroidism 1, 4
• 30-60% of elevated TSH levels normalize spontaneously on repeat testing, highlighting the importance of not treating based on a single value 3, 8

Critical Pitfall to Avoid

• Failure to recognize transient hypothyroidism may lead to unnecessary lifelong treatment 3
• Always recheck TSH and free T4 after 3-6 weeks before committing to long-term levothyroxine therapy 3, 8
• Consider discontinuing levothyroxine in patients with drug-induced hypothyroidism where the offending medication has been discontinued and thyroid function has recovered 3

Special Populations

Pregnancy Considerations

• Women planning pregnancy who develop drug-induced thyroid dysfunction require immediate treatment, as untreated hypothyroidism increases risk of preeclampsia, low birth weight, and neurodevelopmental effects in offspring 1, 3
• Target TSH <2.5 mIU/L in the first trimester for pregnant women with any degree of thyroid dysfunction 3

Patients with Cardiac Disease

• In patients with cardiac disease or atrial fibrillation, drug-induced hyperthyroidism from transient thyroiditis requires urgent treatment with beta-blockers to prevent arrhythmia breakthrough 1, 5
• Start levothyroxine at lower doses (25-50 mcg/day) in elderly patients or those with cardiac disease when treating subsequent hypothyroidism 1, 3