What is the proper usage of Propylthiouracil (PTU) in treating hyperthyroidism?

Propylthiouracil Use in Hyperthyroidism

Primary Recommendation

Propylthiouracil (PTU) should be reserved as a second-line agent for hyperthyroidism, used only when methimazole is not tolerated or contraindicated, due to PTU's significant risk of severe hepatotoxicity including liver failure and death. 1

Indications for PTU Use

PTU is indicated specifically for: 1

• Graves' disease or toxic multinodular goiter when patients are intolerant to methimazole and surgery or radioactive iodine are not appropriate options 1
• Preparation for thyroidectomy or radioactive iodine therapy in methimazole-intolerant patients 1
• First trimester of pregnancy or just before conception when an antithyroid drug is needed, as PTU may be preferred over methimazole during this specific period 2, 1

Dosing Regimen

Initial dosing: PTU is typically administered at 300 mg daily, divided into three doses (every 8 hours) 1, 3

• The three-times-daily dosing is necessary because PTU has a shorter half-life than methimazole 1
• Goal: Maintain Free T4 in the high-normal range using the lowest effective dose 2

Monitoring schedule: 2

• Check thyroid function tests every 2-4 weeks initially to adjust dosage 2
• Continue monitoring every 2-3 weeks, watching for transition to hypothyroidism 2

Critical Safety Monitoring

Black box warnings require vigilance for: 1

• Severe hepatotoxicity: Monitor for fever, loss of appetite, nausea, vomiting, right upper quadrant pain, dark urine, pale stools, jaundice, or itching 1
• Agranulocytosis: Usually occurs within first 3 months; monitor for fever, chills, or sore throat 1
• Vasculitis: Can affect skin, kidneys, or lungs and may be life-threatening 1

Stop PTU immediately if any signs of liver injury or serious adverse effects appear 1

Adjunctive Therapy

Beta-blockers should be added for symptomatic control: 2

• Use propranolol or atenolol (25-50 mg daily, titrate to heart rate <90 if blood pressure allows) 4, 2
• Beta-blockers provide relief from tachycardia and adrenergic symptoms while waiting for PTU to reduce thyroid hormone levels 2
• Continue until thyroid hormone levels normalize 2

Special Populations

Breastfeeding mothers: Both PTU and methimazole can be used safely while breastfeeding 2

Pregnant women: PTU may cause liver problems, liver failure, and death in pregnant women and may harm the unborn baby 1. However, it may be used when an antithyroid drug is needed during or just before the first trimester 1

Why PTU is Second-Line

Methimazole is superior to PTU in multiple ways: 3, 5, 6

• Greater efficacy: Methimazole 15-30 mg daily normalizes thyroid hormones more rapidly and effectively than PTU 300 mg daily 3, 5, 6
• Lower hepatotoxicity risk: PTU causes significantly more hepatotoxicity, including fulminant hepatic failure requiring liver transplant 3, 7
• Better compliance: Once-daily dosing with methimazole vs. three-times-daily with PTU 5, 6
• Faster normalization: Methimazole achieves euthyroidism in 77% of patients vs. only 19% with PTU at 12 weeks 5

Critical Pitfalls to Avoid

• Never use PTU as first-line therapy when methimazole is an option, given the substantially higher risk of fatal hepatotoxicity 1, 3
• Do not miss early signs of liver injury: Patients must be counseled to stop PTU immediately and seek care for any symptoms of hepatitis 1
• Avoid inadequate monitoring: Failure to check thyroid function every 2-4 weeks can result in over-treatment and hypothyroidism 2
• Do not overlook agranulocytosis risk: This typically occurs within the first 3 months and requires immediate discontinuation 1
• Never use radioactive iodine in breastfeeding women as an alternative, as it is absolutely contraindicated 2

Mechanism of Action

PTU inhibits thyroid hormone synthesis and also blocks peripheral conversion of T4 to T3, which may make it particularly useful in thyroid storm 1. However, it does not inactivate already-circulating thyroid hormones 1.