What is the recommended propylthiouracil (PTU) dosing regimen for an adult with thyrotoxicosis, including initial dose, maximum dose, thyroid storm dosing, maintenance dose, and considerations for first‑trimester pregnancy?

PTU Dosing in Thyrotoxicosis

Initial Dosing for Adults

For adults with thyrotoxicosis, start propylthiouracil (PTU) at 300 mg daily divided into three equal doses given every 8 hours. 1

• In patients with severe hyperthyroidism or very large goiters, the initial dose may be increased to 400 mg daily 1
• Occasionally, patients may require 600–900 mg daily initially for adequate control 1
• The total daily dose should be divided into three equal portions administered at approximately 8-hour intervals to maintain consistent drug levels 1

Maintenance Dosing

Once thyroid function is controlled, reduce PTU to a maintenance dose of 100–150 mg daily. 1

• Continue monitoring thyroid function tests periodically during therapy 1
• An elevated serum TSH once clinical hyperthyroidism has resolved indicates the need for a lower maintenance dose 1

Thyroid Storm Dosing

In thyroid storm during pregnancy, initiate PTU immediately as part of a multi-drug emergency regimen without waiting for laboratory confirmation. 2, 3

• Combine PTU with potassium or sodium iodide solutions (given at least 1 hour after PTU), dexamethasone 2 mg IV every 6 hours, propranolol 60–80 mg orally every 4–6 hours, and supportive care 2
• Never administer iodine before the thionamide, as this provides substrate for new hormone synthesis and can worsen thyrotoxicosis 2
• Thyroid storm requires immediate treatment; delivery should be avoided during active storm unless absolutely necessary 2, 3

First-Trimester Pregnancy Dosing

PTU is the preferred antithyroid drug exclusively during the first trimester of pregnancy to minimize congenital malformations. 3

• Start with standard adult dosing (300 mg daily in divided doses) and adjust to maintain free T4 in the high-normal range using the lowest effective dose 3
• Check free T4 or free thyroxine index (FTI) every 2–4 weeks to guide dose adjustments 3
• Switch to methimazole after the first trimester (beginning in the second trimester) to reduce maternal hepatotoxicity risk while continuing to minimize fetal exposure 3, 4
• The goal is to maintain mild maternal hyperthyroidism rather than complete euthyroidism to avoid fetal thyroid suppression 3

Pediatric Dosing (Rarely Indicated)

PTU is generally NOT recommended in pediatric patients except in rare instances when methimazole is not tolerated and surgery or radioactive iodine are inappropriate. 1

• If absolutely necessary in patients ≥6 years old, initiate at 50 mg daily with careful upward titration based on clinical response and TSH/free T4 levels 1
• Severe hepatic failure including liver transplantation and death have been reported in children, making methimazole the preferred agent in this population 1, 5, 6
• Most cases of severe liver injury in children occurred with doses ≥300 mg/day, though cases have been reported with doses as low as 50 mg/day 1, 5

Geriatric Dosing

In elderly patients, use cautious dose selection reflecting the greater frequency of decreased hepatic, renal, or cardiac function. 1

• Start at the lower end of the dosing range (300 mg daily) 1
• Monitor more closely for adverse effects given potential comorbidities and concomitant medications 1

Critical Safety Monitoring

Patients must report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise, as these may signal agranulocytosis. 1

• Obtain an immediate complete blood count if sore throat or fever develops, and discontinue PTU if agranulocytosis is confirmed 3, 1
• Monitor for hepatic dysfunction symptoms (anorexia, pruritus, right upper quadrant pain, jaundice, dark urine) and discontinue PTU immediately if these occur 1, 5
• Consider monitoring prothrombin time during therapy, especially before surgical procedures, as PTU may cause hypoprothrombinemia 1
• Watch for vasculitis symptoms (new rash, hematuria, decreased urine output, dyspnea, hemoptysis) and discontinue PTU promptly if suspected 1

Important Clinical Pitfalls

Failing to switch from PTU to methimazole after the first trimester increases the risk of maternal hepatotoxicity. 3

• PTU-induced severe liver injury can occur after relatively short treatment periods (≥4 months in 75% of pediatric cases and 64% of adult cases) 7
• Radioactive iodine (I-131) is absolutely contraindicated during pregnancy as it causes fetal thyroid ablation 2, 3
• Both PTU and methimazole are compatible with breastfeeding, as only minimal amounts enter breast milk 3, 1
• Untreated or inadequately treated hyperthyroidism increases risks of severe preeclampsia, preterm delivery, heart failure, miscarriage, and low birth weight 3