From the Guidelines
Yes, it is contraindicated to trial propylthiouracil (PTU) in a patient with a history of carbimazole-induced agranulocytosis. These medications share a cross-reactivity risk because both PTU and carbimazole (as well as its active metabolite methimazole) are thionamide antithyroid drugs with similar mechanisms of action. A patient who has experienced agranulocytosis with one thionamide has approximately a 50% chance of developing the same reaction with the other, as suggested by the potential for similar side effects such as agranulocytosis, hepatitis, vasculitis, and thrombocytopenia 1. Agranulocytosis is a potentially life-threatening condition characterized by severely decreased neutrophil counts, leaving patients vulnerable to serious infections. For patients with carbimazole-induced agranulocytosis, alternative treatment options for hyperthyroidism should be pursued instead, such as radioactive iodine therapy or thyroidectomy. In emergency situations where rapid control of thyrotoxicosis is needed before definitive treatment, non-thionamide options like beta-blockers, corticosteroids, cholestyramine, and iodine solutions may be used temporarily. The contraindication exists because the risk of recurrent agranulocytosis outweighs any potential benefit of switching between thionamide medications.
Key considerations in managing such patients include:
- Monitoring for signs of agranulocytosis, such as sore throat and fever, and promptly discontinuing the thioamide if these symptoms develop 1.
- Using the lowest possible thioamide dosage to maintain FT4 or FTI in the high-normal range, if a thioamide must be used.
- Exploring alternative treatments that do not carry the risk of cross-reactivity and agranulocytosis.
- Considering the potential for other side effects such as hepatitis, vasculitis, and thrombocytopenia when selecting a treatment option 1.
Given the potential risks, alternative treatments should be prioritized over PTU in patients with a history of carbimazole-induced agranulocytosis, focusing on minimizing morbidity, mortality, and improving quality of life.
From the Research
Propylthiouracil (PTU) Contraindication in Patients with Carbimazole-Induced Agranulocytosis
- The use of PTU in patients with a history of carbimazole-induced agranulocytosis is a concern due to the potential for cross-reactivity between the two medications 2.
- A study reported two cases of carbimazole-induced agranulocytosis, and both patients were treated with radioiodine after resolution of the agranulocytosis, as it is possible for patients to develop agranulocytosis with PTU as well 2.
- Another study suggested that treatment with PTU is also contraindicated in patients with methimazole-induced agranulocytosis, implying a potential cross-reactivity between the medications 3.
- However, a retrospective study of 603 patients with Graves' disease found no cases of agranulocytosis due to PTU, although the study did report cases of agranulocytosis due to methimazole and carbimazole 4.
- The risk of cross-reactivity between antithyroid drugs, including PTU and carbimazole, highlights the need for careful monitoring and consideration of alternative treatments in patients with a history of agranulocytosis 5.
Alternative Treatments for Hyperthyroidism
- In patients with a history of carbimazole-induced agranulocytosis, alternative treatments for hyperthyroidism may be necessary, such as radioiodine or surgical interventions 2.
- A case report described the use of saturated solution of potassium iodide (SSKI) as a bridge therapy to manage thyrotoxicosis in a patient with methimazole-induced agranulocytosis 3.
- Other alternative treatments, such as beta-blockade, cholestyramine, and plasmapheresis, may also be considered in patients with a history of agranulocytosis 3.