Propylthiouracil (PTU)-Induced Agranulocytosis Treated with Recombinant Human Granulocyte Colony-Stimulating Factor (G-CSF)

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Abstract
Two premenopausal female patients with Graves' hyperthyroidism and propylthiouracil (PTU)-induced agranulocytosis are presented. The first patient, age 47, received 300 mg of PTU per day and developed agranulocytosis within 6 weeks of the commencement of therapy. There were no granulocytes in the peripheral smear and a bone marrow biopsy demonstrated an absence of the entire myeloid cell line as well as the presence of many granulomas. The second patient, age 39, received PTU 1600 mg per day for two and half weeks and then 2 days of methimazole, 200 mg per day. She developed complete agranulocytosis on peripheral smear within 3 weeks of the initiation of therapy. Her bone marrow biopsy demonstrated maturation arrest of the granulocytic cell line at the myelocyte stage. In addition to discontinuing their antithyroid drugs, both patients were treated with G-CSF subcutaneously. The first patient received 300 μg of G-CSF on days 2 and 4 after discontinuing PTU with the appearance of 4.7 × 109/L granulocytes and granulocyte precursors on day 4. The second patient received 575 μg of G-CSF for 2 days and 300 μg for 1 additional day beginning on the third day after discontinuing antithyroid drugs. On the second treatment day there were 5.8 × 109/L granulocytes and granulocyte precursors on the peripheral smear. A comparison to previously published cases on antithyroid drug induced agranulocytosis suggests that the use of G-CSF decreased the amount of time required for marrow recovery after the cessation of the offending drug.