Endocrine Abstracts

Case: A 43 years old female with a PMHx of Graves disease initially treated with methimazole (discontinued due to arthralgias) and started on propylthiouracil (PTU). Three years ago she went into remission and the PTU was stopped. About 6 weeks ago, the patient started experiencing typical symptoms of hyperthyroidism including palpitations and hot sweats so she was restarted her on PTU. Patient started noticing fever, chills, myalgias and dry cough. In the hospital her Temperature was 102.4 F, pulse was 137 beats/min with sinus tachycardia. Labs showed Wbc – 1.2 K/cm with neutrophils of 7%, TSH – 0.2 μlU/ml, T₄ – 3.2 ng/dl and T₃ uptake – 42%. Peripheral smear showed decreased white blood cell count with otherwise mature lymphocytes and RBC. Physical examination showed hyperreflexia of the extremities with tremors. She was started on antibiotics for neutropenic fever and propranalol for the sinus tachycardia. An extensive work up for neutropenia was negative including vitamin B12, folic acid, serology for viral infections (hepatitis, HIV, CMV, EBV, parvovirus), lupus antigen and pan-cultures. Bone marrow aspirate revealed maturation arrest in granulocytic lineages at the myelocyte/metamyelocyte stage. Flow cytometry showed 4% myeloblasts and very few normal maturing myeloid cells. PTU was thought to be the culprit as a diagnosis of exclusion. Patient was given granulocyte stimulating factor and this improved her WBC count.

Discussion: Agranulocytosis is a rare but serious complication of thionamide therapy, with a prevalence of 0.1–0.5%. It can occur as early as 10 days after starting therapy or may be delayed for up to 3 months. The immune reactions occur via IgE-mediated hypersensitivity, drug-induced IgG/IgM response and neutrophil–drug complexes. Antigranulocyte antibodies have been reported in some patients which could explain the reaction for the second time initiation of the medication.