Antithyroid Drug-Induced Agranulocytosis: State of the Art on Diagnosis and Management

Abstract

Agranulocytosis is a rare but serious complication of antithyroid drug therapy, and an up-to-date understanding of this topic is important. Both direct toxicity and immune-mediated responses have been described as possible mechanisms. Some major susceptibility loci have recently been identified, which may lead the diagnosis of agranulocytosis into a genomic era. Onset is acute and patients present with symptoms and signs of infection together with high fever. Clinical suspicion is pivotal and should prompt blood sampling. An absolute neutrophil count of <500/μl in the presence of antithyroid drugs establishes the diagnosis. The causative drug should immediately be stopped to prevent further damage. Treatment includes broad-spectrum antibiotics and granulocyte-colony stimulation factor in selected patients. Later, patients will need definitive treatment for hyperthyroidism, usually with radioactive iodine or surgery. The best way to avoid the mortality associated with antithyroid drug-induced agranulocytosis is patient education.

Methimazole-Induced Febrile Neutropenia

“…For the treatment of ATDinduced agranulocytosis, there have been several publications which report that the use of granulocyte colony-stimulating factor (G-CSF) promptly improves the granulocyte count and suggest that it should be included in the standard treatment protocol. However, there are other publications which find G-CSF ineffective in the treatment of severe FN (2,4). In our case, G-CSF use was not employed; empirical antibiotherapy and termination of methimazole treatment were adequate in treating our patient.…”

How do paediatricians use and monitor antithyroid drugs in the UK? A clinician survey

“…Whilst 90% of respondents would stop the ATD with an ANC <0.5 × 10 9 /L, only 35% would admit to hospital. It is important to note that rates of death in children with agranulocytosis secondary to ATD have been shown to be as high as 4%, and thus, treatment with intravenous broad‐spectrum antibiotics is recommended . However, we are wary of drawing too significant a conclusion from survey data into hypothetical patient management decisions, particularly as the option to discuss blood results with an expert in the field (ie a haematologist) was not available in our multiple choice questions.…”

“…It appears that the majority of clinicians are managing hyperthyroidism without a guideline, perhaps contributing to the variation in practice demonstrated, and unable to backup verbal advice about agranulocytosis with written information. Patient education is at the heart of patient safety, and it seems timely that a national guideline and patient information leaflet to support the management of paediatric patients on ATDs is considered …”

“…patient safety, and it seems timely that a national guideline and patient information leaflet to support the management of paediatric patients on ATDs is considered. 23…”

New diagnosis of hyperthyroidism in primary care

“…Explain that there is a risk of agranulocytosis (up to 5 per 1000 patients) and hepatotoxicity (up to 1 in 250 patients with carbimazole, up to 1 in 37 patients with propylthiouracil) associated with anti-thyroid drugs 67…”