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Concomitant Agranulocytosis and Hepatotoxicity After Treatment with Carbimazole

Research Fellow in Endocrinology, Service of Endocrinology and Nutrition, Puerta del Mar Hospital, Cadiz, Spain

Isabel Torres, MD

Faculty Member in Endocrinology, Service of Endocrinology and Nutrition, Puerta del Mar Hospital

Amor Garcia-Valero, MD

Faculty Member in Endocrinology, Service of Endocrinology and Nutrition, Puerta del Mar Hospital

Cristina López-Tinoco, MD

Cristina López-Tinoco MD, Research Fellow in Endocrinology, Service of Endocrinology and Nutrition, Puerta del Mar Hospital

Alberto de los Santos, MD

Research Fellow in Internal Medicine, Department of Medicine, Puerta del Mar Hospital

Manuel Aguilar-Diosdado, MD

Chief of Service of Endocrinology and Nutrition, Puerta del Mar Hospital

Reprints: Dr. Aguilar-Diosdado, Service of Endocrinology and Nutrition, Puerta del Mar Hospital, Ana de Viya 21, Cadiz 11009, Spain, fax 34 956004600, manuel.aguilar.sspa{at}juntadeandalucia.es

OBJECTIVE: To describe a case of agranulocytosis and severe hepatotoxicity associated with carbimazole treatment.

CASE SUMMARY: A 37-year-old woman was diagnosed with severe hyperthyroidism resulting from Graves' disease. Treatment with carbimazole 30 mg/day was initiated. Within 15 days following the start of therapy, both minor (eg, pruritus, rash, urticaria, fever, arthralgias) and potentially life-threatening (eg, agranulocytosis, severe mixed hepatotoxicity with severe cholestatic jaundice) adverse effects developed. The patient's symptoms and laboratory abnormalities resolved following withdrawal of carbimazole. Treatment with other antithyroid drugs was not attempted, and ¹³¹I ablation of the thyroid was successfully performed. Thyroid function was maintained with standard follow-up care. Agranulocytosis, identified following bone marrow biopsy, was treated with granulocyte colony-stimulating factor.

DISCUSSION: Agranulocytosis and hepatotoxicity are rare adverse effects associated with carbimazole treatment and are usually dose- and age-related. The likelihood that carbimazole induced these undesirable events in our patient is rated as probable based on the Naranjo probability scale. We believe this case to be the first to describe minor and major adverse effects related to carbimazole therapy in a patient with Graves' disease.

CONCLUSIONS: Major adverse effects associated with carbimazole are infrequent. However, clinicians need to be aware that the effects described here, including severe liver failure and bone marrow toxicity, may occur in patients receiving this drug.

Key Words: agranulocytosis, carbimazole, hepatotoxicity

Published Online, October 31, 2006. www.theannals.com, DOI 10.1345/aph.1G720