Carbimazole-induced agranulocytosis in two sisters

Summary

Case 1. A 29-year old female presented in 1970 with a history of a lump in the throat, tiredness, weight loss, increased appetite, feeling hot, sweatiness and irritable mood swings. On examination, she had hot sweaty hands, tremor, tachycardia and a diffusely enlarged thyroid gland. An I¹³¹ uptake of 68% at 3 hours and a protein-bound iodine of 1386 nmol/1 (normal 300 to 600 nmol/1) confirmed the clinical diagnosis of thyrotoxicosis. Treatment with carbimazole (20 mg t.d.s.) was instituted. After 1 week she began to develop myalgia, malaise and fever. Seventeen days after starting treatment she developed a sore mouth, sore gums and injection of the fauces. She was admitted to hospital where a total white count of 1100/mm³ was found, with 22% lymphocytes, 78% monocytes and a total absence of neutrophils. Haemoglobin and platelets were within normal limits. Bone marrow showed a maturation arrest with no myeloid neutrophils beyond the myelocyte stage. A diagnosis of carbimazole-induced agranulocytosis was made and the drug withdrawn. She was treated with antibiotics, nystatin suspension, steroids and an infusion of unirradiated chronic myeloid cells using the I.B.M. cell separator. There was a rapid improvement in the clinical and haematological condition and within 2 weeks her neutrophils numbered 60% of 15, 700/mm³. These white cells did not have the Philadelphia chromosome and were therefore being manufactured by the patient. Her thyrotoxicosis was subsequently controlled with potassium perchlorate without complications, followed by partial thyroidectomy.