Endocrine Abstracts

Introduction: Antithyroid drugs (ATDs) are generally safe and well tolerated, however, major side effects such as hepatotoxicity and agranulocytosis may occur and patients should be provided information on the major symptoms of these conditions. Although rare, agranulocytosis appears to be more likely with propylthiouracil (PTU) at any dose than with low-dose Methimazole (MMI).

Clinical Case: We describe the case of a 70-year-old woman referred to Endocrinology for persistent Subclinical Hyperthyroidism (SH). Her previous medical history was relevant for dyslipidemia, treated with simvastatin 40 mg, once daily. Sixteen years before, she was evaluated for diplopia and fatigue due to an unknown thyroid dysfunction and was managed with PTU, suspended due an alteration in the white blood cells. There were no other known medical conditions or allergies. On presentation to our clinic, in August 2021, she reported worsening of anxiety with no other symptoms. On examination her thyroid was not enlarged, and no signs of Graves’ ophthalmopathy or fine tremors were present. A thyroid ultrasound revealed an enlarged thyroid with a 5mm cystic node. Thyroid function tests revealed low thyroid-stimulating hormone (TSH) 0.252 μUI/ml and normal free thyroxine (fT4) 1.12 ng/dl. MMI 2.5 mg daily was started for symptomatic control. After 2 months, the analytical study showed a maintenance of SH and a decrease in the white blood cell count from 3.92x10^9/l to 2.28x10^9/l. Methimazole was suspended while awaiting anti-thyroid stimulating hormone receptor antibodies (TRAbs) and thyroid scintigraphy. Six days later, the patient presented to the emergency room with a 2-day history of pharyngitis, fever, headache, nausea and vomiting. Blood tests revealed worsened leukopenia 160x10^9/l with severe neutropenia with 0 cells. Broad spectrum antibiotherapy was started. Polyclonal pANCA:AntiMPO antibodies were detected and bone marrow examination revealed severe hypocellularity with rare neutrophils. Granulocyte-colony stimulating factor was administered for 6 days. The patient was discharged after 12 days with a normal leukocyte and neutrophil count, with the diagnosis of methimazole induced agranulocytosis.

Conclusion: A rare life-threatening side-effect of ATDs is agranulocytosis. Patients with fever or pharyngitis should seek immediate medical help. If granulocytopenia is confirmed, ATD should be suspended. Switching to the other ATD is contraindicated, because a cross-reaction between PTU and MMI has been observed. The onset of agranulocytosis is sudden and patients should be educated for warning signs at time of prescription.