Treatment with Propylthiouracil is Associated with Appearance of Antineutrophil Cytoplasmic Antibodies in Some Patients with Graves' Disease

Abstract

The use of propylthiouracil (PTU) for the treatment of Graves' disease is associated with few adverse effects such as skin eruptions, liver dysfunction, and agranulocytosis. Furthermore, recent studies described the development of antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis and vasculitis in patients treated with PTU. Here we investigated whether PTU therapy per se is associated with the appearance of ANCA in patients with Graves' disease. We analyzed 119 serum samples from 117 patients with Graves' disease treated with either PTU (n = 56), or methimazole (MMI) (n = 21), as well as untreated patients (n = 42). Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA were tested by enzyme-linked immunosorbent assay (ELISA) kits. MPO-ANCA was negative in all patients treated with MMI therapy and untreated patients. However, MPO-ANCA was detected in 21 (37.5%) of 56 patients treated with PTU therapy. Furthermore, two patients who were negative for MPO-ANCA became positive after PTU therapy. The proportion of patients positive for MPO-ANCA increased with the prolongation of PTU therapy, but did not correlate with age, gender, and positive antithyroperoxidase (TPO) antibody. Among 21 MPO-ANCA positive patients, 12 had no symptoms, but 9 patients complained of myalgia, arthralgia, or common cold like symptoms after the appearance of MPO-ANCA. Three patients developed agranulocytosis or granulocytopenia, but none showed abnormal urinary findings. Our results suggest that PTU per se is associated with the production of MPO-ANCA in patients with Graves' disease.

Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs: A long‐term followup study

“…Although ANCA are present relatively often in patients treated with antithyroid drugs, the prevalence of AAV is much lower (22,(27)(28)(29). In our study, 7 of 11 patients treated with antithyroid drugs who were positive for MPO, PR3, or HLE ANCA did not have, or develop, vasculitis (64%).…”

“…Clinical signs were present in 2 of 6 ANCA-positive 110 Slot et al patients who had used PTU, in 2 patients using other antithyroid drugs, and in none of the patients who were not treated with antithyroid drugs. The presence of ANCA, and of ANCA-associated vasculitis, in patients using antithyroid drugs for treatment of hyperthyroidism have been recurrently reported (15)(16)(17)(18)(19)(20)(21)(22)(23)27). Reported prevalence of ANCA in patients treated with antithyroid drugs varies from 4% to 46%; prevalence of AAV is lower (0 -1.4%) (22,(27)(28)(29).…”

Auto-imunidade ANCA (Anticorpo Anti-Citoplasma de Neutrófilos) positiva induzida por propiltiouracil: relato de caso e revisão da literatura

“…A prevalência de ANCA-MPO nos usuários de drogas antitireoidianas varia de 25-60% nos pacientes tratados com PTU, e de 3,4% nos tratados com metimazol (29)(30)(31). Em uma análise, Sato e cols.…”

“…O ANCA-p teve uma correlação significativa com o anticorpo antitireoglobulina e não houve correlação com o anticorpo anti-tireoperoxidase, sugerindo que a severidade da Doença de Graves pode ser um fator responsável para positividade do ANCA-p (1). A proporção de pacientes positivos para este anticorpo aumenta com a duração da terapia, porém não há correlação com idade ou sexo (29). Da mesma forma, não foi relatado aumento da prevalência do ANCA em pacientes com tireoidite de Hashimoto (30).…”

Cytoplasmic Pattern Anti-neutrophil Cytoplasmic Antibody (cANCA)-positive Cutaneous Leukocytoclastic Vasculitis Induced by Propylthiouracil: A Case Report

“…Despite all medical therapeutic interventions, the patient could not be saved and died due to nosocomial pneumonia and septic shock. www.medicinescience.org | Med-Science 651 more than 18 months has been reported to be associated with the development of ANCA [12,15,16]. Some studies have even reported an increase in ANCA positivity with longer duration of PTU use [17].…”