Timing of antithyroid drug-induced MPO-ANCA vasculitis increased with propylthiouracil

Issue: October 2009

New data suggest that the timing of antithyroid treatment-induced myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis is rare, unpredictable and is increased with propylthiouracil.

Researchers in Japan assessed the incidence of MPO-ANCA-associated vasculitis as an adverse reaction to antithyroid treatment in 92 patients with Graves’ disease. They determined the time of onset, drug and dose taken and overall relationship with clinical symptoms and MPO-ANCA-associated vasculitis titer and incidence.

The median time of onset of MPO-ANCA-associated vasculitis was 42 months after initiation of treatment. The median dose at onset was 15 mg methimazole and 200 mg propylthiouracil daily; 25% of patients took methimazole from 1979 to 2007 and 75% took propylthiouracil from 1982 to 2007.

Complication symptoms ranged from minimal to severe: 45% of patients had single-organ failure, 35% had two organ failure (commonly kidneys and respiratory organs), 14% had three-organ failure (commonly kidneys, joints and skin), 2% had four-organ failure and 4% had unknown organ failure. The majority of patients with the condition had severe symptoms (86%).

Sixty-seven percent of patients experienced resolution of MPO-ANCA-associated vasculitis, 23% had persistent sequelae and 2% died.

The median MPO-ANCA titer was 230.5 Elisa units for 83% of patients. The researchers reported titers of 317 Elisa units and 489 Elisa units in the two patients who died. Titers did not statistically differ among patients with different degrees of symptom severity or multiple organ involvement. After antithyroid medication was discontinued, the MPO-ANCA titer decreased in 40 of 50 patients.

The researchers’ estimates indicate that MPO-ANCA-associated vasculitis is present in between 0.53 patients per 10,000 and 0.79 per 10,000 patients in Japan. Further, the estimated incidence of the condition for propylthiouracil is 39-fold that for methimazole.

“It is impossible to predict when MPO-ANCA-associated vasculitis will occur,” the researchers wrote. “Moreover, the dependence of antithyroid drug dose on MPO-ANCA-associated vasculitis is uncertain.”

In an accompanying editorial, Ernest L. Mazzaferri, MD, acknowledged that the study was small and lacked data on the relationship between antithyroid drug dose and duration and the exclusivity associated with propylthiouracil and MPO-ANCA-associated vasculitis.

“The authors recommend that propylthiouracil should be discontinued immediately after the diagnosis of MPO-ANCA-associated vasculitis and that immunosuppressive therapy should be used only in patients with vital organ involvements and that long-term maintenance therapy may not be necessary,” Mazzaferri wrote in the August issue of Clinical Thyroidology. – by Jennifer Southall

Noh JY. J Clin Endocrinol Metab. 2009;94:2806-2811.

This large series of patients with antithyroid drug-induced MPO-ANCA vasculitis should alert physicians to this rare but important complication of treatment with propylthiouracil and methimazole. The clinical manifestations vary depending on which organ is involved and can occur at any time during the course of therapy. Neither the presence of MPO-ANCA nor the MPO-ANCA titer is necessarily associated with the vasculitis, so there is not specific testing that can be done to predict this reaction. The majority of reported cases were with propylthiouracil, but methimazole is used almost fivefold more than propylthiouracil in Japan. The researchers concluded that MPO-ANCA vasculitis is much more common with propylthiouracil than methimazole. With the recognition of more severe liver toxicity with propylthiouracil compared with methimazole, this report should further encourage the use of methimazole over propylthiouracil.

– Gregory A. Brent

Endocrine Today Editorial Board member