To the Editor:
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing vasculitis in small-sized vessels such as arterioles, capillaries, and venules1. The possibility of a link between thyroid dysfunction and autoimmunity has been considered and its prevalence was reported differently according to each autoimmune disease2. Given that AAV is one of the systemic autoimmune diseases affecting most major organs3, and there is cross-reactivity between thyroid peroxidase and myeloperoxidase (MPO) molecules4, the prevalence of thyroid dysfunction, including autoimmune thyroiditis, may be increased in patients with AAV. Previous studies reported the higher prevalence of thyroid dysfunction in patients with AAV than in the general population5,6,7. However, there was no study on the prevalence of thyroid dysfunction in AAV patients in Korea. In this study, we investigate the prevalence of thyroid dysfunction and searched for the predictors at diagnosis of its development during followup for 3 months or greater in Korean patients with AAV.
We retrospectively reviewed the medical records of 186 patients with AAV, who were classified as having AAV at the Department of Rheumatology, Yonsei University College of Medicine, Severance Hospital, from October 2000 to July 2018. They met the 2007 European Medicines Agency algorithms and the 2012 Chapel Hill Consensus Conferences Nomenclature of Vasculitis1,8. All patients had well-documented medical records regarding both AAV and thyroid diseases. This study was approved by the Institutional Review Board (IRB) of Severance Hospital (4-2017-0673), and patient written informed consent was waived by the approving IRB, because this was a retrospective study.
The followup duration was defined for patients with thyroid dysfunction as the period from diagnosis to development, and as the period from diagnosis to the last visit for those without thyroid dysfunction. Overt thyroid dysfunction was approved by the International Classification Diseases, 10th revision, or by medications searched through the Korean Drug Utilisation Review system. Subclinical hyperthyroidism was defined when a thyroid-stimulating hormone (TSH) level is suppressed, but a triiodothyronine (T3) level is within a normal range, whereas subclinical hypothyroidism was defined when a TSH level is enhanced but a free thyroxine (T4) level is within a normal range9. Differences in variables between the 2 groups were analyzed using the chi-square and Fisher’s exact tests or the Mann-Whitney U test. Comparison of cumulative thyroid dysfunction–free survival between the 2 groups was analyzed by the Kaplan-Meier survival analysis. P values < 0.05 were considered statistically significant.
Twenty-seven of 186 patients (14.5%) exhibited thyroid dysfunction, and 7 of them had overt thyroid dysfunction before diagnosis of AAV (Supplementary Table 1, available from the authors on request). The overall prevalence was lower than in previous studies (20.0–21.5%), but similar to that of another previous study (14.5%)5,6,7. Based on the report on thyroid dysfunction in the Korean general population10, patients with AAV exhibited the significantly increased prevalences of overt hyperthyroidism and hypothyroidism compared to the general population (5.4% vs 0.5% and 4.3% vs 0.7%, respectively). Also, patients with AAV exhibited a lower prevalence of subclinical hyperthyroidism than the general population (1.6% vs 3.0%) but not subclinical hypothyroidism (3.2% vs 3.1%).
When we divided 186 AAV patients into the 2 groups according to the presence of thyroid dysfunction, we found that patients with thyroid dysfunction had MPO-ANCA [or perinuclear (P)-ANCA] at diagnosis more frequently than those without (81.5% vs 61.0%). During followup, chronic kidney disease (stages 3–5) and ischemic heart disease were observed in patients with thyroid dysfunction more commonly than in those without, which could suggest that thyroid dysfunction might influence the development of chronic kidney disease or ischemic heart disease. Immunosuppressive drugs were evenly administered to both groups (Table 1).
In the analysis of the development of thyroid dysfunction after AAV diagnosis, we divided 179 AAV patients into 2 groups according to each variable at diagnosis and searched for the predictors. Patients with MPO-ANCA (or P-ANCA) and the 2009 5-factor score ≥ 2 at diagnosis exhibited the lower cumulative thyroid dysfunction–free survival than those without during followup (Figure 1). Age ≥ 65 years, ANCA positivity, and renal involvement at diagnosis, but not sex, were also predictors of thyroid dysfunction (Supplementary Figure 1, available from the authors on request). It was reported that propylthiouracil (PTU) could induce AAV development, particularly in women with renal involvement6. In this study, because only 1 patient received PTU 8 months before AAV diagnosis, we could not clarify it.
Our study has several limitations of retrospective and monocentric study designs. The number of patients was not large enough to represent all Korean patients with AAV and no requalified results were available in all patients. However, this study is a pilot study to first discover the prevalence and the predictors at diagnosis of thyroid dysfunction in Korean patients with AAV. In the future, prospective studies with a larger number of patients and the serial results of thyroid function test will provide more reliable and validated information on the clinical implication of thyroid dysfunction in patients with AAV.
Footnotes
This study was supported by a faculty research grant of Yonsei University College of Medicine (6-2016-0145) and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI14C1324).