Thyroid hormones and complement parameters in hereditary angioedema with C1-inhibitor deficiency

Abstract Background Thyroid hormones control and up-regulate the synthesis of many plasma proteins. Objective To explore possible associations between thyroid hormone and complement levels in patients with hereditary angioedema resulting from the deficiency of the C1-inhibitor (C1-INH-HAE). Methods In this case-control study, serum thyrotropin, free triiodothyronine (FT 3 ), and free thyroxine (FT 4 ) levels, anti–thyroid peroxidase and antithyroglobulin antibody titers, and C1-INH concentrations were measured in 117 euthyroid patients with C1-INH-HAE and compared with their clinical properties. The control group comprised 150 healthy, age- and sex-matched, euthyroid individuals. Results The thyrotropin and antithyroglobulin levels were similar between the patients and the controls. Significantly lower FT 3 ( P 4 ( P  = .002) levels, as well as higher anti–thyroid peroxidase titers ( P 4 levels than among those with above-median values ( P  = .02). Patients who experienced more edematous attacks per year had lower FT 4 levels (within the normal range) than those afflicted by fewer episodes ( P  = .01). The FT 3 and FT 4 levels were significantly higher in patients undergoing long-term danazol therapy than in those who did not receive this drug ( P  = .01 and P  = .02, respectively). The proportion of patients with FT 4 levels in the below-median range was higher in the subset with increased d-dimer concentration ( P  = .009). Conclusion Minor variations of the thyroid hormone levels (within the reference range) can influence the function of C1-INH in C1-INH-HAE. Our findings suggest a role for the endocrine system in the pathophysiology of C1-INH-HAE.