- Autoimmune thyroiditis (AT) is more prevalent in patients with chronic idiopathic urticaria CIU) than in the general population. Previous small studies without any controlled comparison reported that CIU remits in patients with CIU and AT treated with l-thyroxine. To determine whether l-thyroxine treatment can improve the clinical course of CIU in patients with the co-occurrence of AT and CIU. A total of 749 patients with CIU were retrospectively studied. Clinical and laboratory evaluation and classification of chronic urticaria were performed according to the EAACI/GA(2)LEN/EDF/WAO guidelines. After l-thyroxine treatment for 53 ± 19 days, euthyroidism was restored in all subjects. Urticaria activity score (UAS) was evaluated at baseline and after three and six months. The control group consisted of matched 44 euthyroid subjects with CIU. A total of 44 (5.9%) patients were diagnosed to have hypothyroidism related to AT. Autologous serum skin test (ASST) was found to be positive in 17 (38.6%) of them. There was no statistically significant difference in baseline UAS, between the ASST+ (3.94 ± 1.52) and the ASST− (3.63 ± 1.42; P = 0.27) hypothyroid subjects and the euthyroid CIU controls (3.73 ± 1.74). During the l-thyroxine treatment, a significant reduction of UAS was observed in both hypothyroid ASST+ and ASST− subjects. However, the mean UAS after three and six months of l-thyroxine treatment remained not significantly different from that in control euthyroid subjects with CIU. l-Thyroxine treatment has no effect on the course of CIU in patients with CIU and AT.