Thyroid-Stimulating Hormone Receptor Autoimmunity and Local Factors in Multiple Risk Factors Are Mainly Involved in the Occurrence of Pretibial Myxedema

BACKGROUND: Pretibial myxedema (PTM) is a local mucinous dermopathy associated with thyroid diseases. Since the etiology of PTM is unclear, the aim of this study is to identify the risk factors for PTM and their etiological roles in PTM occurrence. METHODS: A large-scale case-control study (n = 1,200) was performed to identify risk factors for PTM by calculating odds ratio (OR) values and 95% confidential intervals. The PTM group entered a glucocorticoid treatment trial. Patients with complete response were followed up to the first relapse in a cohort study. The relative risk (RR) values of the main risk factors were calculated for PTM relapse to test their etiological roles. RESULTS: Among the 19 factors, six risk factors were identified: thyroid-stimulating hormone (TSH) receptor antibody (TRAb) (OR 42.93), autoimmune thyroid disease (AITD) or AITD history (OR 10.30), local trauma (OR 6.55), venous stasis posture (OR 6.16), cigarette smoking (OR 4.48), and age (OR 1.05). Serum TRAb levels were positively correlated with the severity of PTM. Of note, 371/400 patients received glucocorticoid treatment, and 330 achieved complete response. The serum TRAb levels after treatment decreased dramatically compared with those before treatment. After stopping glucocorticoid treatment, serum TRAb levels increased significantly when PTM relapsed (P < 0.001). In 165 relapse cases, an increase in serum TRAb levels occurred first, followed by persistent venous stasis posture or local trauma and finally PTM. The RR of elevated serum TRAb levels was 6.73 in PTM relapse cases. In the elevated serum TRAb level group, the RRs of local trauma, venous stasis posture, and local trauma plus venous stasis posture were 8.81, 6.5, and 8.84, respectively, for PTM relapse cases. CONCLUSIONS: TSHR autoimmunity and local factors in the six identified risk factors are the main causes of PTM occurrence.