Stress Triggers the Onset and the Recurrences of Hyperthyroidism in Patients with Graves' Disease

The aim of this study was to evaluate the relationship of stressful events (SE) with the onset and outcome of Graves' disease (GD). Over a period of 21 years, we enrolled 58 consecutive patients in whom at least one SE had occurred ≤12 months before the onset of GD. Patients were treated with antithyroid drugs (ATD) for ≥12 months and followed up for ≥5 years after ATD withdrawal. We divided patients in three groups: REM (who reached remission; 25.9%); EXA (who experienced ≥1 exacerbation during ATD; 10.3%); and REL (who experienced ≥1 relapse after ATD withdrawal; 63.8%). The average age at onset was similar in the three groups. All males aged ≤25 years at GD onset relapsed at least once; no patient aged ≥51 years at GD onset relapsed ≥2 times. All patients who exacerbated or relapsed had at least one SE preceding each exacerbation or relapse. The time lag between SE and onset of GD (19.3±11.9 weeks) correlated with the age at onset (r=0.292, P=0.0002), particularly in the REL group (r=0.346, P=0.001). Overall, EXA and REL patients experienced more SE than REM patients (P=0.0002 and P=0.003, respectively). In the REL group, the overall number of SE was correlated with the number of relapses (r=0.486, P<0.0001). There exist GD patients who are prone to develop hyperthyroidism and its recurrences when exposed to SE. They are relatively young; the younger these patients are, the shorter is the time lag between SE and the onset of hyperthyroidism.