Death by Suicide in Graves' Disease and Graves' Orbitopathy: A Nationwide Danish Register Study

BACKGROUND: Graves' disease (GD) is associated with excess morbidity and mortality, but little is known about unnatural manners of death and the potential relation with Graves' orbitopathy (GO). This study investigated the risk of unnatural death in Graves' patients with and without orbitopathy compared to matched control populations. METHODS: This was a cohort study covering all adult Danes (≥18 years) diagnosed with GD or GO during 1995-2012. Median follow-up time was 7.9 years (range 0-17.5 years). Utilizing the Danish Register of Causes of Death and the Danish National Patient Registry, 28,461 subjects with GD and 3965 with GO were identified and matched for age and sex with four subjects from the background population. The manner of death was identified, and hazard ratios (HR) for mortality due to unnatural deaths (accident, suicide, violence/homicide, and unknown) were calculated using Cox regression analyses, adjusted for pre-existing somatic and psychiatric morbidity. RESULTS: In Graves' disease overall (GD + GO), there was an increased risk of death from unknown unnatural manners (HR = 2.01 confidence interval (CI) 1.17-3.45, p = 0.012) and of suicide, although the latter difference was not with certainty statistically significant (HR = 1.43 CI 1.00-2.04, p = 0.053). There was no significant difference in risk of death from suicide in GD subjects compared to their controls (HR = 1.27 CI 0.85-1.89, p = 0.253). However, GO patients had a significantly higher risk of death from suicide (HR = 2.71 CI 1.16-6.32, p = 0.022). CONCLUSIONS: Mortality by suicide was increased in Graves' disease overall, most significantly in patients with GO, also after adjustment for pre-existing somatic and psychiatric disease. These findings indicate that GD and GO may have a significant role in the pathophysiological mechanisms of suicidal behavior. Beyond independent confirmation, reasons for this need to be explored in order to introduce preventive measures.