Associations Between Fatigue and Endocrine and Non-endocrine Health Problems in Turner Syndrome: Cohort Study and Review

CONTEXT:Turner syndrome (TS) is a rare chromosomal disorder characterized by gonadal dysfunction, short stature, and heart defects, among other features. Women with TS often suffer from severe fatigue, for which they are typically referred to endocrinologists. The diagnostic work-up is generally time-consuming and invasive, and it rarely solves the problem. To prevent the personal and financial burden of unnecessary diagnostic procedures, it is crucial to understand fatigue in TS.OBJECTIVE:To explore the association between fatigue and endocrine and non-endocrine comorbidities in a-for rare disorders-large group of women with TS.METHODS:170 genetically confirmed women with TS who attended the TS Reference Center underwent a systematic health screening, including a structured interview, complete physical examination, biochemical measurements, perceived stress and fatigue questionnaires, and additional tests when indicated.RESULTS:Median (interquartile range) age was 32.6 (23.9-41.4) years. Severe fatigue was experienced by 1 in 3 women with TS. Liver enzyme disturbances and body mass index were significantly associated with higher fatigue scores. Perceived stress was highly correlated with fatigue.CONCLUSION:There was no association between fatigue and most endocrine and non-endocrine disorders, which implies that fatigue is only partly explained by somatic disorders. The high correlation between perceived stress and fatigue suggests that TS-related neuropsychological processes may play an important role in the etiology of fatigue in women with TS. We provide a practical algorithm for the endocrine, non-endocrine, and psychological approach to fatigue in women with TS.