Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic symptoms: a longitudinal cohort study in the general population.

In persons with functional somatic symptoms (FSS), no conventionally defined organic pathology is apparent. It has been suggested that complex interactions of psychological, physiological, and social factors are involved in the etiology of FSS. One of the physiological mechanisms that may contribute to FSS is the function of the hypothalamic-pituitary-adrenal (HPA)-axis. This study investigates the association of HPA-axis function with cross-sectional presence and prospective development of FSS in the general population. This study was performed in a population-based cohort of 741 male and female adults (mean age 53.1, S.D. 10.9). Participants completed the somatization section of the Composite International Diagnostic Interview (CIDI) in which the presence of 43 FSS is surveyed. In addition to the total number of FSS, bodily system FSS clusters with musculoskeletal, gastrointestinal, cardiorespiratory, and general symptoms were constructed. HPA-axis function was assessed by measuring 24-h urinary free cortisol (24-h UFC) excretion. Follow-up measurements were performed approximately 2 years later. All analyses were adjusted for age, gender, body mass index, smoking, alcohol use, depression, exercise frequency, and urinary volume. Regression analysis detected no cross-sectional association between 24-h UFC excretion and the number of FSS (beta=-0.021, t=-0.521, p=0.603). In addition, 24-h UFC excretion was not associated with any of the bodily system FSS clusters (all p>0.050). Furthermore, 24-h UFC excretion did not predict new-onset FSS in the 2-year follow-up period (beta=0.021, t=0.566, p=0.572). We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population. We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population.