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Mov Disord. 2010 Jun 15;25(8):1047-52. doi: 10.1002/mds.23026.

Restless legs syndrome: evidence for nocturnal hypothalamic-pituitary-adrenal system activation.

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  • 1Sleep Laboratory, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.


Epidemiological studies consistently point to a relationship between restless legs syndrome (RLS) and cardiovascular disease. The mechanism underlying this association is unclear. Activation of the hypothalamic-pituitary-adrenal (HPA) system has been shown to contribute to the metabolic syndrome and an enhanced cardiovascular risk. We investigated cortisol levels as an indicator of HPA system activity in RLS during the nighttime, when RLS symptoms are at their maximum. We assessed nocturnal urinary cortisol excretion in 73 patients with RLS and 34 healthy controls, controlling for age and gender. Urine sampling was paralleled by polysomnographic recordings. We found significantly enhanced nocturnal cortisol excretion in RLS, demonstrating nocturnal HPA system overactivity in RLS. HPA system overactivity is a possible mechanism contributing to the enhanced load of cardiovascular disease in RLS patients. Nocturnal cortisol release showed weak correlations with some polysomnographic parameters of disturbed sleep, making a potential contribution of RLS-induced sleep disruption to HPA system activation conceivable.

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