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Increased 24-hour urinary cortisol and decreased endocrine and sleep response to metyrapone in posttraumatic stress disorder
We examined 24 male subjects with combat-related PTSD and 18 male combat-exposed normal controls. 24-hour urinary free cortisol and three nights of polysomnography were obtained. On day 3 metyrapone was administered during normal waking hours until sleep onset. Endocrine responses to metyrapone were measured the morning following sleep recordings before and after administration. PTSD patients showed higher 24-hour urinary cortisol concentrations compared to controls and had significantly less delta sleep at baseline. PTSD subjects had a significantly decreased ACTH response to metyrapone compared to controls. Metyrapone caused a marked decrease in delta sleep that was significantly greater in controls compared to PTSD. The decline in delta sleep was significantly correlated with the increase in ACTH. The results suggest that the delta sleep response to metyrapone is a measure of the brain response to increases in hypothalamic CRF. Increased 24-hour urinary cortisol concentrations and the diminished ACTH and delta sleep response in PTSD could be explained by increased CRF drive in patients at baseline.
Part of this work was supported by the Deutsche Forschungsgemeinschaft (Ot 209/2–1) and by the National Institute of Health (Neylan: MH057157).
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