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Decreased Delta-Sleep and Plasma Delta-Sleep-Inducing Peptide in Patients with Cushing SyndromeFriedman T.C.a,b · García-Borreguero D.c · Hardwick D.b · Akuete C.N.b · Doppman J.L.e · Dorn L.D.b,d,f · Barker C.N.c · Yanovski J.A.b · Chrousos G.P.b
aLaboratory of Developmental Neurobiology, and bDevelopmental Endocrinology Branch, NICHD, cClinical Psychobiology Branch, and dClinical Neuroendocrinology Branch, NIMH, eDiagnostic Radiology Department, Clinical Center, National Institutes of Health, Bethesda, Md., fSchool of Nursing, University of Pittsburgh, Pittsburgh, Pa., USA
To evaluate the sleep disturbances of patients with Cushing syndrome and to examine the relationship between the sleep disturbances and plasma levels of delta-sleep-inducing peptide-like immunoreactivity (DSIP-LI), we performed three polysomnographic/endocrinological studies in patients with Cushing syndrome. In study 1, polysomnography was studied in 12 patients and 12 matched normal volunteers. In addition, DSIP-LI was measured every 30 min for 24 h in 9 patients with Cushing syndrome and 12 normal volunteers. The percentage of time spent in delta sleep (stages 3 and 4) was significantly reduced in patients with Cushing syndrome (5.8 ± 1.4%; mean ± SEM) compared to normal volunteers (14.0 ± 2.5%) (p < 0.01). REM sleep indices, however, were not significantly different between the two groups. There was a significant negative correlation between amount of delta sleep and 08.00 h DSIP-LI (r = –0.43, p < 0.05), which is against the notion of a causal relationship between DSIP-LI and delta sleep. The circadian rhythm of plasma DSIP-LI was found to be similar in Cushing patients and normal volunteers. In study 2, we measured plasma levels of delta-sleep-inducing peptide-like immunoreactivity (DSIP-LI) at 08.00 h in 65 patients with Cushing syndrome and 49 normal volunteers. The 08.00 h DSIP-LI concentrations of 797 ± 57 pmol/l (mean ± SEM) in the patients with Cushing syndrome were significantly reduced compared to the level of 1,062 ± 99 pmol/l found in the normal volunteers (p < 0.05). In study 3, plasma was drawn simultaneously from the petrosal sinuses and peripheral veins of Cushing patients. No central-to-peripheral gradient for plasma DSIP-LI was noted and neither peripheral, nor central plasma DSIP-LI was affected by administration of intravenous ovine CRH. We conclude that patients with Cushing syndrome have less delta sleep and lower plasma concentrations of DSIP-LI than normal controls, however a causal relationship between the two appears to be unlikely. The pituitary does not appear to be the site of synthesis of plasma DSIP, whose source remains unknown.
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