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).(ABSTRACT TRUNCATED AT 250 WORDS)