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Disruption of the Diurnal Rhythm of Plasma Melatonin in Cirrhosis

Petra E. Steindl; Barry Finn; Bernard Bendok; Steven Rothke; Phyllis C. Zee; and Andres T. Blei
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From Northwestern Memorial Hospital, Lakeside Veterans Affairs Medical Center, and the Rehabilitation Institute, Chicago, Illinois. Requests for Reprints: Andres T. Blei, MD, Lakeside Veterans Affairs Medical Center, 333 East Huron Street, Department of Medicine 111E, Chicago, IL 60611. Acknowledgments: The authors thank Drs. Eve Van Cauter and Fred Turek for their valuable criticism. Grant Support: In part by a Merit Review from the Veterans Administration Research Service; the Northwestern Memorial Foundation; and grant RR 00048 from the National Institutes of Health.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;123(4):274-277. doi:10.7326/0003-4819-123-4-199508150-00005
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Objectives: To assess 24-hour plasma melatonin profile as a marker of output rhythm from the circadian clock and to study sleep diaries as reflections of subjective sleep quality in patients with liver cirrhosis.

Design: Prospective cohort study.

Setting: Clinical research center in a university hospital.

Patients: Seven patients with cirrhosis but not alcoholism and seven age-, sex-, and education-matched controls.

Measurements: Neuropsychological testing to confirm subclinical hepatic encephalopathy. Plasma melatonin levels measured every 30 minutes for 24 hours by radioimmunoassay. Sleep diaries kept for 1 week before admission.

Results: Patients with cirrhosis had markedly elevated melatonin levels during daytime hours; in addition, the time of onset of melatonin increase and the time at which melatonin levels peaked were consistently and significantly delayed in these patients. Sleep diaries indicated more nocturnal awakenings and more frequent daytime naps in patients with cirrhosis.

Conclusion: Disruption of the diurnal rhythm of melatonin may reflect alterations of circadian function that could contribute to the disturbances of the sleep-wake cycle frequently seen in patients with cirrhosis.


Grahic Jump Location
Figure 1.
Time of onset of melatonin secretion and time of peak plasma melatonin levels. Top.nBottom.nPP

Time of onset of melatonin secretion in patients ( = 6) was significantly displaced from 7:50 p.m. ± 26 min to 9:30 p.m. ± 13 min. Time of peak plasma melatonin levels ( = 6) was significantly displaced from 12:36 a.m. ± 33 min to 5:36 a.m. ± 29 min. Horizontal bar represents the mean. * indicates = 0.013; ** indicates < 0.001.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Plasma melatonin levels (mean ±SE) expressed in pg/mL and measured at 30-minute intervals for 24 hours.P

Vertical dashed line indicates midnight. Levels were significantly higher in patients than in controls at every measurement point between 2:30 a.m. and 10:00 a.m. ( < 0.05).

Grahic Jump Location




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