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Impaired Hepatic Catabolism of Melatonin in Cirrhosis
- Petra E. Steindl, MD;
- Peter Ferenci, MD; and
- Wolfgang Marktl, MD
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TO THE EDITOR:
Prompted by Garfinkel and Zisapel's comment [1] on our paper, published in August 1995 [2], we present some consecutive data. We postulated that elevated plasma melatonin levels and an altered 24-hour profile of the hormone we found in patients with liver cirrhosis [2] could represent an altered output of the circadian clock [3], causing a central disturbance of circadian rhythmicity.
Garfinkel and Zisapel suggested that we measure the urinary metabolite of melatonin, 6-sulfatoxymelatonin, to determine whether increased production in the pineal gland or decreased catabolism by the liver is the main reason for elevated serum melatonin levels in patients with liver cirrhosis.
We therefore measured urinary 6-sulfatoxymelatonin levels in 21 hospitalized cirrhotic patients with normal renal function (14 men and 7 women; median age, 50 years [range, 29 to 80 years]; Child class A, 7 patients; class B, 11 patients; class C, 3 patients) and in 9 healthy persons (3 men and 7 women; median age, 49 years [range, 32 to 69 years]). Sixteen had alcoholic liver disease, 2 had hepatitis C, and 1 each had primary biliary cirrhosis and Wilson disease. Two patients had signs of clinically overt hepatic encephalopathy.
Eight-hour urine excretion (10:00 p.m. to 6:00 a.m.) was assayed for 6-sulfatoxymelatonin by enzyme-linked immunosorbent assay (Melatonin-Sulfat-ELISA, IBL Ges mbH, Hamburg, Germany). Routine laboratory testing was performed by using standard methods. Statistical analysis was done with the paired Student t-test or the Mann-Whitney rank-sum test.
In the 8-hour urine measurements, cirrhotic patients had a significantly decreased concentration (mean ± SE, 19.01 ± 2.76 ng/mL compared with 39.2 ± 5.41; P = 0.001) and total excretion (median, 8.28 mg [range, 0.85 to 28.1 mg] compared with 12.21 mg [range, 9.12 to 29.04 mg]; P < 0.05) of 6-sulfatoxymelatonin, compared with controls (Figure 1). Urine volumes were similar in the two groups. No correlation to Child class or liver function measures was seen.
These findings indicate that the elevated plasma melatonin levels seen in cirrhotic patients are at least partly due to impaired hepatic catabolism.
Petra E. Steindl, MD
Peter Ferenci, MD
Wolfgang Marktl, MD
University of Vienna; Vienna, Austria
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
