Original Paper Horm Res 1998;50:197–204 Circadian Plasma Leptin Levels in Patients with Anorexia nervosa: Relation to Insulin and Cortisol Stephan Herpertz a Richard Wagner b Norbert Albers c Werner F. Blum d, e Barbara Pelz a Mathias Langkafel a Werner Köpp f Andreas Henning a Corinna Oberste-Berghaus b Klaus Mann b Wolfgang Senf a Johannes Hebebrand g a Clinic of Psychotherapy and Psychosomatics, University of Essen, b Department of Endocrinology, Medical Clinic, University of Essen, c Children’s Hospital, University of Bonn, d Children’s Hospital, University of Giessen, e Lilly Germany, Bad Homburg, f Department of Psychosomatics and Psychotherapy, Benjamin Franklin University Berlin, g Clinical Research Group, Department of Child and Adolescent Psychiatry, University of Marburg, Germany OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO Key Words Leptin Anorexia nervosa Phase shift Circadian rhythmicity OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO Abstract In anorexia nervosa, underweight results from a loss of body mass due to a restricted energy intake. Circulating leptin levels have been shown to be low in the acute stage of the disorder. We studied diurnal secretion characteristics of leptin, insulin and cortisol in a study group of anorectic patients prior to refeeding, a second study group of anorectic patients after initiation of refeed- ing and study groups of healthy underweight and normal-weight controls. Spontaneous secretion of leptin, insulin and cortisol was measured by drawing blood samples every 2 h for 24 h. The temporal relationships between the diurnal secretion patterns of the three hormones were assessed by cross-corre- lation analysis in every study group. Plasma levels of leptin and cortisol were secreted with a specific circadian rhythmicity and displayed an intricate tem- poral relationship in anorectic patients. Semistarvation in the non-refed patients was associated with (1) exceedingly low plasma leptin levels, (2) a qualitative alteration in the circadian rhythm of leptin and cortisol levels and (3) an alteration in the temporal coupling between cortisol and leptin. In con- trast, in the patients who had gained weight, leptin levels were higher; further- more, the diurnal pattern of leptin and the temporal relationship between lep- tin and cortisol were similar to controls. Increments in insulin secretion pre- ceded those of leptin by 4–6 h in both anorectic patients and in controls. Lep- tin levels increased 4 h prior to those of cortisol in controls and in refed patients, whereas in the non-refed patients cortisol increased prior to leptin. Thus, anorexia nervosa leads to pronounced, albeit reversible changes in the secretion dynamics of leptin and cortisol. Received: January 23, 1998 Accepted after revision: June 16, 1998 Stephan Herpertz, MD Clinic of Psychotherapy and Psychosomatics University of Essen, Postfach 103043 D–45030 Essen (Germany) Tel. +49 201 7227 223, Fax +49 201 7227 304, E-Mail stephan.herpertz@uni-essen.de ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 1998 S. Karger AG, Basel 0301–0163/98/0504–0197$15.00/0 Accessible online at: http://BioMedNet.com/karger Presented in part at the European Leptin Symposium in Giessen, Germany, April–May 1997.