The Relations of Circulating Agouti-Related Peptide and Leptin with Altered Sleep Architecture in Patients with Active Cushing's Disease: a Pilot Study

AimTo evaluate sleep architecture of patients with Cushing's disease (CD) and to explore whether agouti-related peptide (AgRP) and/or leptin play a permissive role in sleep alterations in patients with active CD.MethodsWe performed polysomnography on 26 patients with active CD and age 26 age- and sex-matched control subjects. Blood samples were obtained from all participants for the analyzes of AgRP and leptin. The laboratory and sleep-related parameters were compared.ResultsThe groups were similar in age, gender, and body mass index. The CD group had reduced sleep efficiency (71.6 +/- 12.1% vs. 78.8 +/- 12.6%, p = 0.042) and increased wake after sleep onset (WASO%) (24.7 +/- 13.1% vs. 17.4 +/- 11.6%, p = 0.040) as compared to control group. Seventeen patients with CD (65.4%) and 18 control subjects (69.2%) had obstructive sleep apnea. Serum AgRP (13.2 +/- 7.4 pg/ml vs. 9 +/- 3.1, p = 0.029), leptin (59.5 mcg/l, [IQR] 32.6-94.6 vs. 25.3 mcg/l, [IQR] 12.9-57.5, p = 0.007) were higher in CD group. AgRP and leptin correlated negatively with total sleep time, sleep efficiency, stage N2 sleep (%), and positively with WASO%. In multiple regression analyses, serum cortisol (ss = - 0.359, p = 0.042) and AgRP (ss = - 0.481, p = 0.01) were significant predictor of sleep efficiency. AgRP was also significant predictor of WASO% (ss = 0.452 and p < 0.05).ConclusionsActive CD carries an increased risk of impaired sleep efficiency and continuity which may worsen health-related quality of life. Elevated circulating AgRP and, to a lesser extent, leptin may be associated with decreased sleep efficiency and continuity in patients with CD. Patients with CD who have subjective sleep symptoms should be screened with polysomnography.