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.

Automated summary

This study aimed to evaluate the sleep architecture of patients with Cushing's disease (CD) and investigate the role of agouti-related peptide (AgRP) and/or leptin in sleep alterations in patients with active CD. Polysomnography was performed on 26 patients with active CD and compared with age and sex-matched control subjects. The results showed that patients with CD had reduced sleep efficiency and increased wake after sleep onset, and their serum levels of AgRP and leptin were elevated. These findings suggest that CD is associated with impaired sleep efficiency and continuity, which may be influenced by elevated levels of AgRP and leptin.