The relations of circulating agouti-related peptide and leptin with altered sleep architecture in patients with active Cushing’s disease: a pilot study

• Published in: Journal of endocrinological investigation Vol. 47; no. 1; pp. 167 - 178
• Main Authors: Sulu, C., Senel, G. B., Koca, O., Alaylioglu, M., Demir, A. N., Durcan, E., Ak, D. G., Dursun, E., Konukoglu, D., Ozkaya, H. M., Karadeniz, D., Kadioglu, P.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2024; Springer Nature B.V
• Subjects: Adrenocorticotropic hormone; Agouti-Related Protein; Apnea; Body mass index; Efficiency; Endocrinology; Humans; Internal Medicine; Leptin; Medicine; Medicine & Public Health; Metabolic Diseases; Nervous system diseases; Original Article; Peptides; Pilot Projects; Pituitary; Pituitary ACTH Hypersecretion; Quality of Life; Sleep; Sleep and wakefulness; Sleep disorders; Agouti-related peptide; Cortisol; Sleep; Cushing’s disease; Leptin
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-023-02133-0

Aim To 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. Methods We 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. Results The 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). Conclusions Active 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.