Download PDF
Horm Metab Res 2021; 53(09): 608-615
DOI: 10.1055/a-1542-8816
Endocrine Care

Cushing Syndrome is Associated with Increased Stage N2 Sleep and Decreased SWS Partially Reversible After Treatment

Sevda Ismailogullari
1   Department of Neurology, Erciyes University Medical School, Kayseri, Turkey
,
Zuleyha Karaca
2   Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
,
Sedat Tarik Firat
2   Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
,
Kursad Unluhizarci
2   Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey
,
Fahrettin Kelestimur
3   Department of Endocrinology, Yeditepe University Medical School, Kayseri, Turkey
› Author Affiliations Funding Information The study was supported by Erciyes University Scientific Research Council (TTU-2013-4566).
› Further Information
Also available at
    Permissions and Reprints

Abstract

The aim of the present study was to evaluate the sleep parameters of patients with Cushing syndrome (CS) at the time of diagnosis and 12-months after treatment. Thirty four newly diagnosed patients with endogenous CS (17 with ACTH-secreting pituitary adenoma, 17 with adrenal CS) and 23 controls with similar age were included in the study. Two polysomnography (PSG) recordings were performed; one at the time of diagnosis and the other 12 months after resolution of hypercortisolemia. Control group had only baseline PSG. Based on the PSG findings, stage N2 sleep was found to be prolonged, stage N3 and REM sleep were shortened in patients with CS. Average heart rate and mean Apnea Hypopnea Index (AHI) score were higher in patients with CS than the control subjects. Sixteen (47.1%) patients with CS and 4 (17.4%) controls had obstructive sleep apnea (OSA; AHI ≥5). There were no significant differences in sleep parameters of patients according to the etiology of CS (adrenal vs. pituitary) patients. Following 12-months of treatment, a significant decrease in stage N2 sleep and a significant increase in stage N3 sleep were detected, but there was no change in terms of AHI. In conclusion, Cushing syndrome has disturbing effects on sleep structure and these effects are at least partially reversible after treatment. However, the increased risk of OSA was not reversed a year after treatment indicating the importance of early diagnosis and treatment of CS.

Key words

Cushing syndrome - cortisol - ACTH - sleep - OSA - pituitary - adrenal


Publication History

Received: 01 April 2021

Accepted after revision: 24 June 2021

Article published online:
08 September 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Wu Y, Wang L, Yang F. et al. Neural circuits for sleep-wake regulation. In: Neural Circuits of Innate Behaviors. Berlin: Springer; 2020: 91-112
    CrossrefGoogle Scholar
  • 2 Buckley TM, Schatzberg AF. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab 2005; 90: 3106-3114
    CrossrefPubMedGoogle Scholar
  • 3 Watts AG, Tanimura S, Sanchez-Watts G. Corticotropin-releasing hormone and arginine vasopressin gene transcription in the hypothalamic paraventricular nucleus of unstressed rats: daily rhythms and their interactions with corticosterone. Endocrinology 2004; 145: 529-540
    CrossrefPubMedGoogle Scholar
  • 4 Holsboer F, Von Bardeleben U, Steiger A. Effects of intravenous corticotropin-releasing hormone upon sleep-related growth hormone surge and sleep EEG in man. Neuroendocrinology 1988; 48: 32-38
    CrossrefPubMedGoogle Scholar
  • 5 Steiger A, Guldner J, Knisatschek H. et al. Effects of an ACTH/MSH (4–9) analog (HOE 427) on the sleep EEG and nocturnal hormonal secretion in humans. Peptides 1991; 12: 1007-1010
    CrossrefPubMedGoogle Scholar
  • 6 Steiger A. Neurochemical regulation of sleep. J Psychiatr Res 2007; 41: 537-552
    CrossrefPubMedGoogle Scholar
  • 7 GarcIa-Borreguero D, Wehr TA, Larrosa O. et al. Glucocorticoid replacement is permissive for rapid eye movement sleep and sleep consolidation in patients with adrenal insufficiency. J Clin Endocrinol Metab 2000; 85: 4201-4206
    PubMedGoogle Scholar
  • 8 Vgontzas AN, Bixler EO, Papanicolaou DA. et al. Rapid eye movement sleep correlates with the overall activities of the hypothalamic-pituitary-adrenal axis and sympathetic system in healthy humans. J Clin Endocrinol Metab 1997; 82: 3278-3280
    CrossrefPubMedGoogle Scholar
  • 9 Mednick SC, McDevitt EA, Walsh JK. et al. The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study. J Neurosci 2013; 33: 4494-4504
    CrossrefPubMedGoogle Scholar
  • 10 Antonenko D, Diekelmann S, Olsen C. et al. Napping to renew learning capacity: enhanced encoding after stimulation of sleep slow oscillations. Eur J Neurosci 2013; 37: 1142-1151
    CrossrefPubMedGoogle Scholar
  • 11 Baran B, Mantua J, Spencer RM. Age-related changes in the sleep-dependent reorganization of declarative memories. J Cogn Neurosci 2016; 28: 792-802
    CrossrefPubMedGoogle Scholar
  • 12 Scarpelli S, Bartolacci C, D’Atri A. et al. The functional role of dreaming in emotional processes. Front Psychol 2019; 10: 459
    CrossrefPubMedGoogle Scholar
  • 13 Arnaldi G, Mancini T, Tirabassi G. et al. Advances in the epidemiology, pathogenesis, and management of Cushing’s syndrome complications. J Endocrinol Invest 2012; 35: 434-448
    CrossrefPubMedGoogle Scholar
  • 14 Lacroix A, Feelders RA, Stratakis CA. et al. Cushing’s syndrome. Lancet 2015; 386: 913-927
    CrossrefPubMedGoogle Scholar
  • 15 Krieger DT, Glick SM. Sleep EEG stages and plasma growth hormone concentration in states of endogenous and exogenous hypercortisolemia or ACTH elevation. J Clin Endocrinol Metab 1974; 39: 986-1000
    CrossrefPubMedGoogle Scholar
  • 16 Shipley JE, Schteingart DE, Tandon R. et al. Sleep architecture and sleep apnea in patients with Cushing’s disease. Sleep 1992; 15: 514-518
    CrossrefPubMedGoogle Scholar
  • 17 Friedman TC, García-Borreguero D, Hardwick D. et al. Decreased delta-sleep and plasma delta-sleep-inducing peptide in patients with Cushing syndrome. Neuroendocrinology 1994; 60: 626-634
    CrossrefPubMedGoogle Scholar
  • 18 Shipley JE, Schteingart DE, Tandon R. et al. EEG sleep in Cushing’s disease and Cushing’s syndrome: comparison with patients with major depressive disorder. Biol Psychiatry 1992; 32: 146-155
    CrossrefPubMedGoogle Scholar
  • 19 D’Angelo V, Beccuti G, Berardelli R. et al. Cushing’s syndrome is associated with sleep alterations detected by wrist actigraphy. Pituitary 2015; 18: 893-897
    CrossrefPubMedGoogle Scholar
  • 20 D’Aurea C, Poyares D, Piovezan RD. et al. Objective short sleep duration is associated with the activity of the hypothalamic-pituitary-adrenal axis in insomnia. Arq Neuropsiq 2015; 73: 516-519
    CrossrefPubMedGoogle Scholar
  • 21 Ismailogullari S, Bolattürk OF, Karaca Z. et al. Dynamic evaluation of the hypothalamic–pituitary–adrenal and growth hormone axes and metabolic consequences in chronic insomnia; a case–control study. Sleep Biol Rhythms 2017; 15: 317-326
    CrossrefPubMedGoogle Scholar
  • 22 Starkman MN. Neuropsychiatric findings in Cushing syndrome and exogenous glucocorticoid administration. Endocrinol Metab Clin 2013; 42: 477-488
    CrossrefPubMedGoogle Scholar
  • 23 Gokosmanoğlu F, Güzel A, Kan EK. et al. Increased prevalence of obstructive sleep apnea in patients with Cushing’s syndrome compared with weight-and age-matched controls. Eur J Endocrinol 2017; 176: 267-272
    CrossrefPubMedGoogle Scholar
  • 24 Wang L-U, Wang T-Y, Bai Y-M. et al. Risk of obstructive sleep apnea among patients with Cushing’s syndrome: a nationwide longitudinal study. Sleep Med 2017; 36: 44-47
    CrossrefPubMedGoogle Scholar
  • 25 Nieman LK, Biller BM, Findling JW. et al. The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 1526-1540
    CrossrefPubMedGoogle Scholar
  • 26 Nieman LK, Biller BM, Findling JW. et al. Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015; 100: 2807-2831
    CrossrefPubMedGoogle Scholar
  • 27 Berry RB, Budhiraja R, Gottlieb DJ. et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. J Clin Sleep Med 2012; 8: 597-619
    CrossrefPubMedGoogle Scholar
  • 28 Romanowski CP, Fenzl T, Flachskamm C. et al. Central deficiency of corticotropin-releasing hormone receptor type 1 (CRH-R1) abolishes effects of CRH on NREM but not on REM sleep in mice. Sleep 2010; 33: 427-436
    CrossrefPubMedGoogle Scholar
  • 29 Born J, DeKloet E, Wenz H. et al. Gluco-and antimineralocorticoid effects on human sleep: a role of central corticosteroid receptors. Am J Physiol Endocrinol Metab 1991; 260: E183-E188
    CrossrefPubMedGoogle Scholar
  • 30 Steiger A, Pawlowski M. Depression and sleep. Int J Mol Sci 2019; 20: 607
    CrossrefPubMedGoogle Scholar
  • 31 Karaca Z, Ismailogullari S, Korkmaz S. et al. Obstructive sleep apnoea syndrome is associated with relative hypocortisolemia and decreased hypothalamo–pituitary–adrenal axis response to 1 and 250 μg ACTH and glucagon stimulation tests. Sleep Med 2013; 14: 160-164
    CrossrefPubMedGoogle Scholar
  • 32 Cizza G, de Jonge L, Piaggi P. et al. Neck circumference is a predictor of metabolic syndrome and obstructive sleep apnea in short-sleeping obese men and women. Metab Syndr Relat Disord 2014; 12: 231-241
    CrossrefPubMedGoogle Scholar
  • 33 Davies R, Ali N, Stradling J. Neck circumference and other clinical features in the diagnosis of the obstructive sleep apnoea syndrome. Thorax 1992; 47: 101-105
    CrossrefPubMedGoogle Scholar
  • 34 Grunstein R, Wilcox I, Yang T-S. et al. Snoring and sleep apnoea in men: association with central obesity and hypertension. Int J Obes Relat Metab Disord 1993; 17: 533-540
    PubMedGoogle Scholar
  • 35 Yanovski JA, Cutler GB. Glucocorticoid action and the clinical features of Cushing’s syndrome. Endocrinol Metab Clin North Am 1994; 23: 487-509
    CrossrefPubMedGoogle Scholar
  • 36 Milani P, Piu P, Popa T. et al. Cortisol-induced effects on human cortical excitability. Brain Stimul 2010; 3: 131-139
    CrossrefPubMedGoogle Scholar
  • 37 Baudry S, Lanfranco F, Merletti R. et al. Effects of short-term dexamethasone administration on corticospinal excitability. Med Sci Sports Exerc 2014; 46: 695-701
    CrossrefPubMedGoogle Scholar
  • 38 Hall ED, Braughler JM. Glucocorticoid mechanisms in acute spinal cord injury: A review and therapeutic rationale. Surg Neurol 1982; 18: 320-327
    CrossrefPubMedGoogle Scholar