Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men

J Clin Endocrinol Metab. 2014 Aug;99(8):2861-8. doi: 10.1210/jc.2013-4254. Epub 2014 May 13.


Context: Insufficient sleep is associated with increased cardiometabolic risk. Alterations in hypothalamic-pituitary-adrenal axis may underlie this link.

Objective: Our objective was to examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations.

Methods: Thirteen subjects participated in 2 laboratory sessions (2 nights of 10 hours in bed versus 2 nights of 4 hours in bed) in a randomized crossover design. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 9:00 am to midnight to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 2:00 pm to midnight to measure free cortisol. Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales.

Results: Sleep restriction was associated with a 19% increase in overall ACTH levels (P < .03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .02). Overall total cortisol levels were also elevated (+21%; P = .10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (-21%; P < .05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol.

Conclusion: The impact of sleep loss on hypothalamic-pituitary-adrenal activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Circadian Rhythm
  • Cross-Over Studies
  • Health
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Male
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiopathology*
  • Sleep / physiology
  • Sleep Deprivation / metabolism
  • Sleep Deprivation / physiopathology*
  • Time Factors
  • Young Adult


  • Adrenocorticotropic Hormone
  • Hydrocortisone