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Cited by 127Stress Responses and CortisolSleep and Work-Related FatigueSleep and Wakefulness Research

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

Open access
Guyon, A., Balbo, M., Morselli, L. L., Tasali, E., Leproult, R., L'Hermite-Balériaux, M., Van Cauter, E., Spiegel, K.·2014·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2013-4254PMC PMC4121029
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Abstract

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.

AI snapshot

Written from the paper’s full text.

TL;DR

Two nights of sleep restriction to 4 hours in bed increased daytime HPA-axis activity in healthy young men, with higher overall ACTH and a trend toward higher total cortisol. The effect varied by time of day: morning ACTH rose without cortisol, while evening total and free cortisol rose without ACTH, dampening the circadian cortisol decline.

Key findings

  • Sleep restriction increased overall daytime ACTH by 19% (P < .03) and total cortisol by 21% (P = .10); the ACTH increase correlated with the amount of sleep loss (rSp = 0.63, P < .02).
  • Morning ACTH was 10% higher after sleep restriction (P < .04) without a significant morning cortisol elevation, whereas evening total cortisol increased by 30% (P < .03) and evening free cortisol by 200% (P < .04) without an evening ACTH increase.
  • The circadian decline in total cortisol was dampened by 21% (P < .05); pulse frequency was unchanged for ACTH and cortisol, though ACTH pulse trough and peak values were higher (both P < .05).
  • Perceived stress did not differ between conditions, but increased appetite correlated with increased total cortisol (rSp = 0.67, P < .04; hunger rSp = 0.60, P < .06).

Methods

  • Thirteen healthy young men (median age 21 [20; 23] years; BMI 24.6 [21; 25] kg/m²) completed a randomized crossover study with two laboratory sessions: 2 nights of 10 hours in bed vs 2 nights of 4 hours in bed, spaced at least 6 weeks apart.
  • After the second night of each session, blood was sampled every 20 minutes from 9:00 am to midnight for ACTH and total cortisol, and saliva every 20 minutes from 2:00 pm to midnight for free cortisol; participants received constant glucose infusion and remained recumbent.
  • Analyses used Wilcoxon exact rank tests, mixed-effects ANOVA for serial hormone data, Spearman correlations, and the ULTRA algorithm for pulse detection.

Limitations

  • The paper states: small sample size; only young men, so findings cannot be extrapolated to the general population; constant glucose infusion instead of meals does not mimic real-life conditions; and sleep restriction lasted only 2 nights, so results may not translate to chronic sleep debt.
  • Evident from the text: the controlled laboratory setting and exclusion of women, smokers, and medicated individuals limit generalizability to everyday sleep restriction contexts.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1210/jc.2013-4254

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 78 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Abstract

    Evening ACTH levels were unchanged after sleep restriction.

    “In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    Morning cortisol levels were not elevated after sleep restriction.

    “Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    Evening total cortisol increased by 30% after sleep restriction (P < .03).

    “In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    Pulse frequency was unchanged for both ACTH and cortisol after sleep restriction.

    “Pulse frequency was unchanged for both ACTH and cortisol.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Abstract

    Morning ACTH levels were higher after sleep restriction (P < .04).

    “Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol.”
    Quote in the paperSubstantial claim
  • May combine two claims. 24
  • Classified as probably not a substantial claim. 28

  • May combine two claims.

    Findingown data
    § Abstract

    Overall total cortisol levels were elevated by 21% after sleep restriction, but the difference was not statistically significant (P = .10).

    “Overall total cortisol levels were also elevated (+21%; P = .10).”
    • Also stated in: § Results · hedged
      “there was a trend for a similar increase (ie, +21% [−6%; +41%]) in total cortisol (6844 [6308; 7324] vs 4826 [4519; 7240] μg/dL/min, P = .10)”
    • Also stated in: § Results · hedged
      “with a trend for increased overall serum cortisol (F = 3.0, P = .11)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results

    The reduction in TST was not correlated with increase in total cortisol (rSp = -0.27, P = .36) or free cortisol (rSp = -0.20, P = .52).

    “but not of total (rSp = −0.27, P = .36) or free cortisol (rSp = −0.20, P = .52).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Results

    Similar results for perceived stress scores were obtained in the morning and evening.

    “Similar results were obtained when we analyzed scores obtained in the morning (9:00 am to 1:00 pm, 7 [6; 8] vs 7 [6; 8], P = .27, 2 [1; 3] vs 2 [1; 3], P = .27; and 1 [1; 2] vs 1 [1; 2], P = .50) or in the evening (8:00 pm to midnight; P > .34).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results

    Overall mean scores for calm, tense, and nervous were similar in both sleep conditions (P = .42, .15, .34 respectively).

    “The overall mean scores for calm, tense and nervous were similar in both sleep conditions (7 [5; 8] vs 7 [6; 8], P = .42; 2 [1; 3] vs 2 [1;3], P = .15; and 1 [1; 1] vs 1 [1; 1[, P = .34, respectively).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    The daily variations of cortisol after sleep restriction are characterized by an increase in evening total (+30%) and free cortisol levels (+200%).

    “The resulting daily variations of cortisol are characterized by an increase in evening total (+30%) and free cortisol levels (+200%).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results

    Over the entire sampling period, the number of ACTH pulses and the number, mean trough, peak, and absolute increment of pulses of total and free cortisol were unaffected by the sleep condition.

    “Over the entire sampling period, the number of ACTH pulses as well as the number, mean trough, and peak and absolute increment of pulses of total and free cortisol were unaffected by the sleep condition.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation
    § Discussion

    Consistent with our previous study of 6 nights of sleep restriction, levels of perceived stress in the present study remained low and were not affected by sleep loss.

    “Consistent with our previous study of 6 nights of sleep restriction (15), we found that levels of perceived stress in the present study remained low and were not affected by sleep loss.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Spiegel, 2004, Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin, J Clin Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Abstract

    Habitual short sleep, usually 6 hours or less, is linked in epidemiological studies to increased mortality and increased prevalence and incidence of numerous pathological conditions including obesity, diabetes, cardiovascular diseases, vulnerability to infection, depression, and anxiety.

    “Habitual short sleep, usually 6 hours or less, has been linked in epidemiological studies to increased mortality and increased prevalence and incidence of numerous pathological conditions including obesity, diabetes, cardiovascular diseases, vulnerability to infection, depression, and anxiety (3–10).”
    Quote in the paperNot a substantial claim0 of 8 sources checked
    • cites [3] Spiegel, 2009, Effects of poor and short sleep on glucose metabolism and obesity risk, Nat Rev

      Not checked in the free run.

    • cites [4] Cappuccio, 2010, Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis, Diabetes Care source

      Not checked in the free run.

    • cites [5] Cappuccio, 2011, Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies, Eur Heart J source

      Not checked in the free run.

    • cites [6] Nielsen, 2011, Short sleep duration as a possible cause of obesity: critical analysis of the epidemiological evidence, Obes Rev source

      Not checked in the free run.

    • cites [7] Morselli, 2012, Sleep and metabolic function, Pflugers Arch source

      Not checked in the free run.

    • cites [8] Faraut, 2012, Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery, Sleep Med Rev source

      Not checked in the free run.

    • cites [9] Cappuccio, 2013, Sleep and mortality: cause, consequence, or symptom?, Sleep Med source

      Not checked in the free run.

    • cites [10] Alvaro, 2013, A systematic review assessing bidirectionality between sleep disturbances, anxiety, and depression, Sleep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Abstract

    Not only the levels of cortisol but also its variation across the day play a role for health and disease.

    “Indeed, not only the levels of cortisol but also its variation across the day play a role for health and disease (20, 21).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [20] Chung, 2011, Circadian rhythm of adrenal glucocorticoid: its regulation and clinical implications, Biochim Biophys Acta source

      Not checked in the free run.

    • cites [21] Plat, 1999, Metabolic effects of short-term elevations of plasma cortisol are more pronounced in the evening than in the morning, J Clin Endocrinol Metab

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Abstract

    Another study examined the impact of 2 nights of 4 hours in bed versus 2 nights of 8 hours in bed and found no differences in either ACTH or cortisol.

    “The other examined the impact of 2 nights of 4 hours in bed vs 2 nights of 8 hours in bed and found no differences in either ACTH or cortisol (22).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Schmid, 2011, Disturbed glucoregulatory response to food intake after moderate sleep restriction, Sleep source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data
    § Abstract

    The two sleep conditions were administered in randomized order in a crossover design.

    “the subjects participated in 2 laboratory sessions in randomized order.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given
    § Abstract

    Insufficient sleep is associated with increased cardiometabolic risk.

    “Insufficient sleep is associated with increased cardiometabolic risk.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Abstract

    Perceived stress, hunger, and appetite were assessed using validated scales.

    “Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [23] Monk, 1989, A visual analogue scale technique to measure global vigor and affect, Psychiatry Res source

      Not checked in the free run.

    • cites [24] Clark, 1989, Diurnal variation in the positive affects, Motivation Emotion source

      Not checked in the free run.

    • cites [25] Stubbs, 2000, The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings, Br J Nutr source

      Not checked in the free run.

    • cites [26] Fernstrom, 1987, Appetite and food preference in depression: effects of imipramine treatment, Biol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Abstract

    For each hormone, all samples from the same subject were measured in the same assay.

    “For each hormone, all samples from the same subject were measured in the same assay.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation
    § Abstract

    Plasma ACTH and serum cortisol were measured by immunochemiluminometric assay with intra-assay coefficients of variation of 9.6% or less and 5% on average, respectively.

    “Plasma ACTH and serum cortisol were measured by immunochemiluminometric assay (Immulite; Siemens). The limit of sensitivity of the ACTH assay was 1 pg/mL, and the coefficient of intra-assay variation was ≤9.6%. The limit of sensitivity of the cortisol assay was 1.0 μg/dL, and the coefficient of intra-assay variation was 5% on average (21).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Plat, 1999, Metabolic effects of short-term elevations of plasma cortisol are more pronounced in the evening than in the morning, J Clin Endocrinol Metab

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Premisenone given
    § Abstract

    A complete assessment of the hypothalamic-pituitary-adrenal axis requires measurement of both ACTH and cortisol levels at frequent intervals across the day.

    “A complete assessment of the HPA axis requires the measurement of both ACTH and cortisol levels at frequent intervals across the day.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Abstract

    The hypothalamic-pituitary-adrenal axis regulates a wide range of physiologic processes.

    “Because the hypothalamic-pituitary-adrenal (HPA) axis regulates a wide range of physiologic processes and is affected by experimental sleep restriction, it is a putative key mediator of the adverse health effects of insufficient sleep (3–11).”
    Quote in the paperSubstantial claim0 of 9 sources checked
    • cites [3] Spiegel, 2009, Effects of poor and short sleep on glucose metabolism and obesity risk, Nat Rev

      Not checked in the free run.

    • cites [4] Cappuccio, 2010, Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis, Diabetes Care source

      Not checked in the free run.

    • cites [5] Cappuccio, 2011, Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies, Eur Heart J source

      Not checked in the free run.

    • cites [6] Nielsen, 2011, Short sleep duration as a possible cause of obesity: critical analysis of the epidemiological evidence, Obes Rev source

      Not checked in the free run.

    • cites [7] Morselli, 2012, Sleep and metabolic function, Pflugers Arch source

      Not checked in the free run.

    • cites [8] Faraut, 2012, Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery, Sleep Med Rev source

      Not checked in the free run.

    • cites [9] Cappuccio, 2013, Sleep and mortality: cause, consequence, or symptom?, Sleep Med source

      Not checked in the free run.

    • cites [10] Alvaro, 2013, A systematic review assessing bidirectionality between sleep disturbances, anxiety, and depression, Sleep source

      Not checked in the free run.

    • cites [11] Chrousos, 2007, Glucocorticoid action networks and complex psychiatric and/or somatic disorders, Stress source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Abstract

    Napping during the outpatient periods was minimal: only 4 naps, lasting 121 minutes in total, were detected in the 4-hours-in-bed condition in a single subject.

    “only 4 naps, lasting 121 minutes in total, were detected in the 4-hours-in-bed condition in a single subject.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data
    § Abstract

    Prestudy time in bed and total sleep time did not differ between the two experimental conditions.

    “Prestudy TIB and TST did not differ between the 2 experimental conditions (P = .16 and P = .42, respectively).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given
    § Abstract

    Alterations in the hypothalamic-pituitary-adrenal axis may underlie the link between insufficient sleep and increased cardiometabolic risk.

    “Alterations in hypothalamic-pituitary-adrenal axis may underlie this link.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Abstract

    One study found increased evening cortisol levels in the face of unchanged ACTH levels after 5 nights of 4 hours in bed in comparison with 2 nights of 10 hours in bed.

    “One study found increased evening cortisol levels in the face of unchanged ACTH levels after 5 nights of 4 hours in bed in comparison with 2 nights of 10 hours in bed (19).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Reynolds, 2012, Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men, PloS One source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning
    § Abstract

    Blood sampling started 1 hour after catheter insertion to avoid the effect of venipuncture stress on ACTH and cortisol levels.

    “Sampling started 1 hour after catheter insertion to avoid observing the effect of the venipuncture stress on ACTH and cortisol levels.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Abstract

    Free cortisol in saliva was measured by RIA with an intra-assay coefficient of variation averaging 4%.

    “Free cortisol in saliva was measured by RIA (Coat-A-Count; Diagnostic Products Corporation) following the manufacturer's directions. The limit of sensitivity of the assay was 0.025 μg/dL, and the coefficient of intra-assay variation averaged 4%.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § Discussion

    Participants received a constant glucose infusion instead of 3 meals, an experimental condition that does not mimic real-life conditions.

    “Third, our participants received a constant glucose infusion instead of 3 meals, an experimental condition that does not mimic real-life conditions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data
    § Discussion

    Two nights of 4 hours in bed were associated with spontaneous HPA axis hyperactivity, because overall daytime levels of ACTH were increased by 19% and total cortisol tended to increase by 21%.

    “We found that 2 nights of 4 hours in bed were associated with spontaneous HPA axis hyperactivity, because overall daytime levels of ACTH were increased by 19% and total cortisol tended to increase by 21%.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationown data
    § Discussion

    Elevated cortisol levels at a time when cortisol is usually low are likely to adversely affect the numerous physiological processes modulated by the final product of the HPA axis.

    “These elevated cortisol levels at a time when cortisol is usually low are likely to adversely affect the numerous physiological processes modulated by the final product of the HPA axis.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation
    § Discussion

    In animals, intracerebroventricular injection of orexins activates the HPA axis by increasing CRH release in the paraventricular nucleus of the hypothalamus.

    “In animals, intracerebroventricular injection of orexins activates the HPA axis by increasing CRH release in the paraventricular nucleus of the hypothalamus (35).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Rohleder, 2007, Effects of nutrition on neuro-endocrine stress responses, Curr Opin Clin Nutr Metab Care source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data
    § Discussion

    Sleep loss acts as a mild physiological, but not psychological, stressor, because measures of perceived stress remained unaffected by sleep loss.

    “Sleep loss therefore acts as a mild physiological, but not psychological, stressor, because measures of perceived stress remained unaffected by sleep loss.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § Discussion

    Sleep loss differently affected ACTH and cortisol levels according to the time of day, suggesting that sleep loss alters the circadian modulation of the sensitivity of the adrenals to ACTH.

    “In addition to this overall mild hyperactivity, we found that sleep loss differently affected ACTH and cortisol levels according to the time of day, suggesting that sleep loss alters the circadian modulation of the sensitivity of the adrenals to ACTH.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Discussion

    Orexins are synthesized by neurons in the lateral hypothalamus and stimulate arousal and feeding.

    “Orexins are synthesized by neurons in the lateral hypothalamus and stimulate arousal and feeding (36).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Mieda, 2012, Overview of orexin/hypocretin system, Prog Brain Res source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation
    § Results

    The 20-minute sampling frequency used in the study may have been insufficient to detect changes in ACTH pulse frequency.

    “It is possible that the 20-minute sampling frequency used in our study was insufficient to detect changes in ACTH pulse frequency (30).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Iranmanesh, 1990, Intensive venous sampling paradigms disclose high frequency adrenocorticotropin release episodes in normal men, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    These results suggest that adrenal sensitivity to ACTH may be reduced in the morning and enhanced in the evening in a state of sleep loss.

    “These results suggest that adrenal sensitivity to ACTH may be reduced in the morning and, as previously suggested (19), enhanced in the evening in a state of sleep loss.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Reynolds, 2012, Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men, PloS One source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data
    § Discussion

    Sleep restriction was applied for only 2 nights, and the results may not translate to states of chronic sleep debt.

    “Lastly, sleep restriction was applied for only 2 nights, and the results may not translate to states of chronic sleep debt, although in a well-documented prospective epidemiologic study in 2802 older adults, short sleep predicted higher daytime cortisol levels (42).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Kumari, 2010, Identifying patterns in cortisol secretion in an older population. Findings from the Whitehall II study, Psychoneuroendocrinology source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    The study studied only young men and the data cannot be extrapolated to the general population.

    “Second, we studied only young men and the data cannot, therefore, be extrapolated to the general population.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion

    Evidence is rapidly accumulating to indicate that misalignment between central and peripheral clocks has a host of adverse effects, including an increased risk of obesity and type 2 diabetes.

    “Evidence is rapidly accumulating to indicate that misalignment between central and peripheral clocks has a host of adverse effects, including an increased risk of obesity and type 2 diabetes (37, 39).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [37] Dickmeis, 2009, Glucocorticoids and the circadian clock, J Endocrinol source

      Not checked in the free run.

    • cites [39] Bass, 2010, Circadian integration of metabolism and energetics, Science source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Discussion

    The sample size is small.

    “First, the sample size is small.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Discussion

    The study complemented hormonal analysis with repeated assessments of self-reported levels of stress, hunger, and appetite using validated instruments.

    “Lastly, we complemented our hormonal analysis with repeated assessments of self-reported levels of stress, hunger, and appetite using validated instruments.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data
    § Discussion

    The study collected blood and saliva samples at frequent intervals throughout the day, allowing evaluation of the effects of sleep loss on both the pulsatile and circadian variations.

    “Third, we collected blood and saliva samples at frequent intervals throughout the day, allowing us to evaluate the effects of sleep loss on both the pulsatile and circadian variations.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning
    § Discussion

    Irrespective of the underlying mechanisms, these alterations in HPA functioning may mediate the association between short sleep and increased risk for various conditions, including obesity, diabetes, cardiovascular diseases, vulnerability to infection, depression, and anxiety.

    “Irrespective of the underlying mechanisms, these alterations in HPA functioning may mediate the association between short sleep and increased risk for various conditions, including obesity, diabetes, cardiovascular diseases, vulnerability to infection, depression, and anxiety.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data
    § Discussion

    The increase in cortisol levels was correlated with increased appetite, highlighting the close relationship between the regulation of arousal, energy homeostasis, and the HPA axis.

    “The increase in cortisol levels was correlated with increased appetite, highlighting the close relationship between the regulation of arousal, energy homeostasis, and the HPA axis.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning
    § Discussion

    The study assessed both ACTH and total as well as free cortisol, therefore allowing a complete assessment of the HPA axis.

    “Second, we assessed both ACTH and total as well as free cortisol, therefore allowing a complete assessment of the HPA axis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion

    In a well-documented prospective epidemiologic study in 2802 older adults, short sleep predicted higher daytime cortisol levels.

    “although in a well-documented prospective epidemiologic study in 2802 older adults, short sleep predicted higher daytime cortisol levels (42).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Kumari, 2010, Identifying patterns in cortisol secretion in an older population. Findings from the Whitehall II study, Psychoneuroendocrinology source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given
    § Discussion

    The study used a randomized crossover design with rigorously controlled experimental conditions.

    “First, we used a randomized crossover design with rigorously controlled experimental conditions.”
    Quote in the paperSubstantial claim
43 of 43

  • The paper relies on this without support.

    The role of ACTH levels in the evening elevation of cortisol secretion after sleep loss has not been elucidated.

    “The role of ACTH levels in this evening elevation of cortisol secretion has not been elucidated.”

  • The paper relies on this without support.

    Cortisol is a major internal synchronizer of central and peripheral clocks.

    “Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Partial pituitary desensitization to CRH is likely the consequence of sustained elevated CRH release.

    “Findings of elevated expression and release of CRH in sleep-deprived rodents [38][39][40] and of elevated baseline ACTH levels in sleep-deprived humans in the present and in a previous study 16 suggest that partial pituitary desensitization to CRH is likely the consequence of sustained elevated CRH release.”

    From Effects of Insufficient Sleep on Pituitary–Adrenocortical Response to CRH Stimulation in Healthy Men (2017) · cites this paper as [16]

    The Discussion (page unavailable) reports increased CRH synthesis and release alongside reduced pituitary CRH binding after sleep restriction, and the Results report elevated ACTH in the study’s participants. These findings are consistent with the proposed explanation, but the paper does not establish that sustained CRH release causes partial pituitary desensitization. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • A recent study in healthy humans reported elevated daytime ACTH levels following 2 nights of 4 hours in bed, providing evidence for up-regulation of the HPA axis during severe sleep loss in humans.

    “a recent study in healthy humans reported elevated daytime ACTH levels following 2 nights of 4 hours in bed, therefore providing evidence for an up-regulation of the HPA axis during severe sleep loss in humans.16”

    From Effects of Insufficient Sleep on Pituitary–Adrenocortical Response to CRH Stimulation in Healthy Men (2017) · cites this paper as [16]

  • Adrenal sensitivity appears to be differently affected in the morning and in the evening during sleep loss.

    “Since adrenal sensitivity appears to be differently affected in the morning and in the evening during sleep loss, 16”

    From Effects of Insufficient Sleep on Pituitary–Adrenocortical Response to CRH Stimulation in Healthy Men (2017) · cites this paper as [16]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • ACTH-sleep-loss correlation differs between abstract and results

    Minor

    The abstract reports a Spearman correlation of 0.63, while the Results section reports 0.64 for the same association between sleep loss and increased overall ACTH.

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Authors
Guyon, A., Balbo, M., Morselli, L. L., Tasali, E., Leproult, R., L'Hermite-Balériaux, M., Van Cauter, E., & Spiegel, K.
Affiliations
  • Lyon 1 Université (FR)
  • Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo (IT)
  • University of Chicago (US)
  • Université Libre de Bruxelles (BE)
  • Libre de Bruxelles, Brussels, 1050 Belgium and Faculté de Médecine (M.L.-B.), Université Libre de Bruxelles, Brussels, 1070 Belgium
  • Sleep, Metabolism, and Health Center (L.L.M., E.T., R.L., E.V.C.), Department of Medicine, University of Chicago, Chicago, Illinois 60637
Corresponding author
Spiegel, K.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2014-08-01
Volume
99
Issue
8
Pages
2861-2868
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2013-4254
PMC
PMC4121029
OpenAlex
W2102478373
Cited by
127
References
46
Citations by year
2026: 7 · 2025: 11 · 2024: 10 · 2023: 7 · 2022: 12 · 2021: 12 · 2020: 9 · 2019: 12 · 2018: 5 · 2017: 8 · 2016: 16 · 2015: 14 · 2014: 4
FWCI
6.87
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • HAL (submittedVersion)
Funders
  • University of Chicago
  • National Institutes of Health (UL1TR000430)
  • National Institute on Aging (P01-AG11412., P01AG011412)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P60DK20595, P60DK020595)
  • National Center for Research Resources (P41RR013642)
  • NIH Clinical Center
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords
sleep restriction, sleep deprivation, hypothalamic-pituitary-adrenal axis, ACTH, cortisol, free cortisol, circadian rhythm, perceived stress, appetite, hunger, cardiometabolic risk, healthy men
MeSH terms
Adrenocorticotropic Hormone, Adult, Circadian Rhythm, Health, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Sleep, Sleep Deprivation, Time Factors, Cross-Over Studies, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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