Table 1

Previous publications on cortisol concentrations and circadian rhythm in neonates infants and children36 69–82

StudyAge rangeNumber of subjects24 hours profileNotesStudy findingsStudy conclusions
Neonatal studies
Price et al69Neonates8 termYes: 4 samplesSalivary sampling longitudinal study term till 24 weeks ageVariable cortisol pattern until average of 12 weeksCircadian rhythm established in first few months of life
Hindmarsh et al70Neonates and adults10 term
10 preterm
10 adults
Yes: 930 and 1530 samplesVenous samplingMorning cortisol was significantly higher than afternoon in all groupsDiurnal rhythm seen in neonates aged 3–4 days
Jonetz-Mentzel and Wiedemann71Neonates–18 years687 healthy childrenNo: one sample 08:00–10:00 hoursVenousCortisol in neonates aged 5 days lower than other age groupsLow cortisol in neonates aged 5 days reflects lack of circadian rhythm
Santiago et al72Neonates9 termYesThree salivary samples per day collected on weeks 2, 4, 8, 12, 16, 20, 24Circadian rhythm appeared at median 8 weeks
No relationship to sleeping through the night
Circadian rhythm in cortisol appears earlier than previously expected and as early as 2 weeks in some babies
Iwata et al73Neonates27 termYesEight salivary samples over a 24-hour periodNon-circadian rhythm
Acrophase of cortisol secretion linked to birth time in infants <5 days of age
Initial HPA axis activity entrained to birth time rather than day/night periodicity
Stroud et al74Neonates100 termNoLongitudinal salivary testing in cohort with/without maternal smoking for 1 monthCortisol higher in maternal smoking neonatesMaternal smoking alters HPA axis in neonates: epigenetic alteration of glucocorticoid receptor postulated
Studies in older children
Lashansky et al752 months–17 years102 termNo: Synacthen testCross-sectional Synacthen-stimulated levelsStandard Synacthen test demonstrated rapid cortisol responseCortisol response highest in infants and postpubertal
de Weerth et al762–5 months14 termYes5×salivary monthlyCircadian patterns depended significantly on analysisCircadian rhythm can be seen from 2 months onwards
Wallace et al77Median age 11 years14 healthyYesSerum samples every 20 min for 24 hoursClear circadian rhythm demonstrated for cortisol and ACTH
No relationship to puberty or sex
Normal circadian rhythm is seen in children with similar levels of cortisol secretion to adults
Ghizzoni et al786–11 years8 healthy
8 NCCAH
YesComparison of cortisol and TSH curves24-hour cortisol AUC not different but NCCAH had lower nocturnal cortisol and higher nocturnal TSHTSH and cortisol inversely correlated. Blunted overnight cortisol rise in NCCAH leads to higher TSH
Knutsson et al792–18 years235 healthy childrenYesVenous cross-sectional with longitudinal n=28No differences between males or females or age groups or pubertal status in circadian rhythm and cortisolCircadian rhythm and absolute cortisol does not vary through childhood or puberty
DeVile et al803–20 years50 SAIYesVenousPatients had a non-physiological mid-morning nadirThrice-daily hydrocortisone did not adequately replicate the circadian rhythm of cortisol in patients
Hermida et al81Prepubertal children135 children:
14 GHD
36 SS
57 VSS
28 NS
YesSerum cortisol and GH analysisSimilar circadian rhythm for cortisol secretion seen in all groupsThe relationship between GH and cortisol secretion is unclear, and GH-deficient children can have entirely normal cortisol secretion patterns
Peters et al365–9 years and adults29 SS
80 adults
YesSerum cortisol profiles
Deconvolution analysis
Circadian pattern similar in adults and children with earlier nadir and slightly higher peaks in children
Mean 24-hour cortisol secretion
Adults 6.3 mg/m2/day
Children 8.0 mg/m2/day
Non-significant difference
Morning cortisol is a fair reflection of adrenal sufficiency in adults and children, but care must be taken when assessing nadir in children (ie, for Cushing’s disease)
Shirtcliff et al829–15 years306 children followed longitudinallyYes: 3 samplesSalivary cortisol followed longitudinallyStable intra-individual circadian rhythm
Sex differences seen at puberty
Circadian rhythm is strongly individual and stable across pubertal development
  • ACTH, adrenocorticotrophic hormone; AUC, area under the curve; GHD, growth hormone deficiency; HPA, hypothalamic-pituitary-adrenal; NCCAH, non-classical congenital adrenal hyperplasia; NS, normal stature; SAI, secondary adrenal insufficiency; SS, idiopathic short stature; TSH, thyroid-stimulating hormone; VSS, very short stature <−3SDS.