Association of 24-Hour Cortisol Production Rates, Cortisol-Binding Globulin, and Plasma-Free Cortisol Levels with Body Composition, Leptin Levels, and Aging in Adult Men and Women

Purnell, Jonathan Q.; Brandon, David D.; Isabelle, Lorne M.; Loriaux, D. Lynn; Samuels, Mary H.

doi:10.1210/jc.2003-030440

Cited by 171 publications

(127 citation statements)

References 51 publications

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“…With respect to BMI, cortisol production rate increases with increasing BMI, as does cortisol clearance. In addition, corticosteroid-binding globulin levels are lower; however, this does not always appear to manifest as increased free cortisol levels (33). Consequently, there was no difference in peak cortisol responses in subjects with a BMI SDS O85th centile within our cohort.…”

Section: Discussionmentioning

confidence: 60%

Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children

O’Grady

Hensey

Fallon

et al. 2013

European Journal of Endocrinology

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Objective: Based on adult data, a peak cortisol response R500 nmol/l to insulin-induced hypoglycaemia constitutes a normal. Age-specific reference ranges for basal morning cortisol have been developed for clinical use in the paediatric population. Such reference ranges are not clearly established for peak cortisol responses to insulin-induced hypoglycaemia despite limited data suggesting an effect of age on peak cortisol. The aims of this study were to assess factors affecting the cortisol response to insulin-induced hypoglycaemia in children and to determine whether the peak cortisol response was related to age. Design: The present study was a retrospective cohort study. Methods: Retrospective analysis of children and adolescents aged %18 years undergoing the insulin tolerance test with adequate hypoglycaemia was undertaken. Patients with hypopituitarism or severe hypothalamic-pituitary-adrenal axis impairment (peak cortisol value !400 nmol/l) or using systemic glucocorticoids were excluded. Results: Two hundred and twenty-three tests were analysed. Peak cortisol responses R500 nmol/l occurred in 183 (82%) tests. Age was negatively associated with peak cortisol responses (rZK0.15, PZ0.03). A peak cortisol response !500 nmol/l was significantly less common in patients aged !12 years (9/97 (9%) vs 31/126 (25%); PZ0.004). In children aged !12 years, the median (5th-95th centiles) peak cortisol values were 610 (480-806) nmol/l compared with 574 (442-789) nmol/l in children aged R12 years (P!0.004). Similarly, median cortisol increment was significantly higher in younger patients (301 nmol/l compared with 226 nmol/l (PZ0.0004)). Conclusions: Use of a single peak cortisol threshold in children of all ages is not appropriate and will result in overdiagnosis of adrenal insufficiency in adolescents.

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Section: Discussionmentioning

confidence: 60%

Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children

O’Grady

Hensey

Fallon

et al. 2013

European Journal of Endocrinology

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“…Moreover, a well-defined 24-h plasma cortisol rhythm is clearly evident well into old age (Figs. 1c, g;Wise 1999;Purnell et al 2004;Urbanski et al 2004;Downs et al 2008). Although the functional significance of all these age-related hormonal changes is unclear, a significant elevation of the cortisol baseline means that the brain and peripheral organs, such as the liver, will receive little or no daily respite from the influence of cortisol, which may predispose the elderly to insomnia as well as to metabolic disorders (Scheer et al 2009).…”

Section: Age-related Endocrine Changesmentioning

confidence: 99%

Age-related changes in neuroendocrine rhythmic function in the rhesus macaque

Urbanski

Sorwell

2011

AGE

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Many environmental conditions show rhythmic changes across the 24-h day; these include changes in light intensity, ambient temperature, food availability, and presence or absence of predators. Consequently, many organisms have developed corresponding adaptations, which ensure that specific physiological and behavioral events occur at an appropriate time of the day. In mammals, the underlying mechanism responsible for synchronizing internal biochemical processes with circadian environmental cues has been well studied and is thought to comprise three major components: (1) photoreception by the retina and transmission of neural signals along the retinohypothalamic tract, (2) integration of photoperiodic information with an internal reference circadian pacemaker located in the suprachiasmatic nucleus, and (3) dissemination of circadian information to target organs, via the autonomic nervous system and through humoral pathways. Given the importance that neuroendocrine rhythms play in coordinating normal circadian physiology and behavior, it is plausible that their perturbation during aging contributes to the etiology of age-related pathologies. This mini-review highlights some of the most dramatic rhythmic neuroendocrine changes that occur in primates during aging, focusing primarily on data from the male rhesus macaques (Macaca mulatta). In addition to the ageassociated attenuation of hormone levels and reduction of humoral circadian signaling, there are also significant age-related changes in intracrine processing enzymes and hormone receptors which may further affect the functional efficacy of these hormones. Rhesus macaques, like humans, are large diurnal primates and show many of the same physiological and behavioral circadian changes during aging. Consequently, they represent an ideal translational animal model in which to study the causes and consequences of age-associated internal circadian disruption and in which to evaluate novel therapies.

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“…Although many obese individuals resemble patients with excess cortisol exposure, plasma cortisol levels in overweight and obese subjects have been found to be either similar to or lower than those in non-obese individuals, suggesting that cortisol metabolism may be altered in some overweight or obese individuals [1][2][3]. Indeed, there are differences in cortisol metabolism between obese men and women [4] according to patterns of regional body fat distribution [5].…”

Section: Introductionmentioning

confidence: 99%

Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men

et al. 2007

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Aims/hypothesis The regulation of cortisol metabolism in vivo is not well understood. We evaluated the relationship between cortisol metabolism and insulin sensitivity, adjusting for total and regional fat content and for non-alcoholic fatty liver disease. Materials and methods Twenty-nine middle-aged healthy men with a wide range of BMI were recruited. We measured fat content by dual-energy X-ray absorptiometry and magnetic resonance imaging (MRI), liver fat by ultrasound and MRI, the hypothalamic-pituitary-adrenal axis by adrenal response to ACTH 1-24 , unconjugated urinary cortisol excretion, corticosteroid-binding globulin, and cortisol clearance by MS. We assessed insulin sensitivity by hyperinsulinaemic-euglycaemic clamp and by OGTT. Results Cortisol clearance was strongly inversely correlated with insulin sensitivity (M value) (r=−0.61, p=0.002). Cortisol clearance was increased in people with fatty liver compared with those without (mean±SD: 243±10 vs 158± 36 ml/min; p = 0.014). Multiple regression modelling showed that the relationship between cortisol clearance and insulin sensitivity was independent of body fat. The relationship between fatty liver and insulin sensitivity was significantly influenced by body fat and cortisol clearance. Conclusions/interpretation Cortisol clearance is strongly associated with insulin sensitivity, independently of the amount of body fat. The relationship between fatty liver and insulin sensitivity is mediated in part by both fatness and cortisol clearance.

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Association of 24-Hour Cortisol Production Rates, Cortisol-Binding Globulin, and Plasma-Free Cortisol Levels with Body Composition, Leptin Levels, and Aging in Adult Men and Women

Cited by 171 publications

References 51 publications

Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children

Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children

Age-related changes in neuroendocrine rhythmic function in the rhesus macaque

Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men

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