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 176 publications

(140 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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“…The proposed alterations include resistance to the negative feedback (impaired suppression) exerted by low oral dexamethasone or intravenous doses of glucocorticoids (17)(18)(19); elevated diurnal ACTH levels and altered pulsatile secretory ACTH dynamics (20), hyperesponsiveness to different peptides (CRH, AVP) (21), and increased cortisol production rate, as measured by stable isotope ratio (22).…”

Section: Obesity and Metabolic Syndromementioning

confidence: 99%

“…The increased HPA axis drive and production of cortisol observed in obese subjects is counterbalanced by enhanced urinary excretion rate of free cortisol and its metabolites and also by its enhanced peripheral clearance (21)(22)(23), resulting in normal (or even low) blood levels (figure 2). This has been recently explained by observations that there is a tissue-specific deregulation of cortisol metabolism in human obesity in which 11βHSD1 activity is upregulated in adipose tissue and underegulated in the liver, resulting in lower plasma cortisol levels with a compensatory rise in ACTH and cortisol production (see below).…”

Section: Obesity and Metabolic Syndromementioning

confidence: 99%

Adipose tissue expression of 11beta-Hydroxysteroid dehydrogenase type 1 in cushing's syndrome and in obesity

Espíndola-Antunes

Kater

2007

Arq Bras Endocrinol Metab

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Glucocorticoids have a major role in determining adipose tissue metabolism and distribution. 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) is a NADPHdependent enzyme highly expressed in the liver and adipose tissue. In most intact cells and tissues it functions as a reductase (to convert inactive cortisone to active cortisol). It has been hypothesized that tissue-specific deregulation of cortisol metabolism may be involved in the complex pathophysiology of the metabolic syndrome (MS) and obesity. Transgenic mice overexpressing 11βHSD1 in adipose tissue develop obesity with all features of the MS, whereas 11βHSD1-knockout mice are protected from both. The bulk of evidences points to an overexpression and increased activity of 11βHSD1 also in human adipose tissue. However, 11βHSD1 seems to adjust local cortisol concentrations independently of its plasma levels. In Cushing's syndrome, 11βHSD1 is downregulated and may not be responsible for the abdominal fat depots; it also undergoes downregulation in response to weight loss in human obesity. The nonselective 11βHSD1 inhibitor carbenoxolone improves insulin sensitivity in humans, and selective inhibitors enhance insulin action in diabetic mice liver, thereby lowering blood glucose. Thus, 11βHSD1 is now emerging as a modulator of energy partitioning and a promising pharmacological target to treat the MS and diabetes. Os glicocorticóides (GC) têm papel importante na determinação do metabolismo e da distribuição do tecido adiposo. A 11β-hidroxisteróide desidrogenase tipo 1 (11βHSD1) é uma enzima dependente de NADPH, altamente expressa nos tecidos hepático e adiposo. Em muitas células e tecidos intactos, ela funciona como redutase (convertendo cortisona em cortisol). Postula-se que uma desregulação tecido-específica do cortisol estaria envolvida na complexa fisiopatologia da síndrome metabólica (SM) e obesidade. Ratos que superexpressam 11βHSD1 no tecido adiposo desenvolvem obesidade e todas as características da SM, enquanto ratos knockout para 11βHSD1 são protegidos. Evidências apontam para uma super-expressão e aumento da atividade 11βHSD1 também no tecido adiposo humano. Entretanto, a 11βHSD1 parece ajustar a concentração local de cortisol independente da sua concentração séri-ca. Na síndrome de Cushing, a expressão da 11βHSD1 é regulada para baixo, não devendo ser a causa dos depósitos de gordura visceral; em obesos, há também regulação para baixo em resposta à perda de peso. A carbenoxolona, um inibidor não seletivo da 11βHSD1, melhora a sensibilidade insulínica em humanos e inibidores seletivos aumentam a sensibilidade insulínica hepática e melhoram o controle glicêmico em ratos diabéticos. Assim, a 11βHSD1 está emergindo como um modulador da compartimentalização de energia e um alvo farmacológico promissor para o tratamento da SM e do diabetes.

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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 176 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

Adipose tissue expression of 11beta-Hydroxysteroid dehydrogenase type 1 in cushing's syndrome and in obesity

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