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Direct measurement of the nonapeptide vasopressin has been limited by analyte instability ex vivo and in vivo rapid degradation, low serum concentrations requiring a sensitive assay and inherent secretory pulsatility. Copeptin is a 39 amino acid glycopeptide cleavage product of vasopressin synthesis with high stability, providing a marker of vasopressin secretion. Copeptin measurement has applications in diagnosis of diabetes insipidus and other diseases with altered vasopressin secretion. This review summarises our current understanding of serum copeptin measurement in diabetes insipidus and possible future applications of copeptin assays. As vasopressin is a stress hormone, there is emerging evidence on the use of copeptin for diagnosis and prognostication of disorders such as syndrome of inappropriate anti-diuretic hormone secretion, diabetes mellitus, critical illness, stroke, cardiovascular disease, respiratory disease, renal disease and thermal stress. Copeptin concentration measurement is likely to improve the diagnostic reliability of diabetes insipidus and, as a marker of stress, may have diagnostic or prognostic utility in specific clinical circumstances. Further studies are needed to determine if goal-directed therapy using plasma copeptin concentrations may improve patient outcomes. [ABSTRACT FROM AUTHOR]

Corticosteroid-binding globulin (CBG) is involved in the regulation of cortisol delivery. Neutrophil elastase-mediated cleavage of high to low affinity CBG (haCBG to laCBG) induces cortisol release at inflammatory sites. Past studies have shown reduced CBG in obesity, an inflammatory state, particularly in central adiposity/metabolic syndrome. We performed an observational, crosssectional study of the effects of obesity, age and sex on ha/laCBG in 100 healthy volunteers. Total and haCBG levels were 11 % higher in women but did not vary with age or menopausal status. Total CBG levels were lower with increased body weight and waist circumference; laCBG levels were lower with increased body weight, waist circumference, body mass index and body fat; higher haCBG levels were seen with increased body fat. The relation between CBG and adiposity appeared to be driven predominantly by the metabolic syndrome group. The results suggest reduced CBG cleavage in central obesity, possibly contributing to the characteristic inflammatory phenotype of the central obesity and metabolic syndrome. The mechanism of gender differences in CBG levels is unclear [ABSTRACT FROM AUTHOR]

Corticosteroid-binding globulin (CBG, transcortin) is the primary cortisol binding protein. It is a non-inhibitory serine protease inhibitor, capable of conformational change from a high cortisol-binding affinity form to a low affinity form upon cleavage of its reactive centre loop by various proteases, such as neutrophil elastase. The burgeoning inflammatory role of CBG applies to acute, severe inflammation where depletion is associated with mortality, and to chronic inflammation where defects in cortisol delivery may perpetuate inflammation. Naturally occurring human mutations influence a wide range of CBG properties and point toward a role in hitherto unexplained chronic musculoskeletal pain and fatigue disorders as well as potentially affecting fertility outcomes including offspring gender. In vitro and knock-out animal models of CBG propose a role for CBG in cortisol transport to the brain, providing a foundation for understanding the human observations in those with CBG mutations and sex differences in stress-related mood and behaviour. Finally, CBG measurement has a practical role in the estimation of free cortisol, useful in clinical circumstances where CBG levels or cortisol binding affinity is reduced. Taken together, novel data suggest a role for cortisol in targeted cortisol delivery, with implications in acute and chronic inflammation, as well as roles in metabolism and neurocognitive function, implying that CBG is a multifaceted component in the mechanisms of hypothalamic-pituitary-adrenal axis related homeostasis. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the incidence of adrenal crises (AC) and the prescription of short-acting glucocorticoids (GC) in different geographic areas. To do this we conducted a descriptive study of AC hospitalisations and prescriptions for two GCs (hydrocortisone (HC) and cortisone acetate (CA)), and fludrocortisone acetate (FA), in different geographic areas of Australia between 1999/2000 and 2011/2012, using government databases. There were 2 584 hospital admissions for AC in Australia between 1999/00 and 2011/12 and the corresponding admission rates increased significantly from 7.4 to 11.1/106/year (p < 0.001). AC admission rates increased in 5 out of 6 geographic areas. Prescription rates for the combined GCs (HC/CA) increased at an annual rate of between 0.2-2.0 % in all areas. All areas had significant (p < 0.01) increases in HC prescription rates (4.5 % to 13.7 % annually) and CA prescription rates decreased in 5 out of the 6 regions (3.5 % annual decrease to a 0.5 % annual increase). When the geographic areas were combined, there was a significant correlation between the AC admission rates and HC/CA prescription rates (r = 0.30, p < 0.01). Admissions for AC and GC prescriptions increased significantly in Australia after 1999 and these varied significantly by geographic area. These results suggest that modern recommendations for lower dose, short-acting GC replacement may be of concern and further investigation is warranted. [ABSTRACT FROM AUTHOR]

Morbidity from adrenal insufficiency (AI) in Australia is poorly described. The objective of this study was to evaluate AI morbidity patterns in adults between 1999/2000 and 2011/2012 using national databases. A descriptive study of hospitalisations for AI and adrenal crises (AC) in adults and trends in prescriptions for 2 short-acting glucocorticoids (GC) was designed. The setting was the Australian healthcare system. Main outcome measures are the trends in hospitalisation and prescription rates. There were 7 378 hospital admissions for treatment of AI in adults between 1999/00 and 2011/12. Of these, 29.5 % were for an AC. Admission rates for AC increased from 9.5 to 12.4 admissions/106/year (p < 0.05). There was a 5.8 % decrease in admission rates for AI (excluding AC), from 27.0 to 25.5/106/year (p = ns). Shortacting GC [hydrocortisone (HCT) and cortisone acetate (CA)] prescription rates increased significantly (p < 0.001) from 3 176.1/106 to 3 463.8/106. Prescription rates for CA decreased by 22.4 % (p < 0.001) but HCT prescription rates increased to 77.1 % (p < 0.001). The increase in AC admission rates was positively correlated with the rise in both the total GC prescription rate (r = 0.63, p < 0.05) and the HCT prescription rate (r = 0.74, p < 0.01). Over the 13-year study period, there was a 30.8 % increase in hospitalisation rates for ACs and a concomitant 77.1 % increase in prescribing of HCT. The association between AC events and HCT use and/or reduced effective GC dose is plausibly causal, but confirmatory studies are required before suggesting any change to GC replacement in AI. [ABSTRACT FROM AUTHOR]

Islet cell transplantation has emerged as a treatment modality for type 1 diabetes in the last 15 years due to the Edmonton protocol leading to consistent and sustained exogenous insulin independence post-transplantation. In recent years, consortia that involve both local and remote islet cell centers have been established, with local centers responsible for processing and shipping of islet cells, and remote centers only transplanting them. There are, however, few data on patient outcomes at remote centers. A tendency for high fasting glucose despite insulin independence was noted by us and others with an unknown mechanism. This review provides a brief history of islet cell transplantation, and focuses on the South Australian remote center experience: the challenges, screening criteria, and the impact on incretin hormone secretion of insulin independent transplant patients. [ABSTRACT FROM AUTHOR]

Leptin, produced by adipocytes, has homeostatic effects on body fat mass through inhibition of appetite and stimulation of the sympathetic nervous system. Several studies have reported that high-dose exogenous glucocorticoids increase circulating leptin concentrations in humans. Conversely, leptin has inhibitory effects on the hypothalamic-pituitary-adrenal (HPA) axis, both at the hypothalamic and adrenal levels. We hypothesized that acute hypercortisolism, in the physiological range, may not alter leptin secretion. Four stimuli of the HPA axis were administered to eight healthy male volunteers in a placebo-controlled study. On separate afternoons, in a randomised order, fasting subjects received i.v. injections of saline, naloxone (125 μg/kg); vasopressin (0.0143 IU/kg); naloxone and vasopressin in combination; or insulin (0.15 U/kg; a dose sufficient to induce hypoglycaemia). Plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol and leptin were measured before and for 120 min after the injection. The cortisol secretory response was greatest after insulin-hypoglycaemia, this response was significantly greater than that following naloxone, naloxone/vasopressin, or vasopressin alone. Despite the cortisol release, leptin concentrations were not increased after any stimulus. Insulin-hypoglycaemia was associated with a decrease in leptin concentration at 60 and 90 min, while naloxone did not alter leptin concentrations. However, basal leptin concentrations were positively correlated with integrated ACTH and cortisol responses to naloxone, but did not correlate with ACTH or cortisol responses to the other stimuli. Thus acute elevations of plasma cortisol, in the physiological range, do not appear to influence plasma leptin concentrations. The fall in plasma leptin concentration after insulin-induced hypoglycaemia may reflect catecholamine secretion after this stimulus. [ABSTRACT FROM AUTHOR]

The hypothalamic-pituitary-adrenal axis exerts profound, multilevel inhibitory effects on the female reproductive system. Corticotropin-releasing hormone (CRH) and CRH-induced proopiomelanocortin peptides inhibit hypothalamic gonadotropin-releasing hormone secretion, whereas glucocorticoids suppress pituitary luteinizing hormone and ovarian estrogen and progesterone secretion and render target tissues resistant to estradiol. The hypothalamic-pituitary-adrenal axis is thus responsible for the "hypothalamic" amenorrhea of stress, which is also seen in melancholic depression, malnutrition, eating disorders, chronic active alcoholism, chronic excessive exercise, and the hypogonadism of the Cushing syndrome. Conversely, estrogen directly stimulates the CRH gene promoter and the central noradrenergic system, which may explain adult women's slight hypercortisolism; preponderance of affective, anxiety, and eating disorders; and mood cycles and vulnerability to autoimmune and inflammatory disease, both of which follow estradiol fluctuations. Several components of the hypothalamic-pituitary-adrenal axis and their receptors are present in reproductive tissues as autacoid regulators. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary (ovulation and luteolysis) and endometrium (blastocyst implantation and menstruation), and placental CRH, which may participate in the physiology of pregnancy and the timing of labor and delivery. The hypercortisolism of the latter half of pregnancy can be explained by high levels of placental CRH in plasma. This hypercortisolism causes a transient postpartum adrenal suppression that, together with estrogen withdrawal, may partly explain the depression and autoimmune phenomena of the postpartum period. [ABSTRACT FROM AUTHOR]