Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans (original) (raw)
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Serum free cortisol as an ancillary tool in the interpretation of the low-dose 1-μg ACTH test
Clinical Endocrinology, 2011
Objective: Serum free cortisol, rather than serum total cortisol determines glucocorticoid activity in vivo, but how the considerable inter-subject variation in ambient serum free cortisol affects the outcome of dynamic hypothalamic-pituitaryadrenal (HPA) assessment in non-critically ill subjects is unknown. Design, Patients and Measurements: We performed the low dose 1µg ACTH test in 75 subjects referred for HPA evaluation. Serum total cortisol was determined by a chemiluminescence method, and serum free cortisol was measured by the same method following equilibrium dialysis. In a subset of these patients, salivary cortisol was also measured. Results: Mean fraction of free cortisol was 5.07±4.08% (± SD; range 1.77-10.1%). Although no correlation was seen between total cortisol and the fraction (%) of free serum cortisol, a positive correlation existed between baseline total and free cortisol (R=0.539 P=0.01), as well as between peak ACTH-stimulated total and free cortisol (R=0.619; P=0.01). There was no correlation between baseline salivary cortisol and serum free cortisol and between peak ACTH-stimulated salivary and serum free cortisol .Using the lowest attained peak serum free cortisol in subjects whose total cortisol response to ACTH was normal (≥500nmol/l), the minimal "pass" level for normal serum free cortisol response to 1 µg ACTH was set at 24.84 nmol/l. Five of the 19 subjects showing subnormal total cortisol response to1 µg ACTH had normal serum free cortisol response. Conclusions:Discrepancies between the peak free and total cortisol were noted mostly for subjects whose ACTH-stimulated total cortisol peaked between 440-580nmol/l. At this ranges, the measurement of serum free cortisol allows further refinement of the assessment of borderline responses to 1μg ACTH.
Annals of The New York Academy of Sciences, 2002
Abstract: Evidence from experimental animal studies show that sex hormones influence the glucocorticoid response to a variety of inflammatory and noninflammatory stimuli. In this study we assessed gender differences in the response of ACTH and cortisol in normal young male and female humans following intravenous infusion of human IL-6 in various dosages. Males presented a significantly stronger ACTH production in response to IL-6 than females. Peak cortisol response, however, was similar in males and females. Cortisol/ACTH ratios were significantly higher in females than in males, both at baseline and after each of the IL-6 dosages. These results suggest that an effective glucocorticoid response requires similar levels of IL-6 in males and females. However, they also suggest that the adrenals of males and females have different sensitivities to ACTH (higher in females) and possibly also to direct IL-6 stimulation.
European Journal of Endocrinology, 1999
To analyse further the ACTH(1-24) low-dose test, which is of clinical interest, we have examined the dose-response relationship between plasma ACTH(1-24) and cortisol concentrations after i.v. administration of increasing doses (1, 5 or 250 mg) of ACTH(1-24) as a bolus. In addition, we have measured plasma ACTH(1-39) and cortisol levels after an insulin tolerance test (ITT). Although there was a dose-response relationship between plasma ACTH(1-24) immunoreactivity and the dose injected, cortisol peaks were comparable, but lower than those reached after an ITT. Under these experimental conditions, an increase in plasma ACTH as low as 13 pmol/l (i.e. the increase obtained with the 1 mg dose) induced a near maximal cortisol response. Following injection of 1 mg ACTH(1-24), peak ACTH values were short lasting, similar to physiological daily bursts. After injection of 5 mg ACTH(1-24), plasma ACTH concentrations were higher than those reached during an ITT, but clearly shorter lasting. Injection of 250 mg ACTH(1-24) induced strikingly supraphysiological levels of plasma ACTH. We conclude that neither regular nor low-dose ACTH tests can fully reproduce the ITT. Our observations strongly suggest that the low-dose ACTH(1-24) test (1 mg) can be useful to estimate the adrenal sensitivity under basal, physiological conditions.
Endocrine, 2014
Salivary cortisol (SC) has been increasingly used as a surrogate biomarker of free cortisol (FC) for the assessment of hypothalamo-pituitary-adrenal (HPA) axis, but there are not enough data regarding its use during ACTH stimulation tests. Therefore, we aimed to determine the responses of SC, calculated free cortisol (cFC) and free cortisol index (FCI) to ACTH stimulation tests in healthy adults. Forty-four healthy volunteers (24 men and 20 women) were included in the study. Low-dose (1 lg) and standard-dose (250 lg) ACTH stimulation tests were performed on two consecutive days. Basal and stimulated total cortisol (TC) and cortisol-binding globulin (CBG) levels and SC levels were measured during both doses of ACTH stimulation tests. cFC (by Coolens' equation) and FCI levels were calculated from simultaneously measured TC and CBG levels. The minimum SC, cFC, FCI levels after low-dose ACTH stimulation test were 0.21, 0.33, 16.06 lg/dL, and after standard-dose ACTH were 0.85, 0.46, 26.11 lg/dL, respectively, in healthy individuals who all had TC responses higher than 20 lg/dL. Peak CBG levels after both doses of ACTH stimulation tests were found to be higher in women than in men. So, by its effect, peak cFC and FCI levels were found to be lower in female than in male group. Neither TC nor SC levels were affected by gender. cFC and FCI levels depend on CBG levels and they are affected by gender. Cutoff levels for SC, cFC, FCI levels after both low-and standard-dose ACTH stimulation are presented. Studies including patients with adrenal insufficiency would be helpful to see the diagnostic value of these suggested cutoff levels.
Hormones (Athens, Greece)
The standard intravenous short Synacthen test (SSST) has long been accepted as one of the most reliable diagnostic tests of adrenocortical insufficiency. Intramuscular (i.m.) administration of ACTH obviates the need of venous cannulation and can be used as an alternative to the intravenous test. Nevertheless, reports of correlation between cortisol response to i.m. ACTH1-24 and 24-hr average cortisol concentration are scarce. We studied this relation in 64 nonobese healthy men. Blood samples for serial cortisol measurements were collected hourly over 24 hrs. The following day, blood samples were collected at baseline and at 30 and 60 min after intramuscular (i.m.) administration of 250 microg of ACTH1-24. All healthy men reached 24-hr serum cortisol peak values (Cmax) between 0600 h and 1000 h. Following i.m. ACTH1-24, cortisol levels significantly increased at both 30 (C30ACTH) and 60 (C60ACTH) minutes, when compared to baseline values. C30ACTH and C60ACTH significantly correlated ...
Pituitary, 2010
Evaluation of the HPA axis is still a challenge; due to different sensitivities and stimulation efficiencies of dynamic tests, lack of standard assays for cortisol measurement and lack of data regarding the effects of age and gender on the results of the HPA axis evaluation with different dynamic tests. This study was performed to compare 1 lg ACTH, 250 lg ACTH and glucagon tests in the evaluation of HPA axis. The study was carried out on 55 healthy individuals (28 men, 27 women). 10-12 volunteers were included from every decades between 20 and 70 years. Low dose short synacthen test (1 lg ACTH), standard dose short synacthen test (250 lg ACTH) and glucagon tests were performed consecutively. The mean peak cortisol response to standard dose ACTH stimulation test was found to be significantly higher than the low dose ACTH and glucagon stimulation tests. The mean peak cortisol responses to low dose ACTH and the glucagon stimulation tests were not significantly different. The mean peak cortisol responses did not differ significantly between different age or sex groups. The lowest peak cortisol responses obtained after low dose ACTH and glucagon stimulation tests were 12.5 and 9.1 lg/dl respectively in the volunteers who all had cortisol responses higher than 20 lg/dl after standard dose ACTH stimulation test. The lowest cortisol responses obtained during 250 lg ACTH, 1 lg ACTH and glucagon stimulation tests were found to be 20.1, 12.5 and 9.1 lg/dl in a known group of healthy people. So the consideration of appropriate hormonal cutoff levels for each test seems reasonable. The age, sex and body mass indeces were not shown to affect the cortisol response to dynamic stimulation tests.
Journal of Medical Biochemistry, 2016
Summary Background: Systemic inflammatory response syndrome (SIRS) changes cortisol dynamics and indicates dissociation between the adrenal cortex and the hypothalamo-pituitary unit. The aim of this study was to assess the cortisol response after stimulation with ACTH1-24 in patients with SIRS at admission to the Respiratory Intensive Care Unit (RICU) and seven days later. Methods: Fifty-four subjects were included in the study, and SIRS was defined according to the Consensus Conference criteria from 1992. Severity of the disease was determined using the APACHE II score, and organ dysfunction using the SOFA score. Low-dose (1 μg) ACTH test (LDT) was performed in all patients, and cortisol was determined along with basal ACTH. Data were analyzed using parametric and nonparametric tests and regression analysis. The results are presented as mean ± standard deviation, and P<0.05 was considered statistically significant. Results: There were no differences in cortisol values between th...
Salivary cortisol in low dose (1 µg) ACTH test in healthy women: comparison with serum cortisol
Physiological Research, 2007
To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 microg has become preferred as a more physiological stimulus than the commonly used 250 microg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 microg ACTH stimulation. This approach was compared with the common method based on the changes of total serum cortisol. Intravenous, low-dose ACTH test was performed in 15 healthy women (aged 22-40 years) with normal body weight, not using hormonal contraceptives, in the follicular phase of the menstrual cycle. Blood and saliva for determination of cortisol were collected before ACTH administration and 30 and 60 min after ACTH administration. Basal concentration of salivary cortisol (mean +/- S.E.M., 15.9+/-1.96 nmol/l) increased after 1 microg ACTH to 29.1+/-2.01 nmol/l after 30 min, and to 27.4+/-2.15 nmol/l after 60 min. The differences between ...
Psychosomatics, 2003
A reduced secretion of cortisol has been proposed as a possible explanation of the symptoms in chronic fatigue syndrome. However, the evidence of hypocortisolism in chronic fatigue syndrome is conflicting. In order to simultaneously assess possible alterations in adrenocortical sensitivity and secretory adrenal reserve, the authors administered both low-dose and high-dose ACTH to a group of 18 chronic fatigue syndrome patients and 18 age-and gender-matched healthy comparison subjects. No response differences for salivary and plasma cortisol were detectable after administration of either low-dose or high-dose ACTH, indicating that primary adrenal insufficiency is unlikely to play a significant role in the etiology of chronic fatigue syndrome.