Overnight ACTH-cortisol dose responsiveness: comparison with 24-h data, metyrapone administration and insulin-tolerance test in healthy adults (original) (raw)
Related papers
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.
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.
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 ...
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.
Endocrine, 2018
The ACTH1-24 stimulation test is commonly used to assess the hypothalamic-pituitary-adrenal (HPA) axis. Given variations in CBG concentration and binding affinity, serum total cortisol may misclassify some patients. Salivary cortisol correlates well with serum free cortisol but is easier to measure and widely available in commercial laboratories. The aim of this study was to investigate the utility of measuring salivary cortisol during the ACTH1-24 stimulation test. Case-control study in a clinical research facility. Eighty-seven patients with suspected cortisol deficiency, twenty-four healthy controls, and ten healthy women on the oral contraceptive (OC) underwent an intravenous 250 µg ACTH1-24 stimulation test. Concordance of ACTH1-24 stimulated serum and salivary cortisol was evaluated. There was a significant difference in serum cortisol between the healthy volunteers and the women on the OC (P < 0.001) but no difference in salivary cortisol. The lower limit of the reference ...
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 ...
Sex defines the age dependence of endogenous ACTH-cortisol dose responsiveness
American Journal of Physiology Regulatory Integrative and Comparative Physiology, 2009
Keenan DM, Roelfsema F, Carroll BJ, Iranmanesh A, Veldhuis JD. Sex define the age dependence of endogenous ACTH-cortisol dose responsiveness. Sex influences adrenal glucocorticoid responses to ACTH in experimental animals. Whether similar sex differences operate in humans is unknown. To test this notion, we estimated ACTH-cortisol dose-response properties analytically in 48 healthy adults (n ϭ 22 women, n ϭ 26 men), ages 18 -77 yr, body mass index (BMI) 18 -32 kg/m 2 , previously studied at two medical centers. Plasma ACTH and cortisol concentrations were measured every 10 min for 24 h. The 145 sample pairs were used in each subject to estimate ACTH-cortisol drive via a logistic function. Statistical analyses revealed that 24-h cortisol secretion (Ͼ82% pulsatile) fell in men (r ϭ Ϫ0.38, P ϭ 0.028) and rose in women (r ϭ ϩ0.37, P ϭ 0.045) with age (P ϭ 0.01 sex effect). The mechanisms involved decreased ACTH efficacy with age in men (r ϭ Ϫ0.35, P ϭ 0.04), and increased ACTH efficacy with age in women (r ϭ ϩ0.42, P ϭ 0.025) [P ϭ 0.009 sex effect]. ACTH potency diminished with higher BMI in men (r ϭ ϩ0.38, P ϭ 0.029) and in the cohort as a whole (r ϭ 0.34, P ϭ 0.0085). These outcomes demonstrate that sex, age, and BMI modulate selective properties of endogenous ACTHcortisol drive in humans, thereby indicating the need to control these three major variables in experimental comparisons.
Swiss medical weekly, 2014
In clinical practise the high dose ACTH stimulation test (HDT) is frequently used in the assessment of adrenal insufficiency (AI). However, there is uncertainty regarding optimal time-points and number of blood samplings. The present study compared the utility of a single cortisol value taken either 30 or 60 minutes after ACTH stimulation with the traditional interpretation of the HDT. Retrospective analysis of 73 HDT performed at a single tertiary endocrine centre. Serum cortisol was measured at baseline, 30 and 60 minutes after intravenous administration of 250 µg synthetic ACTH1-24. Adrenal insufficiency (AI) was defined as a stimulated cortisol level <550 nmol/l. There were twenty patients (27.4%) who showed an insufficient rise in serum cortisol using traditional HDT criteria and were diagnosed to suffer from AI. There were ten individuals who showed insufficient cortisol values after 30 minutes, rising to sufficient levels at 60 minutes. All patients revealing an insufficie...
Avaliação da função adrenal em cães portadores de doenças críticas com baixa dose de ACTH sintético
2020
A função do eixo hipotálamo-hipófise-adrenal pode estar comprometida em pacientes com doenças críticas, em especial casos de sepse, sendo nomeada de Insuficiência Corticosteroide Relacionada à Doença Crítica (ICRDC). O presente trabalho analisou a função do eixo hipotálamo-hipófise-adrenal em cães normais (n=10) e cães portadores de doenças críticas (n=16), por meio de determinações de ACTH (hormônio adrenocorticotrófico) endógeno, de cortisol basal e de cortisol após estímulo com baixa dose de ACTH sintético (1,0μg/kg/IV). Constatou-se que o teste de estimulação com ACTH na dose testada se mostrou eficaz para avaliação da função adrenal em cães sadios e doentes. Os cães doentes diferiram dos sadios ao apresentar valores maiores de cortisol basal. Oito cães doentes apresentaram diminuição do ACTH endógeno, do cortisol basal ou do Δ-cortisol. Não foram encontradas diferenças significativas entre os grupos Controle e Criticamente enfermos para o...