Cortisol Response in Healthy and Diseased Dogs after Stimulation with a Depot Formulation of Synthetic ACTH (original) (raw)

Comparison of 2 Doses for ACTH Stimulation Testing in Dogs Suspected of or Treated for Hyperadrenocorticism

Journal of veterinary internal medicine, 2016

Lowering the cosyntropin dose needed for ACTH stimulation would make the test more economical. To compare the cortisol response to 1 and 5 μg/kg cosyntropin IV in dogs being screened for hyperadrenocorticism (HAC) and in dogs receiving trilostane or mitotane for pituitary-dependent HAC. Healthy dogs (n = 10); client-owned dogs suspected of having HAC (n = 39) or being treated for pituitary-dependent HAC with mitotane (n = 12) or trilostane (n = 15). In this prospective study, healthy dogs had consecutive ACTH stimulation tests to ensure 2 tests could be performed in sequence. For the first test, cosyntropin (1 μg/kg IV) was administered; the second test was initiated 4 hours after the start of the first (5 μg/kg cosyntropin IV). Dogs suspected of having HAC or being treated with mitotane were tested as the healthy dogs. Dogs receiving trilostane treatment were tested on consecutive days at the same time post pill using the low dose on day 1. In dogs being treated with mitotane or tr...

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.

Utility of 30 and 60 minute cortisol samples after high-dose synthetic ACTH-1-24 injection in the diagnosis of adrenal insufficiency

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...

Intramuscular administration of ACTH1-24 vs. 24-hour blood sampling in the assessment of adrenocortical function

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 ...

Comparison of salivary and calculated free cortisol levels during low and standard dose of ACTH stimulation tests in healthy volunteers

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.

Free and Total Plasma Cortisol Measured by Immunoassay and Mass Spectrometry Following ACTH 1–24 Stimulation in the Assessment of Pituitary Patients

The Journal of Clinical Endocrinology & Metabolism, 2013

Context: Measurement of plasma cortisol by immunoassay after ACTH 1-24 stimulation is used to assess the hypothalamic-pituitary-adrenal (HPA) axis. Liquid chromatography-tandem mass spectrometry (LCMS) has greater analytical specificity than immunoassay and equilibrium dialysis allows measurement of free plasma cortisol. Objective: We investigated the use of measuring total and free plasma cortisol by LCMS and total cortisol by immunoassay during an ACTH 1-24 stimulation test to define HPA status in pituitary patients. Design and Setting: This was a case control study conducted in a clinical research facility. Participants: We studied 60 controls and 21 patients with pituitary disease in whom HPA sufficiency (n ϭ 8) or deficiency (n ϭ 13) had been previously defined. Intervention: Participants underwent 1 g ACTH 1-24 intravenous and 250 g ACTH 1-24 intramuscular ACTH 1-24 stimulation tests. Main Outcome Measures: Concordance of ACTH 1-24-stimulated total and free plasma cortisol with previous HPA assessment. Results: Total cortisol was 12% lower when measured by immunoassay than by LCMS. Female sex and older age were positively correlated with ACTH 1-24-stimulated total and free cortisol, respectively. Measurements of total cortisol by immunoassay and LCMS and free cortisol 30 minutes after 1 g and 30 and 60 minutes after 250 g ACTH 1-24 were concordant with previous HPA axis assessment in most pituitary patients. However, free cortisol had greater separation from the diagnostic cutoff than total cortisol. Conclusions: Categorization of HPA status by immunoassay and LCMS after ACTH 1-24 stimulation was concordant with previous assessment in most pituitary patients. Free cortisol may have greater clinical use in patients near the diagnostic threshold.

Comparison of cortisol responses to low dose ACTH stimuli and injection stress

SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital

Comparison of cortisol responses to low dose ACTH stimuli and injection stress Objective: We performed a placebo-controlled, single-blind, pilot study to compare the efficacy and safety of low dose cosyntropin stimulation test with injection stress in the diagnosis of secondary adrenocortical insufficiency. Material and Methods: Twenty-five patients (22 F, 3 M) with a low or normal plasma ACTH level, morning plasma cortisol level <15 μg/dL and an indication of cosyntropin stimulation test for secondary adrenocortical insufficiency were included in the study. On the first day, the test was performed with direct intravenous injection with 1 mL 0.9% saline. On the second day at the same time and with the same method, the test was repeated with 1 μg/mL cosyntropin solution. Immediately prior to the procedure, blood samples were taken from the cannula located in the other forearm for measurement of plasma cortisol at 30 th and 60 th minutes. Results: The median ACTH value of the patients selected for the study was 22.10 pg/mL (14.00-29.30) and the mean plasma cortisol level was 6.71±2.00 μg/dL. The baseline plasma cortisol values measured at one minute in the placebo-controlled tests for comparison of injection stress with 1 μg cosyntropin stimulation were similar, but a significant statistically significant difference was found between plasma cortisol values measured at 30 th and 60 th minutes (p<0.001). Conclusion: Injection stress, which occurs during intravenous injection, does not cause an increase in cortisol responses. However, 1 μg cosyntropin stimulation test at the physiological doses produces a significant cortisol response, especially at 30 minutes.

Validation of a commercially available enzyme-linked immunosorbent assay (ELISA) for the determination of cortisol in canine plasma samples

Veterinary research communications, 1998

Samples were obtained from clinically normal dogs before and after ACTH stimulation and dexamethasone suppression tests. The test kit Enzymun-Test (Boehringer Mannheim) for determining cortisol concentrations in human plasma was used in connection with the analyser system Enzymun-Test (Boehringer Mannheim) System ES300 following the manufacturer's instructions. The intra-assay and inter-assay coefficients of variation were 1.28% and 5.64%, respectively. The mean recovery when assaying samples with a cortisol content of more than 100 nmol/L was 95.41%, but this percentage decreased in samples with lower cortisol levels. The sensitivity of the assay was 2.76 nmol/L. The results of the ACTH stimulation and dexamethasone suppression tests were similar to those published previously. The ELISA method evaluated allows a precise and sensitive determination of cortisol concentrations in canine plasma samples. The major drawback observed was the loss of accuracy at low cortisol concentrat...