Ignite Creation Date:
2024-05-05 @ 9:16 PM
Last Modification Date:
2024-10-26 @ 10:02 AM
Study NCT ID:
NCT00851942
Status:
COMPLETED
Last Update Posted:
2020-08-12
First Post:
2009-02-25
Brief Title:
Determination of Method-specific Normal Cortisol and Adrenal Hormone Responses to the Short Synacthen Test
Sponsor:
Cardiff University
Organization:
Cardiff University
Study Overview
Official Title:
Determination of Method-specific Normal Cortisol and Adrenal Hormone Responses to the Short Synacthen Test
Status:
COMPLETED
Status Verified Date:
2020-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Objectives
To establish valid serum total cortisol and salivary cut-offs for use with the short Synacthen test in patients with normal CBG concentrations
To investigate using current assays the effect of assay differences on the serum total cortisol cut-off
To explore the performance of these cut-offs in groups of patients with suspected adrenal insufficiency and high and low serum CBG concentration
Methodology An ACTH test 250 micrograms iv ACTH1-24 will be undertaken in healthy volunteers women taking an oestrogen-containing oral contraceptive pill OCP patients with adrenal insufficiency and patients with low serum albumin Serum cortisol in the samples collected from healthy volunteers will be measured using GC-MS Advia Centaur Siemens Architect Abbott Modular Analytics E170 Roche Immulite 2000 Siemens and Access Beckman automated immunoassays The estimated lower reference limit for the 30 min cortisol response to ACTH defined as the 25th percentile of log-transformed concentrations will be determined in this healthy population and used as a cut-off in the patient groups studied
To establish valid serum total cortisol and salivary cut-offs for use with the short Synacthen test in patients with normal CBG concentrations
To investigate using current assays the effect of assay differences on the serum total cortisol cut-off
To explore the performance of these cut-offs in groups of patients with suspected adrenal insufficiency and high and low serum CBG concentration
Methodology An ACTH test 250 micrograms iv ACTH1-24 will be undertaken in healthy volunteers women taking an oestrogen-containing oral contraceptive pill OCP patients with adrenal insufficiency and patients with low serum albumin Serum cortisol in the samples collected from healthy volunteers will be measured using GC-MS Advia Centaur Siemens Architect Abbott Modular Analytics E170 Roche Immulite 2000 Siemens and Access Beckman automated immunoassays The estimated lower reference limit for the 30 min cortisol response to ACTH defined as the 25th percentile of log-transformed concentrations will be determined in this healthy population and used as a cut-off in the patient groups studied
Detailed Description:
Synacthen is a synthetic analogue of ACTH which has been used since the 1960s to assess adrenal sufficiency It is now well established as a first line test to investigate diseases of the hypothalamo-pituitary-adrenal axis and to assess adrenal function in patients on long-term corticosteroid therapy Briefly cortisol is measured before and after injection of 250 micrograms of Synacthen In a normal individual serum cortisol will rise to concentrations greater than an arbitrary value typically 550 nmoll 30 minutes after administration of Synacthen
In 2004 the All Wales Clinical Biochemistry Audit group surveyed protocols for performing and interpreting short Synacthen tests This identified wide differences in practice within Wales As a result standards were drawn up for performance of the test It was noted that there was considerable variability or bias between cortisol immunoassays and that the cortisol cut-off chosen for interpretation of the short Synacthen test should be method dependent
Clark et al in 1998 reported cortisol cut-offs following Synacthen using 4 well established commercially available cortisol immunoassays This study demonstrated considerable differences between the cortisol immunoassays used in clinical laboratories at the time It was also apparent that there were differences in gender-related responses to Synacthen although there was no dependence on age In the 8 years since publication of this study there have been advances in formulation of cortisol immunoassays as well as the instrumentation used to perform analyses At the University Hospital of Wales cortisol is currently assayed using the Bayer Centaur automated immunoassay analyser This assay was not available at the time of the study by Clark et al The investigators current short Synacthen test cut-offs therefore rely on historical reference ranges which have become outdated A re-evaluation of the cortisol cut-off is required to ensure that patients are not incorrectly classified
It has been long been recognised that oestrogens including ethinyloestradiol prescribed in combined oral contraceptive pills increase total but not free serum cortisol levels The degree of increase is related to the dose used and is thought to be due to an elevation in cortisol binding globulin CBG However no comparisons of total serum cortisol in response to Synacthen have been performed between women taking oestrogens and those who are not Knowledge of the salivary cortisol response may also be useful in patients with decreased serum CBG concentrations eg severe nephrotic syndrome in whom the serum cortisol response may be misleading The investigators therefore plan to measure salivary cortisol as part of the investigators study protocol to assess the response of free cortisol
17 Hydroxyprogesterone 17OHP is an intermediate in the biosynthesis of cortisol Deficiency of 21-hydroxylase enzyme activity leads to an increased concentration of 17OHP in the peripheral circulation The short Synacthen test can be used to assist in diagnosis of mild cases of congenital adrenal hyperplasia Current reference ranges are taken from the literature
In 2004 the All Wales Clinical Biochemistry Audit group surveyed protocols for performing and interpreting short Synacthen tests This identified wide differences in practice within Wales As a result standards were drawn up for performance of the test It was noted that there was considerable variability or bias between cortisol immunoassays and that the cortisol cut-off chosen for interpretation of the short Synacthen test should be method dependent
Clark et al in 1998 reported cortisol cut-offs following Synacthen using 4 well established commercially available cortisol immunoassays This study demonstrated considerable differences between the cortisol immunoassays used in clinical laboratories at the time It was also apparent that there were differences in gender-related responses to Synacthen although there was no dependence on age In the 8 years since publication of this study there have been advances in formulation of cortisol immunoassays as well as the instrumentation used to perform analyses At the University Hospital of Wales cortisol is currently assayed using the Bayer Centaur automated immunoassay analyser This assay was not available at the time of the study by Clark et al The investigators current short Synacthen test cut-offs therefore rely on historical reference ranges which have become outdated A re-evaluation of the cortisol cut-off is required to ensure that patients are not incorrectly classified
It has been long been recognised that oestrogens including ethinyloestradiol prescribed in combined oral contraceptive pills increase total but not free serum cortisol levels The degree of increase is related to the dose used and is thought to be due to an elevation in cortisol binding globulin CBG However no comparisons of total serum cortisol in response to Synacthen have been performed between women taking oestrogens and those who are not Knowledge of the salivary cortisol response may also be useful in patients with decreased serum CBG concentrations eg severe nephrotic syndrome in whom the serum cortisol response may be misleading The investigators therefore plan to measure salivary cortisol as part of the investigators study protocol to assess the response of free cortisol
17 Hydroxyprogesterone 17OHP is an intermediate in the biosynthesis of cortisol Deficiency of 21-hydroxylase enzyme activity leads to an increased concentration of 17OHP in the peripheral circulation The short Synacthen test can be used to assist in diagnosis of mild cases of congenital adrenal hyperplasia Current reference ranges are taken from the literature
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None