Determination of Method-specific Normal Cortisol and Adrenal Hormone Responses to the Short Synacthen Test
Information source: Cardiff University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy; Adrenal Insufficiency; Hypopituitarism
Intervention: Synacthen (Tetracosactrin) (Drug)
Phase: Phase 4
Status: Active, not recruiting
Sponsored by: Cardiff University Official(s) and/or principal investigator(s): Aled Rees, MB BCh, PhD, Principal Investigator, Affiliation: Cardiff University
Summary
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 nmol/l) 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Synacthen® test cut-offs therefore rely on historical reference ranges which have become
outdated.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 e. g. 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.
Clinical Details
Official title: Determination of Method-specific Normal Cortisol and Adrenal Hormone Responses to the Short Synacthen Test
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Primary outcome: The primary end-point of the study will be to establish method dependent cortisol cut offs for the normal response to Synacthen® using the 5th percentile.
Secondary outcome: Cortisol measurements by immunoassay will be compared with the GC-MS gold standard method for normal volunteers and patients with hypopituitarism and hypoadrenalism.Synacthen® responses in women taking ethinyloestradiol-containing contraceptive pills will be compared with those who are not. We will establish cut offs for the salivary cortisol response to Synacthen® in normal volunteers using the 5th percentile. We will establish a 17OHP cut off in response to Synacthen® in normal female volunteers using the 5th percentile.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Volunteers will be in self-proclaimed good health
- Volunteers will be free of illness on the day of testing
- Volunteers will not be taking drug therapy.
- Patients will be free of intercurrent illness on the day of testing
- Patients will have a confirmed diagnosis of hypoadrenalism or hypopituitarism
Exclusion Criteria:
- Is pregnant or lactating. Females of childbearing potential must have a negative
pregnancy test before enrollment onto the study. Non-child bearing potential is
defined as post-menopausal for at least 1 year, surgical sterilisation or
hysterectomy at least three months before the start of the study,
- Is using corticosteroids,
- has any significant intercurrent disease,
- has a history of thyroid or other autoimmune disease,
- has a previous history of hypersensitivity to Synacthen®,
- has a previous history of asthma
- has a history of allergic disorder
- has any mental condition rendering the patient unable to understand the nature or
possible consequences of the study, and/or evidence of an uncooperative attitude.
Locations and Contacts
Clinical Research Facility, University Hospital of Wales, Cardiff, South Glamorgan CF14 4XW, United Kingdom
Additional Information
Starting date: September 2008
Last updated: February 24, 2010
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