ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 25 OC3.2

Determination of method-specific normal cortisol responses to the short Synacthen test

Nadia El-Farhan1,2, Alan Pickett1, David Ducroq3, Catherine Bailey4, Kelly Parham5, Nicola Morgan6, Anne Armston7, Carol Evans1 & Dafydd Aled Rees2


1University Hospital of Wales, Cardiff, UK; 2Cardiff University, Cardiff, UK; 3Welsh External Quality Assurance Scheme Laboratory, Cardiff, UK; 4Royal Gwent Hospital, Newport, UK; 5Prince Charles Hospital, Merthyr Tydfil, UK; 6Bristol Royal Infirmary, Bristol, UK; 7Southampton General Hospital, Southampton, UK.


Introduction and aims: The short Synacthen test (SST) is used to diagnose underactivity of the HPA axis, with a cortisol response <550 nmol/l at 30 min widely accepted as diagnostic of adrenal insufficiency. Earlier studies of the SST have shown variation in cortisol concentrations measured by different immunoassays, suggesting the need for method-specific cut-offs. We sought to define the cortisol response to Synacthen in healthy volunteers (HV) and establish method-specific lower reference limits (LRL) for this response.

Methods: R+D, MHRA and ethical approval were obtained. A SST was undertaken in 165 HV (age 20–66 years, 105 female, 24 taking an oral contraceptive pill (OCP)). Serum cortisol was measured using GC–MS, Siemens (Centaur and Immulite), Abbott, Roche and Beckmann automated immunoassays. The estimated LRL for the 30 min cortisol response to Synacthen was derived from the 2.5th percentile of log-transformed concentrations.

Results: The GC–MS-measured cortisol response was normally distributed in males but not females, with no significant gender difference in concentration. Immunoassay cortisol was normally distributed in all subjects, with significant gender differences in the Abbott, Roche and Beckmann assays. Immunoassays were positively biased relative to GC–MS, except in samples from women on the OCP. The estimated LRL for cortisol is method-specific, and, for the Roche assay, also gender-specific. A separate LRL is necessary for women on the OCP.

Table 1 Estimated LRL for cortisol (nmol/l).
GC–MSCentaurAbbottRocheImmuliteBeckmann
Adults420.4498.7430.4M 573.5F 524.4474.4458.6
OCP Females649.4682.3577.0791.2687.7603.8

Conclusions: This is the largest study to examine cortisol responses to Synacthen in healthy volunteers and provides clinical laboratories with method-specific estimated lower cortisol limits for the SST. We recommend the use of separate cut-offs in women on the OCP, and warn users that cortisol measurements in this subgroup are subject to assay interference.

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