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Ann Clin Biochem. 2009 Nov;46(Pt 6):505-7. doi: 10.1258/acb.2009.009030. Epub 2009 Sep 2.

Serum total cortisol and free cortisol index give different information regarding the hypothalamus-pituitary-adrenal axis reserve in patients with liver impairment.

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Department of Chemical Pathology, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK.



The short synacthen test (SST) is used to investigate patients with suspected hypothalamus-pituitary-adrenal (HPA) axis pathology. A rise of serum total cortisol (total cortisol) above 550 nmol/L is accepted as sufficient adrenal reserve. In total, 80% of cortisol is bound to cortisol-binding globulin (CBG) and 10% to albumin. In the acute phase responses CBG concentrations decrease and can influence the interpretation of SST. The free cortisol index (FCI) is a surrogate marker for free cortisol and is defined as total cortisol (nmol/L)/CBG (mg/L) with an FCI > 12 representing sufficient adrenal reserve. The aim of this study was to compare total cortisol and FCI in the interpretation of SST in patients with liver impairment.


SST was done on 26 patients with liver impairment. Total cortisol was measured on Advia Centaur; serum CBG by radioimmunoassay and FCI calculated.


Eleven (42%) patients had a total cortisol >550 nmol/L (range 555-2070) and FCI > 12 (12.0-68.9) suggesting sufficient cortisol reserve. Three patients (13%) had total cortisol <550 nmol/L (268-413) and FCI < 12 (3.5-11.6) consistent with cortisol deficiency. Twelve patients (46%) had a total cortisol <550 nmol/L (144-529), but an FCI > 12 (12.0-52.9). None of the patients had a total cortisol >550 nmol/L and FCI < 12.


When total cortisol alone is used to interpret SST in patients with liver impairment, 46% may have been classified as having adrenal insufficiency because of low CBG. FCI may be better for the evaluation of HPA axis insufficiency in patients with liver impairment.

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