Serum total cortisol and free cortisol index give different information regarding the hypothalamus–pituitary–adrenal axis reserve in patients with liver impairment
Abstract
Background 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. Method SST was done on 26 patients with liver impairment. Total cortisol was measured on Advia Centaur; serum CBG by radioimmunoassay and FCI calculated. Results 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 12 (12.0-52.9). None of the patients had a total cortisol >550 nmol/L and FCI Conclusion 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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Patients with nephrotic syndrome, liver disease, immediate postoperative period, or requiring intensive care may have lower CBG and albumin and hence lower cortisol measurements.
“Patients with diseases such as nephrotic syndrome (43) and liver disease (50) as well as those who are in the immediate postoperative period (51) or who require intensive care (52) may have lower CBG and albumin and hence, lower cortisol measurements.”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [50]
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Coolens, J.-L., Van Baelen, H., & Heyns, W. (1987) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(87)90071-9 · Cited by 290 · see citing works
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Bornstein, S. R., Allolio, B., Arlt, W., Barthel, A., Don-Wauchope, A., Hammer, G. D., Husebye, E. S., Merke, D. P., Murad, M. H., Stratakis, C. A., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1710 · Cited by 1,769 · see citing works
“Patients with diseases such as nephrotic syndrome (43) and liver disease (50) as well as those who are in the immediate postoperative period (51) or who require intensive care (52) may have lower CBG and albumin and hence, lower cortisol measurements.”
BackgroundMeasuring cortisol in serum, urine and saliva—Are our assays good enough?
El-Farhan, N., Rees, D. A., & Evans, C. (2017) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1177/0004563216687335 · Cited by 395 · see citing works
The role of corticosteroid-binding globulin in the evaluation of adrenal insufficiency
Verbeeten, K. C., & Ahmet, A. H. (2018) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2017-0270 · Cited by 51 · see citing works
Bile acids and glucocorticoid metabolism in health and disease
Theiler-Schwetz, V., Zaufel, A., Schlager, H., Obermayer-Pietsch, B., Fickert, P., & Zollner, G. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.08.001 · Cited by 31 · see citing works
- Authors
- Vincent, R. P., Etogo-Asse, F. E., Dew, T., Bernal, W., Alaghband-Zadeh, J., & le Roux, C. W.
- Affiliations
- King's College Hospital NHS Foundation Trust (GB)
- Department of Chemical Pathology
- Venue
- Annals of Clinical Biochemistry: International Journal of Laboratory Medicine
- Publisher
- SAGE Publications
- Published
- 2009-09-02
- Volume
- 46
- Issue
- 6
- Pages
- 505-507
- ISSN
- 0004-5632 (ISSN-L)
- 1758-1001
- OpenAlex
- W2018999941
- Cited by
- 37
- References
- 2
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 1 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 5 · 2012: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Clinical Biochemistry International Journal of Laboratory Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (DHCS/05/05)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- total cortisol, corticosteroid-binding globulin, ACTH stimulation test, hypothalamic-pituitary-adrenal axis, adrenal insufficiency, liver dysfunction, acute phase response, adrenal reserve
- MeSH terms
- Adrenal Glands, Adult, Albumins, Carrier Proteins, Female, Humans, Hydrocortisone, Hypothalamus, Liver Diseases, Male, Middle Aged, Pituitary Gland, Radioimmunoassay, Retrospective Studies, Saliva
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