Interpretation of the short Synacthen test in the presence of low cortisol-binding globulin: two case reports

Ann Clin Biochem 2006;43:416-419
© 2006 Association for Clinical Biochemistry


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Case Reports

Robert Moisey,
Dianne Wright,
Mo Aye,
Elaine Murphy and
Steven R Peacey

Department of Diabetes and Endocrinology, Bradford Teaching Hospitals NHS Trust, Duckworth Lane, Bradford BD9 6RJ, UK

Context: Ten percent of serum total cortisol (TC) is unbound;the remainder is bound to cortisol-binding globulin (CBG) and,to a lesser extent, albumin. CBG concentrations can drop significantly,particularly in critical illness, resulting in a low TC althoughthe free, active, cortisol may be normal or increased. In thecontext of a low CBG, the diagnosis of pituitary-adrenal insufficiencywith measurements of TC is difficult.

Objective: To remind clinicians of the difficulty in interpretingTC when the CBG is low, the circumstances when CBG concentrationsmay decrease and that measurement of CBG and calculation ofthe free cortisol index can help in the assessment of pituitary-adrenalreserve.

Case: We present two patients at risk of primary and secondary adrenal insufficiency with a poor response to 250 µg Synacthen.In both cases we confirmed low CBG concentrations but a normalfree cortisol index (FCI), confirming normal pituitary-adrenalreserve.

Intervention: In case one, we have been able to avoid long-termsteroid replacement therapy. We continue to reduce the steroiddose in case 2 but have been limited by the need for high-dosesteroid treatment for exacerbations of the patient’s airwaysdisease.

Conclusion: The use of TC in the assessment of the hypothalamic-pituitary-adrenal(HPA) axis may give rise to misleading results if the CBG concentrationis low. The FCI may be a better marker of pituitary-adrenalreserve in these subjects. Clinicians should be cautious wheninterpreting abnormal cortisol results and we emphasize theimportance of good clinical assessment.

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