Objective: Evaluate the influence of altered cortisol binding globulin (CBG) concentration on total cortisol and calculated free cortisol (CFC) during the 250 μg ACTH test.
Methods: We included 100 unmedicated healthy individuals (HI) (50M:50F), 13 women taking oral contraception (OC), and 5 men with nefrotic syndrome (NS, prior to glucocorticoid treatment; hypoalbuminaemia <9 g/l; proteinuria >1.6 g/24 h). An ACTH-test was performed between 0800 and 1000, after an overnight fast, administering 250 μg ACTH intravenously. Blood was collected at baseline and 30 min. and analysed for cortisol and CBG. CFC was calculated from Coolens formula1. Approved by local Ethical Committee.
Results: Baseline and stimulated total cortisol concentrations were 23 fold higher in OC compared to HI and NS (P<0.0001), HI and NS not differing significantly. Accordingly, OC showed 23 times elevated CBG compared to HI and NS. CBG concentrations remained unchanged in all groups during stimulation.
Baseline CFC was significantly elevated in NS compared to HI and OC (75.6 (31.599.4) (median (range)) vs. 23.3 nmol/l (12.832.2) and 24.1 nmol/l (6.760.0), respectively; P<0.005), HI and OC not differing significantly. After stimulation, CFC remained elevated in NS compared to the other groups (P<0.01)), whereas post-stimulatory CFC was lower in OC compared to HI and NS (31.6 (24.940.5) vs. 64.5 (31.8185.0) and 87.5 (66.4163.7), respectively; P<0.0001).
Conclusion: Altered CBG concentrations highly affect total cortisol. Baseline CFC has been shown to be within the normal range in patients with altered CBG concentrations and otherwise normal adrenocortical function. CFC has therefore been advocated as an alternative to total cortisol in the evaluation of the adrenocortical function in those cases. Focusing on the stimulated CFC we conclude that in OC women it is difficult to perpetuate the total as well as indices of free cortisol in the evaluation of the adrenocortical function. Elevated CFC in NS is possibly explained by active disease.
1. Coolens, JL. J Steroid Biochem 26: 197202 1987.
01 - 05 Apr 2006
European Society of Endocrinology