Endocrine Abstracts

Cortisol ([C]) biological activity depends on its free fraction diffusion into the intracellular compartment. The diagnosis of adrenal insufficiency requires investigations such as the synacthen test and studies in intensive care units suggest that free plasma [C] could provide a better indicator of efficient [C] than total plasma [C]. We undertook this study to compare various determinations of free [C] levels with regard to adrenal status evaluated on total plasma [C] after a 1 μg synacthen test.

Tests were performed in 130 patients from an endocrinology department (81 F) to investigate adrenal insufficiency (saliva and serum samples). We assayed saliva [C] and plasma CBG, albumin, total and free [C] (after ultrafiltration). Free cortisol (F) also estimated with quadratic equations (either with concentrations of CBG alone or CBG and albumin) or with the [C]/CBG index.

Statistically significant correlations were seen between all free [C] assays or calculations; Spearman’s ρ coefficient were: 0.85, 0.63, 0.57, 0.51 between [C] saliva and i) [C] levels in ultrafiltrated serum, ii) after quadratic calculation (CBG&Albumin), iii) after quadratic calculation (CBG) and iv) for [C]/CBG index, respectively.

When a post synacthen serum total [C] level of 550 nmol/l was used as threshold to diagnose adrenal insufficiency (36/130 patients) the ROC AUCs were: 0.97, 0.92, 0.90, 0.89, 0.83 for [C] levels in ultrafiltrated serum, after quadratic calculation (CBG&Albumin), in saliva, after quadratic calculation (CBG) and for [C]/CBG index, respectively. For a sensitivity set at 100% specificities were: 46, 40, 27, 8 and 1% for [C] levels after quadratic calculation (CBG&Albumin), in ultrafiltrated serum, in saliva, after quadratic calculation (CBG) and for [C]/CBG index, respectively.

Thus, despite good general agreement between the synacthen test and the various methods to evaluate free cortisol (except [C]/CBG index) individual discrepancies mar their use without addressing their clinical relevance in endocrinology.