Corticosteroid-binding globulin modulates cortisol concentration responses to a given production rate

Area of Science:

• Endocrinology
• Metabolic Research

Background:

• Clinical assessment of adrenal function relies on measuring cortisol concentration.
• This method assumes a direct correlation between cortisol production and plasma cortisol levels.

Purpose of the Study:

• To evaluate the predictive accuracy of simulated cortisol production rates on plasma and urine cortisol concentrations.
• To assess the influence of corticosteroid-binding globulin (CBG) on cortisol levels.
• To validate the use of isotope-labeled cortisol infusions for determining cortisol production rates.

Main Methods:

• Performed 36 eight-hour cortisol infusions in 24 subjects.
• Utilized [9,12,12-2H3]cortisol infusions to predict simulated cortisol production rates.
• Measured plasma and urine cortisol concentrations, and corticosteroid-binding globulin (CBG).

Main Results:

• Cortisol infusion rate was a weak predictor of plasma cortisol concentration (r2 = 0.12).
• Including CBG concentration significantly improved prediction of plasma cortisol (r2 = 0.52).
• Urine free cortisol, normalized to inulin excretion, showed a strong correlation with cortisol infusion rate (r2 = 0.82).
• Isotope-enrichment data provided the most accurate prediction of cortisol infusion rates (r2 = 0.93).

Conclusions:

• Cortisol production rate and plasma cortisol concentration are poorly correlated.
• CBG significantly modulates plasma cortisol concentration in response to production rates.
• Short infusions of isotope-labeled cortisol are reliable for determining human cortisol production rates.