CORTICOSTEROID-BINDING GLOBULIN MODULATES CORTISOL CONCENTRATION RESPONSES TO A GIVEN PRODUCTION-RATE

In most clinical situations, the ability of the adrenal to produce cor tisol is studied with measurements of cortisol concentration. The vali dity of this assumes the existence of a predictable relationship betwe en cortisol production and plasma cortisol concentration. This assumpt ion was tested by determining if production rates, as simulated by con stant cortisol infusions, were predictive of the resultant plasma and urine cortisol concentrations in dexamethasone-suppressed subjects. Ad ditional attempts to predict simulated cortisol production rates were made with infusions of [9,12, 12-H-2(3)]cortisol. Thirty-six 8-h corti sol infusions were performed in 24 subjects. Although there was a tend ency to achieve a higher plasma cortisol concentration response at a h igher cortisol infusion rate (P < 0.04), the known cortisol infusion r ate was a poor predictor of plasma cortisol responses (r(2) = 0.12). A ddition of corticosteroid-binding globulin concentration (CBG) as a co variate greatly improved the predictability of plasma cortisol respons es (r(2) = 0.52). Urine free cortisol, normalized to inulin excretion, had a predictable relationship to cortisol infusion rate (r(2) = 0.82 ). Isotope-enrichment data from a group of 6 subjects receiving multip le cortisol infusions during administration of [9,12,12-H-2(3)]cortiso 1 gave the most accurate predictions of the known cortisol infusion ra tes (r(2) = 0.93). It is concluded that: 1) cortisol infusion (product ion) rate and plasma cortisol concentration are poorly correlated; 2) CBG is an important modulator of concentration responses to a given pr oduction rate; and 3) short (8-h) infusions of[9,12, 12-H-2(3)]cortiso l may be used to determine cortisol production rates in humans. The me chanisms by which CBG modulates cortisol concentration responses are e laborated in a companion report.