Intercomparison of Four Methods for Measuring Cortisol Production

Four methods of measuring the daily cortisol production rate were intercompared in 49 patients with production rates varying between 2 and 60 mg per day: a. “Urinary” production rate by isotope dilution; b. “Urinary” production rate by quantitating the excretion of endogenous THF + ATHF + THE and multiplying their sum by an empirically derived constant; c. Plasma production rate by multiplying the MCR by the 24-hr mean plasma cortisol concentration; d. Plasma production rate by summation of incremental secretion, calculated from the episodic secretory peaks defined by the 72 sample 24-hr study technique previously reportd from this laboratory. It was found that these four methods yield values whose relationships, on the average, are completely predictable: a. The two “urinary” production rates yield identical values; b. Plasma production rate by summation of incremental secretion very slightly underestimates plasma production rate by MCR, because of the small proportion (less than 19%) of the daily cortisol secretion that occurs between obvious secretory episodes; c. Plasma production rate by MCR is a constant fraction (75%) of the “urinary” production rate. The following conclusions were drawn: a. The predictable relationships observed make it possible to directly intercompare cortisol production rate data derived by any of the four methods, thereby greatly extending the amount of already published data that can be interpreted; b. The fact that the plasma production rate is a constant fraction of the “urinary” production rate appears to mean that some compound contributes to the formation or urinary cortisol metabolites without mixing with the plasma cortisol pool. Reasons are adduced for postulating that this compound is probably cortisone; c. The true adrenal secretion rate probably lies between a lower limit represented by the plasma production rate and an upper limit represented by the “urinary” production rate. The true secretion rate can therefore be measured with an error of less than 25%.