An improved computational method to assess pituitary responsiveness to secretagogue stimuli

Objective: The quantitative assessment of gland responsiveness to exogenous stimuli is typically carried out using the peak value of the hormone concentrations in plasma, the area under its curve (AUC), or through deconvolution analysis. However, none of these methods is satisfactory, due to either sensitivity to measurement errors or various sources of bias. The objective was to introduce and validate an easy-to-compute responsiveness index, robust in the face of measurement errors and interindividual variability of kinetics parameters. Design: The new method has been tested on responsiveness tests for the six pituitary hormones (using GH-releasing hormone, thyrotrophin-releasing hormone, gonadotrophin-releasing hormone and corticotrophin-releasing hormone as secretagogues), for a total of 174 tests. Hormone concentrations were assayed in six to eight samples between -30 min and 120 min from the stimulus. Methods: An easy-to-compute direct formula has been worked out to assess the 'stimulated AUC', that is the part of the AUC of the response curve depending on the stimulus, as opposed to pre- and post-stimulus spontaneous secretion. The weights of the formula have been reported for the six pituitary hormones and some popular sampling protocols. Results and Conclusions: The new index is less sensitive to measurement error than the peak value. Moreover, it provides results that cannot be obtained from a simple scaling of either the peak value or the standard AUC. Future studies are needed to show whether the reduced sensitivity to measurement error and the proportionality to the amount of released hormone render the stimulated AUC indeed a valid alternative to the peak value for the diagnosis of the different pathophysiological states, such as, for instance, GH deficits.