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.


METHODS
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.


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.
Sartorio
Alessandro
A
Laboratorio Sperimentale di Ricerche Endocrinologiche, Istituto Auxologico Italiano, IRCCS, Milan, Italy. sartorio@auxologico.it
De Nicolao
Giuseppe
G
Liberati
Diego
D
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism*; D010906:Pituitary Hormone-Releasing Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D010906:Pituitary Hormone-Releasing Hormones; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone