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Sensitivity and specificity of pulse detection using a new deconvolution method

¹Endocrine Research Unit, Department of Internal Medicine, Mayo Medical School, Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota; ²Endocrine and Metabolic Group, Woolcock Institute of Medical Research, University of Sydney and Concord Hospital, Sydney, New South Wales, Australia; ³Department of Statistics, University of Virginia, Charlottesville, Virginia; ⁴Department of Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands; ⁵Department of Pediatrics and Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan; and ⁶Division of Reproduction and Endocrinology, King's College London, London, United Kingdom

Submitted 5 February 2009 ; accepted in final form 10 June 2009

Quantifying pulsatile secretion from serial hormone concentration measurements (deconvolution analysis) requires automated, objective, and accurate detection of pulse times to ensure valid estimation of secretion and elimination parameters. Lack of validated pulse identification constitutes a major deficiency in the deconvolution field, because individual pulse size and number reflect regulated processes that are critical for the function and response of secretory glands. To evaluate deconvolution pulse detection accuracy, four empirical models of true-positive markers of pituitary (LH) pulses were used. 1) Sprague-Dawley rats had recordings of hypothalamic arcuate nucleus multiunit electrical activity, 2) ovariectomized ewes underwent sampling of hypothalamo-pituitary gonadotropin-releasing hormone (GnRH pulses), 3) healthy young men were infused with trains of biosynthetic LH pulses after GnRH receptor blockade, and 4) computer simulations of pulsatile LH profiles were constructed. Outcomes comprised sensitivity, specificity, and receiver-operating characteristic curves. Sensitivity and specificity were 0.93 and 0.97, respectively, for combined empirical data in the rat, sheep, and human (n = 156 pulses) and 0.94 and 0.92, respectively, for computer simulations (n = 1,632 pulses). For simulated data, pulse-set selection by the Akaike information criterion yielded slightly higher sensitivity than by the Bayesian information criterion, and the reverse was true for specificity. False-positive errors occurred primarily at low-pulse amplitude, and false-negative errors occurred principally with close pulse proximity. Random variability (noise), sparse sampling, and rapid pulse frequency reduced pulse detection sensitivity more than specificity. We conclude that an objective automated pulse detection deconvolution procedure has high sensitivity and specificity, thus offering a platform for quantitative neuroendocrine analyses.

luteinizing hormone; male; analytical model; biostatistics; secretion; elimination; human; rat; sheep

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