Appraising Endocrine Pulse Signals at Low Circulating Hormone Concentrations: Use of Regional Coefficients of Variation in the Experimental Series To Analyze Pulsatile Luteinizing Hormone Release

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Abstract
We have developed a regional dual-threshold method for detecting endocrine pulses at variably low hormone concentrations such as those that occur in the pediatric age group. This algorithm uses the local intraseries coefficient of variation to test for a significant increase and decrease (peak or pulse) in the experimental series. The method is unique in combining the following considerations: 1) use of internal measurement error present in the actual sample replicates (rather than that estimated from external standards); 2) an ability to accommodate a wide range of nonuniformity in intraassay coefficients of variation; 3) utilization of both upstroke and downstroke threshold criteria; and 4) adaptability to specify a physiologically relevant proximity of the postpeak nadir to the center of the peak. We have validated the behavior of this method in relation to false-positive rates for various program parameters and have illustrated the application of this new regional dual-threshold method to luteinizing hormone pulse detection in pubertal boys who have relative hypogonadotropism, which renders reliable luteinizing hormone pulse detection particularly difficult.