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.

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 intra-series 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.