How does one get at glandular secretion, when only hormone concentrations are measured?

The paper by Sartorioet al. (1997) in this issue illustrates the merit of collaboration among statisticians, engineers, mathematicians and clinical scientists. Sartorio et al. have made a valuable investigative contribution to clinical endocrinology by introducing a non-parametric approach to calculating underlying hormone secretion from serum hormone concentration measures, given information about the hormone half-life. The class of methods by which such calculations are accomplished is known as ‘deconvolution analysis’. This term originates from the etymological sense of ‘to unravel, disentwine, or untangle’. Thus, assuming knowledge of a hormone’s half-life, and given serial serum hormone concentrations measured in blood samples obtained repetitively, one can estimate (unravel) the underlyingsecretoryactivity that created the observed plasma hormone pulse(s) profile, via one or more of an array of specific computer-assisted deconvolution techniques (reviewed Veldhuis & Johnson, 1991). Several exciting deconvolution tools for neuroendocrinological studies have evolved over the last few decades. Such methods have almost invariably shown that hormone secretion is not instantaneous (McIntosh et al., 1988; Veldhuiset al., 1994). Moreover, direct sampling of pituitary blood in the horse, rat and sheep indicates that hormone secretory bursts are indeed of significant (several minutes) duration. Other studies suggest that pathophysiological conditions can influence the duration of underlying hormone secretory pulses; e.g. GH bursts in Turner’s syndrome (Veldhuis et al., 1991), basal and exogenous GnRH-stimulated LH secretion throughout the menstrual cycle (Sollenberger et al., 1990a,b), in postmenopausal women treated with oestrogen (Quyyumi et al., 1993), and ACTH release as stimulated by electroconvulsive shock therapy versus insulin injection (Iranmanesh et al., 1993). Importantly, deconvolution analysis allows one to examine the underlying secretory behaviour of an endocrine organ by adjusting for hormone-specific half-life. This is not a trivial matter, since hormone half-lives can be as short as 2–3 minutes in the case of insulin or PTH, or as long as 1 hour for LH and 8–13 hours for FSH. The remarkably different half-lives of various hormones that are secreted in a pulsatile manner greatly alter their concentration values in blood, and the resultant pulse profiles (Veldhuiset al., 1990). However, after disentangling the effects of hormone half-life from the observed hormone concentration profile, the underlying secretory activity seems to be substantially conserved among different endocrine organs, revealing in most cases a dominantly pulsatile mode with some variable (or in other cases negligible) basal hormone release. The work by Sartorioet al. is of interest as a further tool for clinical investigators appraising underlying secretory signals. The non-parametric aspect is an important contribution, since this method, like several others introduced within the last 5 years, is waveform-independent, that is, no a priori assumed hormone secretory pulse shape is required for the analysis (Veldhuis & Johnson, 1991; Munson & Rodbard, 1989; Hindmarsh et al., 1990; Albertsson-Wiklandet al., 1989; McIntosh et al., 1988; Veldhuiset al., 1994; Johnson & Veldhuis, 1995). In addition, the authors quite appropriately remind one to optimize the blood sampling schedule to the problem at hand, and to obtain relevant hormone half-life information, including estimates of its anticipated variability in a relevant population. Implied plans in the report of Sartorio et al. are, first, to extend the non-parametric method to pulse detection per se, which was here applied to a single GHRH-stimulated GH release episode. Secondly, the methodology should be implemented for longer (e.g. 24-hour) time series. And, thirdly, it should be applied to appraise secretion of other hormones. Indeed, several available deconvolution techniques can evaluate entire 24-hour hormone profiles so as to estimate the number, amplitude, duration, and mass of underlying secretory events, in some cases with concurrent estimates of hormone half-life and/or basal hormone release (Veldhuis et al., 1994). A significant advantage of evaluating underlying secretory activity from serum hormone concentration data (deconvolution) is the ability to dissect overlapping secretory peaks, the individual contributions of which are otherwise difficult to assess, e.g. quantitative in vivo dose–response experiments (Quyyumiet al., 1993; Veldhuiset al., 1989) and in evaluating desensitization of stimulated secretion (Urban et al., 1991; Mauraset al., 1991). Notably, given overlapping concentration pulses, the amount of hormone actually secreted in response to each injected dose can be estimated correctly if one ‘subtracts’ the amount of hormone still present in the blood due to peaks produced earlier in the same experiment. Deconvolution provides a way to accomplish this. Unresolved queries and caveats in this field include a number Commentary