Reliability of hormonal levels for assessing the hypothalamic‐pituitary‐ adrenocortical system in clinical pharmacology.

Abstract

Few data are available on the reliability of measurements of adrenocortical and corticotroph hormones for use in clinical pharmacology. Two placebo controlled crossover trials in 20 normal healthy male subjects offered the opportunity to perform three repeat samplings of adrenocortical and corticotroph hormones at 1 to 5 week intervals during the placebo periods. Measurements of baseline levels of plasma, salivary and urinary cortisol, plasma adrenocorticotroph hormone (ACTH), lipotrophic hormone (LPH), ,-endorphin, post tetracosactrin levels of plasma and salivary cortisol, post corticotrophin releasing hormone (CRH)-lysine vasopressine (LVP) levels of plasma cortisol, ACTH and LPH; and post metyrapone levels of plasma cortisol and 11-deoxycortisol (compound S), ACTH, LPH, ,B-endorphin were performed in the same laboratory. The reliability of the measurements was estimated by computing the intraclass correlation coefficient (R) and by using Altman-Bland graphical method. The Rs of baseline parameters varied from 0.18 (for 08.00 h salivary cortisol) to 0.55 (for 08.00 h plasma cortisol and nocturnal urinary cortisol). In contrast, parameters obtained after direct stimulation or inhibition of the producing targets were much more reliable: Rs were above 0.80 for post tetracosactrin levels of plasma and salivary cortisol, post CRH-LVP levels of plasma ACTH and LPH. The Rs were below 0.50 for post metyrapone levels of plasma 11-deoxycortisol, ACTH, LPH and ,B-endorphin. The interval between sampling did not affect R estimates. These data show that peak levels of plasma cortisol and ACTH after direct stimulation are highly reliable whereas baseline and main post-metyrapone levels are not. A single post stimulation level of these hormones may suffice to characterize normal subjects in trials while three or more baseline or post-metyrapone level measurements may be needed to obtain a satisfactory reliability of the mean.

Breeding for robustness: the role of cortisol

“…Indeed, as mentioned in the previous paragraph, Brown and Nestor (1973) could select divergent lines of turkey based on their response to ACTH injection, with a realized heritability of 0.28. The same kind of variability in adrenal response to ACTH has been shown in humans Coste et al, 1994).…”

The Diurnal Cortisol Cycle in Delinquent Male Adolescents and Normal Controls

“…The influence of awakening time is still debated, with some studies reporting no influence (Wust et al, 2000), and others finding an association (Edwards et al, 2001). The CAR has a high intraindividual stability compared with single basal morning cortisol values (Coste et al, 1994). As such, the CAR could be an interesting parameter of additional value for studying HPA axis functioning.…”

Stability of the diurnal cortisol profile in children and adolescents

“…Thus, several studies have examined the stability of the diurnal cortisol profile in adults to guide sampling protocol decisions. A single day of sampling yields morning cortisol and awakening response values that have low stability (Coste et al, 1994;Hellhammer et al, 2007). Among the awakening response measures, AUC AG is more stable and evidences moderate stability over 2 days of sampling (ICC = 0.69), while AUC I necessitates 5 days of sampling to reach comparable reliability (ICC = 0.65; Hellhammer et al, 2007).…”