Basal, Pulsatile, Entropic (Patterned), and Spiky (Staccato-like) Properties of ACTH Secretion: Impact of Age, Gender, and Body Mass Index

Abstract

Background: Age, gender, and BMI determine ultradian modes of LH and GH secretion, viz., pulsatile, basal, pattern-defined regularity [approximate entropy (ApEn)] and spikiness (sharp, brief excursions). Whether the same determinants apply to ACTH secretion is not known. Setting: The study was conducted at a tertiary medical center. Subjects: We studied normal women (n = 22) and men (n = 26) [ages, 23–77 yr; body mass index (BMI), 21–32 kg/m²]. Methods: Volunteers underwent 10-min blood sampling to create 24-h ACTH concentration profiles. Outcomes: Dynamic measures of ACTH secretion were studied. Results: Mean ACTH concentrations (R² = 0.15; P = 0.006) and both pulsatile (R² = 0.12; P = 0.018) and basal (nonpulsatile) (R² = 0.16; P = 0.005) ACTH secretion correlated directly with BMI (n = 48). Men had greater basal (P = 0.047), pulsatile (P = 0.031), and total (P = 0.010) 24-h ACTH secretion than women, including when total secretion was normalized for BMI (P = 0.019). In men, both ACTH-cortisol feedforward and cortisol-ACTH feedback asynchrony (cross-ApEn) increased with age (R² = 0.20 and 0.22; P = 0.021 and 0.018). ACTH spikiness rose with age (P = 0.046), principally in women. Irregularity of cortisol secretion (ApEn) increased with age (n = 48; P = 0.010), especially in men. In both sexes, percentage pulsatile ACTH secretion predicted 24-h mean cortisol concentrations (R² = 0.14; P = 0.009). Conclusion: Valid comparisons of ultradian ACTH dynamics will require cohorts matched for age, gender, and BMI, conditions hitherto not satisfied in most physiological studies of this axis. ACTH secretion dynamics are jointly determined by age, gender, and body mass index. Future studies must match control and interventional groups for these primary covariates.