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

Endocrine Research Unit (J.D.V.), Mayo Medical School, Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; Department of Endocrinology and Metabolic Diseases (F.R.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Endocrine Section (A.I.), Medical Service, Salem Veterans Affairs Medical Center, Salem, Virginia 24153; Pacific Behavioral Research Foundation (B.J.C.), Carmel, California 93922; Department of Statistics (D.M.K.), University of Virginia, Charlottesville, Virginia 22904; and Independent Mathematician (S.M.P.), Guilford, Connecticut 06437

Address all correspondence and requests for reprints to: Johannes D. Veldhuis, Endocrine Research Unit, Mayo Medical School, Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905. E-mail: veldhuis.johannes{at}mayo.edu.

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.