Characterization of the Normal Temporal Pattern of Plasma Corticosteroid Levels

Abstract

The present studies had 2 objectives: I. To delineate more precisely the time course of adrenal secretory activity in the normal human and patients with Cushing's syndrome, by measurement of plasma corticosteroid and ACTH levels half-hourly throughout the 24 hr cycle. II. To describe hitherto lacking clinically optimal and suitable conditions for determination and definition of the normal circadian pattern of plasma corticosteroid levels (CPOHCS). 1. I. Four control subjects with normal activity sleep and meal time patterns were studied: 3 were restudied during “constant feeding,” 1 was restudied during constant glucose administration and again under different dexamethasone regimens. CPOHCS consisted of 5–10 peaks in a given subject. Fifty to 75% of peaks occurred in a 9 hr period (midnight to 9:00 am) describing a gradual upward course with maximum plasma corticosteroid levels occurring 1/2–2 hr following awakening. A downward trend followed with other peaking activity occurring between 11:30 am–2:00 pm and 4:30–6:00 pm. Quiescent periods usually occurred between these intervals. There was close temporal correlation between plasma ACTH and corticosteroid peaks, but no apparent proportionality between plasma ACTH and corticosteroid levels. Dose and time of dexamethasone administration determined the duration of its effect in abolishing subsequent maximal am and other peaks: 0.5 mg at midnight (but not at 8:00 am) and 1.0 mg at 8:00 am blocked such maximal peaks. Three patients with active Cushing's syndrome (adrenal hyperplasia) showed an irregular oscillatory CPOHCS. 2. II. For clinical definition of CPOHCS, 92 nonhospitalized control subjects and 14 hospitalized normal volunteers were studied by sampling q. 4–6 hr beginning at 8:00 am. Noontime levels were not considered since half-hourly data indicated variability in the height of peaking at this time. Other sampling times (save 8:00 am) occurred within quiescent periods. Normal CPOHCS is defined as one in which all corticosteroid values after 8:00 am are less than 75% of the 8:00 am level. Age, sex and hospitalization had no effect on CPOHCS. In a given subject, corticosteroid levels and pattern were reproducible over 1- to 120-day intervals.