Intensive Venous Sampling Paradigms Disclose High Frequency Adrenocorticotropin Release Episodes in Normal Men*

Abstract

Recent studies in the rat and rhesus monkey have disclosed apparently high frequency in vivo ACTH release episodes. While the circadian pattern of plasma ACTH concentrations has been known for many years, the exact frequency of ultradian pulsatile ACTH release in man is not clear, due in part to variable intensities of blood-sampling schedules and the limited availability of sensitive ACTH assays. In this study we used a new sensitive and specific immunoradiometric assay to measure plasma ACTH concentrations in blood sampled at 1) 2-min intervals for 3 h, followed by 4-min intervals for 4 more h in six men; and 2) 10-min intervals for 24 h in eight other men. An objective peak detection algorithm (Cluster) and cosinor analyses were used to assess the episodic pulsatility and circadian rhythmicity of ACTH. Comparisons were made among the 2 min (3 h), 4, 8, and 12 min (7 h), and 10 min (24 h) time series. Mean ACTH interpulse intervals were significantly different among the five sampling groups (P less than 0.00001). Sampling every 2 min yielded a mean ACTH interpulse interval of 18 min, which was significantly shorter than the mean interpulse intervals of 35, 53, 52, and 73 min resulting, respectively, from sampling every 4, 8, 10, and 12 min (P less than 0.05). In contrast, maximal peak ACTH amplitudes (picomoles per L or percent increase) did not vary as a function of sampling frequency. The 24-h plasma ACTH concentration time series showed significant diurnal variation, with a mean circadian amplitude of 0.95 +/- 0.15 pmol/L occurring at 1008 h (+/- 25 min). Cosinor analysis of various ACTH pulse parameters deduced from the 24-h time series revealed significant circadian rhythmicity in the ACTH peak maxima (P less than 0.05), peak increments (P less than 0.05), and prepeak nadir (P less than 0.05) concentrations, but not in ACTH interpulse intervals. We conclude that in men, 1) intensive sampling at 2-min intervals unmasks high frequency ACTH release episodes that cannot be detected at conventional sampling rates; and 2) ACTH peak amplitude, but not frequency, varies significantly during the course of circadian changes in the plasma ACTH concentrations.

Twenty-Four-Hour ACTH and Cortisol Pulsatility in Depressed Women

“…The older algorithms such as Cluster or Pulsar detect few pulses (10 or 6.4 pulses/24 hr) than newer pulse detection algorithms such as deconvolution, which found 40 pulses in 24 hr. Our estimate of 23 and 26 secretory episodes per 24 hr is intermediate between the number of pulses observed by Iranmanesh et al (1990) with deconvolution and that detected by Cluster or Pulsar. Our data do not show any difference in patients and controls in pulse number.…”

“…The report of Mortola et al (1987) examined six patients and reported an increase in ACTH pulse frequency. However, the number of pulses of ACTH found by Mortola et al (1987), 9.9 pulses in 24 hr in controls, using Cluster to detect ACTH pulses is significantly less than the number found by Veldhuis and colleagues (40 pulses) in normal men using the newer deconvolution analysis Johnson 1992, 1986;Iranmanesh et al 1990). Finally, while HPA axis overactivity in depression is the usual type of HPA axis dysregulation that is observed, Gold and colleagues have proposed, based upon data from patients with chronic fatigue syndrome and fibromyalgia, that patients with atypical depression manifest a hypoactive HPA axis and an underactive CRH neuron in the paraventricular nucleus (Crofford et al 1994;Demitrack et al 1991;Tsigos and Chrosous 1994).…”

Cortisol feedback state governs adrenocorticotropin secretory-burst shape, frequency, and mass in a dual-waveform construct: time of day-dependent regulation

“…ACTH was quantitated in duplicate by high-sensitivity robotics-automated immunoradiometric assay with median within-and between-assay coefficients of variation (CV) of 5.2 and 6.1%, respectively (13,38). Cortisol was assayed by solid-phase RIA (37).…”

Effects of Low- and High-Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men

“…Moreover, samples for ACTH and/or cortisol analysis usually were collected at relatively infrequent intervals, or as single daily samples (Seyler et al, 1984(Seyler et al, , 1986Baron et al, 1995;Pickworth and Fant, 1998;del Arbol et al, 2000), and plasma nicotine levels were seldom measured. Because ACTH is released from corticotropes in the anterior pituitary in rapid bursts of short duration (3-10 min) (Iranmanesh et al, 1990), frequent blood sample collection is important to measure accurately drug effects on hormone release patterns (Teoh et al, 1994;Sarnyai et al, 1995). Moreover, rapid sample collection is essential to assess the temporal relationship between anterior pituitary and adrenal hormones, cardiovascular measures, and the subjective reports during cigarette smoking.…”