Combined amplification of the pulsatile and basal modes of adrenocorticotropin and cortisol secretion in patients with Cushing's disease: Evidence for decreased responsiveness of the adrenal glands

G. Van den Berg, M. Frolich, Johannes D Veldhuis, F. Roelfsema

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Abstract

We investigated 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 23 healthy controls. Blood samples were taken at 10-min intervals, and data were analyzed with a multiparameter deconvolution technique. The patients had the same number of ACTH pulses per 24 h as the controls (34 vs. 32/24 h) and similar plasma ACTH half-lives (17.4 ± 0.7 vs. 19.3 ± 0.5 min). The mass of ACTH secreted per pulse was increased, which was caused by an increased maximal secretion rate and prolonged secretion burst duration. The number of resolved cortisol pulses was less than that for ACTH, but higher in patients than in controls (24 vs. 17/24 h), with similar half-lives in both groups (57 ± 2 vs. 59 ± 4 min). The mass of cortisol secreted per pulse was higher in patients than in controls due to an increased maximal secretion rate attained within each burst. The mean total mass of 24-h cortisol production was 12.8 mg in controls (range, 6.7-20 mg) and 46 mg (range, 13.4-154) in patients. Basal secretion rates of ACTH and cortisol were increased 19-fold (ACTH) and 7-fold (cortisol) above control values in patients with Cushing's disease (P < 0.0002). The ratio of total 24-h cortisol and ACTH production (in mass units per L distribution volume) was 23 ± 1.9 in controls and 11 ± 2.3 in patients (P < 0.001). The secretory parameters for ACTH showed strong diurnal rhythms in control subjects, but were not significant in six patients. Diurnal rhythms for cortisol could be detected in only five patients. From these observations we conclude that cortisol and ACTH release in Cushing's disease is highly pulsatile, with the preservation of diurnal properties in only some patients. Markedly amplified total daily hormone secretion was attributed to a 19-fold (ACTH) and 7-fold (cortisol) higher basal secretion rate, increased secretory burst mass (ACTH and cortisol), and frequency (cortisol) in Cushing's disease. In addition, the apparent response of the adrenal gland to increased ACTH levels is diminished, suggesting decreased responsiveness of the adrenal glands.

Original languageEnglish (US)
Pages (from-to)3750-3757
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number12
StatePublished - 1995
Externally publishedYes

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Pituitary ACTH Hypersecretion
Adrenal Glands
Adrenocorticotropic Hormone
Amplification
Hydrocortisone
Circadian Rhythm
Secretory Rate
Deconvolution

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{e44f0e9d8a5841caad4e139c683e3f28,
title = "Combined amplification of the pulsatile and basal modes of adrenocorticotropin and cortisol secretion in patients with Cushing's disease: Evidence for decreased responsiveness of the adrenal glands",
abstract = "We investigated 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 23 healthy controls. Blood samples were taken at 10-min intervals, and data were analyzed with a multiparameter deconvolution technique. The patients had the same number of ACTH pulses per 24 h as the controls (34 vs. 32/24 h) and similar plasma ACTH half-lives (17.4 ± 0.7 vs. 19.3 ± 0.5 min). The mass of ACTH secreted per pulse was increased, which was caused by an increased maximal secretion rate and prolonged secretion burst duration. The number of resolved cortisol pulses was less than that for ACTH, but higher in patients than in controls (24 vs. 17/24 h), with similar half-lives in both groups (57 ± 2 vs. 59 ± 4 min). The mass of cortisol secreted per pulse was higher in patients than in controls due to an increased maximal secretion rate attained within each burst. The mean total mass of 24-h cortisol production was 12.8 mg in controls (range, 6.7-20 mg) and 46 mg (range, 13.4-154) in patients. Basal secretion rates of ACTH and cortisol were increased 19-fold (ACTH) and 7-fold (cortisol) above control values in patients with Cushing's disease (P < 0.0002). The ratio of total 24-h cortisol and ACTH production (in mass units per L distribution volume) was 23 ± 1.9 in controls and 11 ± 2.3 in patients (P < 0.001). The secretory parameters for ACTH showed strong diurnal rhythms in control subjects, but were not significant in six patients. Diurnal rhythms for cortisol could be detected in only five patients. From these observations we conclude that cortisol and ACTH release in Cushing's disease is highly pulsatile, with the preservation of diurnal properties in only some patients. Markedly amplified total daily hormone secretion was attributed to a 19-fold (ACTH) and 7-fold (cortisol) higher basal secretion rate, increased secretory burst mass (ACTH and cortisol), and frequency (cortisol) in Cushing's disease. In addition, the apparent response of the adrenal gland to increased ACTH levels is diminished, suggesting decreased responsiveness of the adrenal glands.",
author = "{Van den Berg}, G. and M. Frolich and Veldhuis, {Johannes D} and F. Roelfsema",
year = "1995",
language = "English (US)",
volume = "80",
pages = "3750--3757",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "12",

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T1 - Combined amplification of the pulsatile and basal modes of adrenocorticotropin and cortisol secretion in patients with Cushing's disease

T2 - Evidence for decreased responsiveness of the adrenal glands

AU - Van den Berg, G.

AU - Frolich, M.

AU - Veldhuis, Johannes D

AU - Roelfsema, F.

PY - 1995

Y1 - 1995

N2 - We investigated 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 23 healthy controls. Blood samples were taken at 10-min intervals, and data were analyzed with a multiparameter deconvolution technique. The patients had the same number of ACTH pulses per 24 h as the controls (34 vs. 32/24 h) and similar plasma ACTH half-lives (17.4 ± 0.7 vs. 19.3 ± 0.5 min). The mass of ACTH secreted per pulse was increased, which was caused by an increased maximal secretion rate and prolonged secretion burst duration. The number of resolved cortisol pulses was less than that for ACTH, but higher in patients than in controls (24 vs. 17/24 h), with similar half-lives in both groups (57 ± 2 vs. 59 ± 4 min). The mass of cortisol secreted per pulse was higher in patients than in controls due to an increased maximal secretion rate attained within each burst. The mean total mass of 24-h cortisol production was 12.8 mg in controls (range, 6.7-20 mg) and 46 mg (range, 13.4-154) in patients. Basal secretion rates of ACTH and cortisol were increased 19-fold (ACTH) and 7-fold (cortisol) above control values in patients with Cushing's disease (P < 0.0002). The ratio of total 24-h cortisol and ACTH production (in mass units per L distribution volume) was 23 ± 1.9 in controls and 11 ± 2.3 in patients (P < 0.001). The secretory parameters for ACTH showed strong diurnal rhythms in control subjects, but were not significant in six patients. Diurnal rhythms for cortisol could be detected in only five patients. From these observations we conclude that cortisol and ACTH release in Cushing's disease is highly pulsatile, with the preservation of diurnal properties in only some patients. Markedly amplified total daily hormone secretion was attributed to a 19-fold (ACTH) and 7-fold (cortisol) higher basal secretion rate, increased secretory burst mass (ACTH and cortisol), and frequency (cortisol) in Cushing's disease. In addition, the apparent response of the adrenal gland to increased ACTH levels is diminished, suggesting decreased responsiveness of the adrenal glands.

AB - We investigated 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 23 healthy controls. Blood samples were taken at 10-min intervals, and data were analyzed with a multiparameter deconvolution technique. The patients had the same number of ACTH pulses per 24 h as the controls (34 vs. 32/24 h) and similar plasma ACTH half-lives (17.4 ± 0.7 vs. 19.3 ± 0.5 min). The mass of ACTH secreted per pulse was increased, which was caused by an increased maximal secretion rate and prolonged secretion burst duration. The number of resolved cortisol pulses was less than that for ACTH, but higher in patients than in controls (24 vs. 17/24 h), with similar half-lives in both groups (57 ± 2 vs. 59 ± 4 min). The mass of cortisol secreted per pulse was higher in patients than in controls due to an increased maximal secretion rate attained within each burst. The mean total mass of 24-h cortisol production was 12.8 mg in controls (range, 6.7-20 mg) and 46 mg (range, 13.4-154) in patients. Basal secretion rates of ACTH and cortisol were increased 19-fold (ACTH) and 7-fold (cortisol) above control values in patients with Cushing's disease (P < 0.0002). The ratio of total 24-h cortisol and ACTH production (in mass units per L distribution volume) was 23 ± 1.9 in controls and 11 ± 2.3 in patients (P < 0.001). The secretory parameters for ACTH showed strong diurnal rhythms in control subjects, but were not significant in six patients. Diurnal rhythms for cortisol could be detected in only five patients. From these observations we conclude that cortisol and ACTH release in Cushing's disease is highly pulsatile, with the preservation of diurnal properties in only some patients. Markedly amplified total daily hormone secretion was attributed to a 19-fold (ACTH) and 7-fold (cortisol) higher basal secretion rate, increased secretory burst mass (ACTH and cortisol), and frequency (cortisol) in Cushing's disease. In addition, the apparent response of the adrenal gland to increased ACTH levels is diminished, suggesting decreased responsiveness of the adrenal glands.

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