Patients with Cushing's disease secrete adrenocorticotropin and cortisol jointly more asynchronously than healthy subjects

Ferdinand Roelfsema, Steven M. Pincus, Johannes D Veldhuis

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

We examined serum concentration time-series for ACTH and cortisol in 20 patients with pituitary-dependent ACTH excess (Cushing's disease) and in 29 age- and gender-matched controls. For each subject, blood samples were obtained at 10-min intervals for 24 h. Joint ACTH-cortisol synchrony was quantified using the recently introduced cross-approximate entropy (cross- ApEn) statistic. In patients, cross-ApEn was greater than in controls (1.686 ± 0.051 vs. 1.077 ± 0.039, P = 3.45 x 10-16), giving a sensitivity of 85%. In control subjects, but not in patients, cross-ApEn was correlated positively with age (r = 0.465, P = 0.011). There was no gender difference in cross-ApEn, nor a relationship between cross-ApEn and the 24-h ACTH and cortisol secretion, in patients or controls. In contrast, the maximal cross- correlation coefficient for the ACTH and cortisol series after detrending the series was 0.394 ± 0.033 in controls and 0.297 ± 0.034 in patients with considerable overlap of the subgroups, giving a sensitivity for this index of only 5%. In addition to previous findings of increased individual irregularity of ACTH and cortisol release in Cushing's disease, we can now also demonstrate greater joint asynchrony of the circulating concentrations of these hormones. Thus, Cushing's disease disrupts ensemble network secretory dynamics over individual hormone output. We conclude that, like GH- secreting pituitary and aldosterone-secreting adrenal tumors, ACTH-secreting pituitary tumors exhibit significant loss of orderly hormone release patterns. Moreover, Cushing's disease is marked further by deterioriation of bihormonal synchrony between ACTH and cortisol release, thus suggesting further erosion of within-axis feedback control.

Original languageEnglish (US)
Pages (from-to)688-692
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number2
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Pituitary ACTH Hypersecretion
Adrenocorticotropic Hormone
Hydrocortisone
Healthy Volunteers
Hormones
Tumors
Joints
Glandular and Epithelial Neoplasms
Pituitary Neoplasms
Entropy
Aldosterone
Feedback control
Time series
Erosion
Blood
Statistics

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Patients with Cushing's disease secrete adrenocorticotropin and cortisol jointly more asynchronously than healthy subjects. / Roelfsema, Ferdinand; Pincus, Steven M.; Veldhuis, Johannes D.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 2, 1998, p. 688-692.

Research output: Contribution to journalArticle

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abstract = "We examined serum concentration time-series for ACTH and cortisol in 20 patients with pituitary-dependent ACTH excess (Cushing's disease) and in 29 age- and gender-matched controls. For each subject, blood samples were obtained at 10-min intervals for 24 h. Joint ACTH-cortisol synchrony was quantified using the recently introduced cross-approximate entropy (cross- ApEn) statistic. In patients, cross-ApEn was greater than in controls (1.686 ± 0.051 vs. 1.077 ± 0.039, P = 3.45 x 10-16), giving a sensitivity of 85{\%}. In control subjects, but not in patients, cross-ApEn was correlated positively with age (r = 0.465, P = 0.011). There was no gender difference in cross-ApEn, nor a relationship between cross-ApEn and the 24-h ACTH and cortisol secretion, in patients or controls. In contrast, the maximal cross- correlation coefficient for the ACTH and cortisol series after detrending the series was 0.394 ± 0.033 in controls and 0.297 ± 0.034 in patients with considerable overlap of the subgroups, giving a sensitivity for this index of only 5{\%}. In addition to previous findings of increased individual irregularity of ACTH and cortisol release in Cushing's disease, we can now also demonstrate greater joint asynchrony of the circulating concentrations of these hormones. Thus, Cushing's disease disrupts ensemble network secretory dynamics over individual hormone output. We conclude that, like GH- secreting pituitary and aldosterone-secreting adrenal tumors, ACTH-secreting pituitary tumors exhibit significant loss of orderly hormone release patterns. Moreover, Cushing's disease is marked further by deterioriation of bihormonal synchrony between ACTH and cortisol release, thus suggesting further erosion of within-axis feedback control.",
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