Circadian variation in Cushing's disease and pseudo-Cushing states by analysis of F and ACTH pulsatility

J. M. Cunningham, O. M. Buxton, Roy E. Weiss

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Distinguishing pituitary-dependent Cushing's disease from pseudo-Cushing's states can present a diagnostic challenge. Although many studies potentially discriminate between the 2, only the dexamethasone-suppressed corticotropin-releasing hormone (CRF) stimulation test at 15 minutes is 100% sensitive or specific. We measured baseline profiles of F and ACTH in 31 Cushing's disease patients, 11 with pseudo-Cushing's and 17 controls. Venous blood was collected at 30 minute intervals for 24-h. Subjects also had CRF stimulation tests and 2.0 mg/day dexamethasone suppression tests. F and ACTH profiles were analyzed for circadian rhythmicity, variability, and pulsatility. Relative circadian amplitude was decreased in Cushing's disease compared to both pseudo-Cushing's and normal states. Relative pulse amplitude was reduced in Cushing's disease. Because of this dampening of circadian and pulsatile variations, the overall variability of F and ACTH levels around their mean levels as quantified by the intra-series coefficient of variation (CV), was also decreased in Cushing's disease compared to pseudo-Cushing's and normal states. A F 24-h CV<40% was able to distinguish Cushing's disease from pseudo-Cushing's with 100% sensitivity (95% confidence interval (CI), 88-100%) and specificity (CI, 71-100%). An ACTH CV<40% had 97% sensitivity (CI, 83-100%) and 100% specificity (CI, 71-100%). An overnight 8-h F CV <40% also distinguished Cushing's disease from pseudo-Cushing's with 100% sensitivity (CI, 88-100%) and specificity (CI, 71-100%). These data show that a simple index of total temporal variability (the intra-series CV) derived from the analysis of basal F profiles, provides a useful method to distinguish Cushing's disease from pseudo-Cushing's. A F or ACTH CV <40% discriminates Cushing's disease from pseudo-Cushing's and reflects reduced circadian and pulsatile variations.

Original languageEnglish (US)
Pages (from-to)791-799
Number of pages9
JournalJournal of Endocrinological Investigation
Volume25
Issue number9
DOIs
StatePublished - Oct 2002

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Pituitary ACTH Hypersecretion
Adrenocorticotropic Hormone
Confidence Intervals
Dexamethasone
Corticotropin-Releasing Hormone
Periodicity

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

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title = "Circadian variation in Cushing's disease and pseudo-Cushing states by analysis of F and ACTH pulsatility",
abstract = "Distinguishing pituitary-dependent Cushing's disease from pseudo-Cushing's states can present a diagnostic challenge. Although many studies potentially discriminate between the 2, only the dexamethasone-suppressed corticotropin-releasing hormone (CRF) stimulation test at 15 minutes is 100{\%} sensitive or specific. We measured baseline profiles of F and ACTH in 31 Cushing's disease patients, 11 with pseudo-Cushing's and 17 controls. Venous blood was collected at 30 minute intervals for 24-h. Subjects also had CRF stimulation tests and 2.0 mg/day dexamethasone suppression tests. F and ACTH profiles were analyzed for circadian rhythmicity, variability, and pulsatility. Relative circadian amplitude was decreased in Cushing's disease compared to both pseudo-Cushing's and normal states. Relative pulse amplitude was reduced in Cushing's disease. Because of this dampening of circadian and pulsatile variations, the overall variability of F and ACTH levels around their mean levels as quantified by the intra-series coefficient of variation (CV), was also decreased in Cushing's disease compared to pseudo-Cushing's and normal states. A F 24-h CV<40{\%} was able to distinguish Cushing's disease from pseudo-Cushing's with 100{\%} sensitivity (95{\%} confidence interval (CI), 88-100{\%}) and specificity (CI, 71-100{\%}). An ACTH CV<40{\%} had 97{\%} sensitivity (CI, 83-100{\%}) and 100{\%} specificity (CI, 71-100{\%}). An overnight 8-h F CV <40{\%} also distinguished Cushing's disease from pseudo-Cushing's with 100{\%} sensitivity (CI, 88-100{\%}) and specificity (CI, 71-100{\%}). These data show that a simple index of total temporal variability (the intra-series CV) derived from the analysis of basal F profiles, provides a useful method to distinguish Cushing's disease from pseudo-Cushing's. A F or ACTH CV <40{\%} discriminates Cushing's disease from pseudo-Cushing's and reflects reduced circadian and pulsatile variations.",
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Circadian variation in Cushing's disease and pseudo-Cushing states by analysis of F and ACTH pulsatility. / Cunningham, J. M.; Buxton, O. M.; Weiss, Roy E.

In: Journal of Endocrinological Investigation, Vol. 25, No. 9, 10.2002, p. 791-799.

Research output: Contribution to journalArticle

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