Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry

Nora V. Esteban, Thérèse Loughlin, Alfred L. Yergey, Joanna K. Zawadzki, John D. Booth, Jorg C. Winterer, D. Lynn Loriaux

Research output: Contribution to journalArticle

359 Citations (Scopus)

Abstract

Growth retardation as well as the development of Cushingoid features in adrenally insufficient patients treated with the currently accepted replacement dose of cortisol (33-41 μmol/day·m2; 12-15 mg/m2·day) prompted us to reevaluate the cortisol production rate (FPR) in normal subjects and patients with Cushing's syndrome, using a recently developed thermospray liquid chromatography-mass spectrometry method. The stable isotope [9,12,12-2H3]cortisol was infused continuously for 31 h at about 5% of the anticipated FPR. Blood samples were obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer dilution in plasma was determined by liquid chromatography/mass spectrometry. The method was validated with controlled infusions in 6 patients with adrenal insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 ± 7.5 μmol/day (9.9 ± 2.7 mg/day) or 15.7 μmol/day · m2; 5.7 mg/m2 · day). A previously unreported circadian variation in FPR was observed. Patients with Cushing's syndrome demonstrated unequivocal elevation of FPR (84.7 ± 25.7 μmol/day) and loss of circadian rhythm. FPR and cortisol concentration correlated during each sample period in normal volunteers, indicating that cortisol secretion, rather than metabolism, is mainly responsible for changes in plasma cortisol. Our data suggest that the FPR in normal subjects may be lower than previously believed.

Original languageEnglish (US)
Pages (from-to)39-45
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume72
Issue number1
StatePublished - Jan 1991
Externally publishedYes

Fingerprint

Isotopes
Dilution
Mass spectrometry
Hydrocortisone
Mass Spectrometry
Cushing Syndrome
Liquid chromatography
Liquid Chromatography
Healthy Volunteers
Plasmas
Adrenal Insufficiency
Circadian Rhythm
Metabolism
Blood
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Esteban, N. V., Loughlin, T., Yergey, A. L., Zawadzki, J. K., Booth, J. D., Winterer, J. C., & Loriaux, D. L. (1991). Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. Journal of Clinical Endocrinology and Metabolism, 72(1), 39-45.

Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. / Esteban, Nora V.; Loughlin, Thérèse; Yergey, Alfred L.; Zawadzki, Joanna K.; Booth, John D.; Winterer, Jorg C.; Loriaux, D. Lynn.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 72, No. 1, 01.1991, p. 39-45.

Research output: Contribution to journalArticle

Esteban, NV, Loughlin, T, Yergey, AL, Zawadzki, JK, Booth, JD, Winterer, JC & Loriaux, DL 1991, 'Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry', Journal of Clinical Endocrinology and Metabolism, vol. 72, no. 1, pp. 39-45.
Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC et al. Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. Journal of Clinical Endocrinology and Metabolism. 1991 Jan;72(1):39-45.
Esteban, Nora V. ; Loughlin, Thérèse ; Yergey, Alfred L. ; Zawadzki, Joanna K. ; Booth, John D. ; Winterer, Jorg C. ; Loriaux, D. Lynn. / Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. In: Journal of Clinical Endocrinology and Metabolism. 1991 ; Vol. 72, No. 1. pp. 39-45.
@article{6a3026cb8b6b439ab17ab74c9aacd47e,
title = "Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry",
abstract = "Growth retardation as well as the development of Cushingoid features in adrenally insufficient patients treated with the currently accepted replacement dose of cortisol (33-41 μmol/day·m2; 12-15 mg/m2·day) prompted us to reevaluate the cortisol production rate (FPR) in normal subjects and patients with Cushing's syndrome, using a recently developed thermospray liquid chromatography-mass spectrometry method. The stable isotope [9,12,12-2H3]cortisol was infused continuously for 31 h at about 5{\%} of the anticipated FPR. Blood samples were obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer dilution in plasma was determined by liquid chromatography/mass spectrometry. The method was validated with controlled infusions in 6 patients with adrenal insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 ± 7.5 μmol/day (9.9 ± 2.7 mg/day) or 15.7 μmol/day · m2; 5.7 mg/m2 · day). A previously unreported circadian variation in FPR was observed. Patients with Cushing's syndrome demonstrated unequivocal elevation of FPR (84.7 ± 25.7 μmol/day) and loss of circadian rhythm. FPR and cortisol concentration correlated during each sample period in normal volunteers, indicating that cortisol secretion, rather than metabolism, is mainly responsible for changes in plasma cortisol. Our data suggest that the FPR in normal subjects may be lower than previously believed.",
author = "Esteban, {Nora V.} and Th{\'e}r{\`e}se Loughlin and Yergey, {Alfred L.} and Zawadzki, {Joanna K.} and Booth, {John D.} and Winterer, {Jorg C.} and Loriaux, {D. Lynn}",
year = "1991",
month = "1",
language = "English (US)",
volume = "72",
pages = "39--45",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry

AU - Esteban, Nora V.

AU - Loughlin, Thérèse

AU - Yergey, Alfred L.

AU - Zawadzki, Joanna K.

AU - Booth, John D.

AU - Winterer, Jorg C.

AU - Loriaux, D. Lynn

PY - 1991/1

Y1 - 1991/1

N2 - Growth retardation as well as the development of Cushingoid features in adrenally insufficient patients treated with the currently accepted replacement dose of cortisol (33-41 μmol/day·m2; 12-15 mg/m2·day) prompted us to reevaluate the cortisol production rate (FPR) in normal subjects and patients with Cushing's syndrome, using a recently developed thermospray liquid chromatography-mass spectrometry method. The stable isotope [9,12,12-2H3]cortisol was infused continuously for 31 h at about 5% of the anticipated FPR. Blood samples were obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer dilution in plasma was determined by liquid chromatography/mass spectrometry. The method was validated with controlled infusions in 6 patients with adrenal insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 ± 7.5 μmol/day (9.9 ± 2.7 mg/day) or 15.7 μmol/day · m2; 5.7 mg/m2 · day). A previously unreported circadian variation in FPR was observed. Patients with Cushing's syndrome demonstrated unequivocal elevation of FPR (84.7 ± 25.7 μmol/day) and loss of circadian rhythm. FPR and cortisol concentration correlated during each sample period in normal volunteers, indicating that cortisol secretion, rather than metabolism, is mainly responsible for changes in plasma cortisol. Our data suggest that the FPR in normal subjects may be lower than previously believed.

AB - Growth retardation as well as the development of Cushingoid features in adrenally insufficient patients treated with the currently accepted replacement dose of cortisol (33-41 μmol/day·m2; 12-15 mg/m2·day) prompted us to reevaluate the cortisol production rate (FPR) in normal subjects and patients with Cushing's syndrome, using a recently developed thermospray liquid chromatography-mass spectrometry method. The stable isotope [9,12,12-2H3]cortisol was infused continuously for 31 h at about 5% of the anticipated FPR. Blood samples were obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer dilution in plasma was determined by liquid chromatography/mass spectrometry. The method was validated with controlled infusions in 6 patients with adrenal insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 ± 7.5 μmol/day (9.9 ± 2.7 mg/day) or 15.7 μmol/day · m2; 5.7 mg/m2 · day). A previously unreported circadian variation in FPR was observed. Patients with Cushing's syndrome demonstrated unequivocal elevation of FPR (84.7 ± 25.7 μmol/day) and loss of circadian rhythm. FPR and cortisol concentration correlated during each sample period in normal volunteers, indicating that cortisol secretion, rather than metabolism, is mainly responsible for changes in plasma cortisol. Our data suggest that the FPR in normal subjects may be lower than previously believed.

UR - http://www.scopus.com/inward/record.url?scp=0026096434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026096434&partnerID=8YFLogxK

M3 - Article

VL - 72

SP - 39

EP - 45

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -