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Cited by 21Adrenal Hormones and DisordersStress Responses and CortisolHormonal and reproductive studies

Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency

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Rousseau, Elise, Joubert, Michael, Trzepla, Géraldine, Parienti, Jean Jacques, Freret, Thomas, Vanthygem, Marie Christine, Desailloud, Rachel, Lefebvre, Hervé +3 more·2015·PLOS ONE
DOI 10.1371/journal.pone.0135975PMC PMC4552782
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Abstract

BACKGROUND: Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated. METHODS: Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients' cortisol AUC in the control range. RESULTS: Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement. CONCLUSIONS: Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone dose adjustment in AI patients.

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  • Patients in Rousseau et al. (2015) received HC doses distributed as 50%, 25%, and 25% across the day.

    “While patients in their study received HC doses distributed as 50%, 25%, and 25% across the day, the proposed model achieves the desired cortisol levels by administering doses of medication in a 60%, 20%, and 20% distribution.”

    From Model Predictive Controller to Regulate Cortisol Levels in Individuals With Adrenal Insufficiency (2026) · cites this paper as Rousseau et al. (2015)

  • These simulations are consistent with real patient data from Rousseau et al. (2015).

    “These simulations are consistent with real patient data from Rousseau et al. (2015).”

    From Model Predictive Controller to Regulate Cortisol Levels in Individuals With Adrenal Insufficiency (2026) · cites this paper as Rousseau et al. (2015)

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Research works printed but not linked: 2

  1. [5]Kraan GP, Dullart RP, Pratt JJ, Wolthers BG, Dtayer NM, De Bruin R. The daily cortisol production reinvestigated in healthy men. J Clin Endocrinol Metab. 1998; 83: 1247– 1252. 9543150
  2. [15]Pehuet-Figoni M, Bertagna X, Girard F, Bricaire H, Luton JP. How to interpret plasma ACTH level in treated Addisonian patients? Ann Endocrinol (Paris). 1989; 50: 54– 57. 2543260

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Authors
Rousseau, E., Joubert, M., Trzepla, G., Parienti, J. J., Freret, T., Vanthygem, M. C., Desailloud, R., Lefebvre, H., Coquerel, A., Reznik, Y., & PHAD Study Group
Affiliations
  • Centre Hospitalier Universitaire de Caen Normandie (FR)
  • Centre Hospitalier Universitaire Amiens-Picardie (FR)
Corresponding author
Reznik, Yves
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-08-28
Volume
10
Issue
8
Pages
e0135975
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0135975
PMC
PMC4552782
OpenAlex
W2130387888
Cited by
20
References
32
Citations by year
2024: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 3
FWCI
2.61
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Centre hospitalier régional universitaire de Lille
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
adrenal insufficiency, hydrocortisone replacement, serum cortisol, ACTH, dose-response relationship
MeSH terms
Adrenal Insufficiency, Adrenocorticotropic Hormone, Adult, Aged, Female, Humans, Hydrocortisone, Male, Middle Aged, Hormone Replacement Therapy

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