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Cited by 29Pituitary Gland Disorders and TreatmentsAdrenal Hormones and DisordersAdrenal and Paraganglionic Tumors

Hair cortisol and cortisone measurements for the diagnosis of overt and mild Cushing's syndrome

Brossaud, Julie, Charret, Léa, De Angeli, Delia, Haissaguerre, Magalie, Ferriere, Amandine, Puerto, Marie, Gatta-Cherifi, Blandine, Corcuff, Jean-Benoît +1 more·2021·European Journal of Endocrinology
DOI 10.1530/eje-20-1127
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Abstract

Objective: Hair cortisol (HF) and cortisone (HE) measurements reflect tissular exposure to cortisol over months and are increased in overt Cushing’s syndrome (CS). No data is available in mild CS. We compared the diagnostic performance of HF and HE between patients with overt or mild CS. Design: Single centre retrospective study. Methods: HF&HE were measured by LC-MS/MS in 48 consecutive adult females with Cushing’s disease (CD), ectopic ACTH syndrome, secreting adenomas and carcinomas, and adrenal incidentalomas. All had impaired dexamethasone suppression tests. Overt CS ( n = 25) was diagnosed in front of specific symptoms, a mean UFC (>1.5 ULN) and increased midnight serum cortisol or salivary cortisol. Mild CS ( n = 23) was diagnosed in patients lacking specific symptoms and displaying at least one additional biological abnormality including mildly increased UFC (≤1.5 ULN), increased midnight serum cortisol or salivary cortisol and suppressed plasma ACTH in patients with adrenal tumours. In this study, 84 healthy subjects and obese patients served as controls. Results: HF and HE showed roughly similar performance in overt CS (92 and 100% sensitivity, 91 and 99% specificity, respectively). HF and HE were lower in mild CS but higher than in controls ( P < 0.01). HE was correlated with midnight serum cortisol ( P < 0.02) and volume of adrenal incidentalomas ( P < 0.04) but not with UFC. HF and HE had 59% and 68% sensitivity, and 79 and 94% specificity, respectively, for the diagnosis of mild CS. Contrary to UFC, both HF and HE were in the range of overt CS in 11/23 patients with mild CS. Patients with mild CS and increased HE required more antihypertensive treatments and showed worser lipid profiles than patients with normal HE. Conclusions: HF and HE measurement performed better in overt than in mild CS but is a useful adjunct to diagnose mild CS and to identify adrenocortical incidentalomas responsible for excessive cortisol exposure.

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  • Hair cortisol and cortisone measurements can distinguish CS from controls.

    “Overall, hair cortisol and cortisone measurements can distinguish CS from controls, but substantial variability in reported cutoffs and diagnostic performance underscores the lack of validated thresholds and the need for further standardization before routine clinical use.”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [120]

  • Hair analysis can be performed at any time of the day in an outpatient setting.

    “Hair analysis (typically 3 cm closest to the scalp) provides a stable measure of cortisol, reducing false-positive results from acute stressors associated with serum, saliva, or urine testing, and it can be performed at any time of the day in an outpatient setting (120).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [120]

  • Hair analysis (typically 3 cm closest to the scalp) provides a stable measure of cortisol, reducing false-positive results from acute stressors associated with serum, saliva, or urine testing.

    “Hair analysis (typically 3 cm closest to the scalp) provides a stable measure of cortisol, reducing false-positive results from acute stressors associated with serum, saliva, or urine testing, and it can be performed at any time of the day in an outpatient setting (120).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [120]

  • Substantial variability in reported cutoffs and diagnostic performance of hair cortisol and cortisone underscores the lack of validated thresholds.

    “Overall, hair cortisol and cortisone measurements can distinguish CS from controls, but substantial variability in reported cutoffs and diagnostic performance underscores the lack of validated thresholds and the need for further standardization before routine clinical use.”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [120]

  • Studies evaluating hair cortisol and cortisone have reported diagnostic cutoffs ranging from approximately 5-31 pg/mg for hair cortisol and 14-28 pg/mg for hair cortisone, with sensitivities of ∼60-100% and specificities of ∼79-99%, depending on assay methodology, study population, and disease severity.

    “Studies evaluating hair cortisol and cortisone have reported diagnostic cutoffs ranging from approximately 5-31 pg/mg for hair cortisol and 14-28 pg/mg for hair cortisone, with sensitivities of ∼60-100% and specificities of ∼79-99%, depending on assay methodology, study population, and disease severity (Table 3) (119-121).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [120]

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Authors
Brossaud, J., Charret, L., De Angeli, D., Haissaguerre, M., Ferriere, A., Puerto, M., Gatta-Cherifi, B., Corcuff, J.-B., & Tabarin, A.
Affiliations
  • Université de Bordeaux (FR)
  • 4Department of Radiology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
  • 3Department of Endocrinology, Diabetes and Nutrition, CHU of Bordeaux and University of Bordeaux, France
Corresponding author
Tabarin, Antoine
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2021-03
Volume
184
Issue
3
Pages
445-454
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje-20-1127
OpenAlex
W3125813855
Cited by
29
References
0
Citations by year
2026: 7 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 2
FWCI
3.55
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
Keywords
hair cortisol, hair cortisone, Cushing's syndrome, Cushing's disease, ectopic ACTH syndrome, adrenal incidentaloma, urinary free cortisol, sensitivity and specificity, antihypertensive therapy, lipid profile
MeSH terms
ACTH Syndrome, Ectopic, Adenoma, Adrenal Gland Neoplasms, Adult, Aged, Cortisone, Cushing Syndrome, Diagnostic Techniques, Endocrine, Female, Hair, Humans, Hydrocortisone, Middle Aged, Predictive Value of Tests, Retrospective Studies, Sensitivity and Specificity, Severity of Illness Index, Case-Control Studies

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