A novel tool in the diagnosis and follow-up of (cyclic) Cushing's syndrome: measurement of long-term cortisol in scalp hair
Open accessAbstract
BACKGROUND: Measurement of cortisol in 24-h urine collections and midnight saliva are standard screening tests for Cushing's syndrome (CS). These tests reflect cortisol levels during a maximum of 24 h and do not provide historical information. Therefore, they can yield normal results in case of cyclic CS, which is a rare disorder that is characterized by alternating episodes of endogenous cortisol excess and normal cortisol secretion. The measurement of cortisol in scalp hair is a novel tool that might be helpful to establish the diagnosis of (cyclic) CS. Our aim was to study whether hair cortisol timelines correspond with clinical course in patients with CS and whether we could create retrospective timelines of cortisol exposure that correspond with symptomatic periods in patients suspected of cyclic CS. METHODS: Scalp hair was collected in 14 patients with confirmed CS and six patients suspected of cyclic CS. Cortisol was extracted from the hair samples with methanol, and an ELISA was used to measure cortisol levels in hair extracts. A group of 96 nonobese individuals were used as a control group. RESULTS: Hair cortisol levels were significantly elevated in CS patients (P<0.0001). Sensitivity and specificity of hair cortisol measurements for CS were 86 and 98%, respectively. Hair cortisol timelines of patients with CS and cyclic CS corresponded with clinical course. CONCLUSION: Hair samples can provide a historical timeline that corresponds with clinical course in patients with (cyclic) CS. This new diagnostic tool can contribute significantly to early recognition of patients suffering from cyclic CS.
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Hair cortisol and cortisone measurement may be useful in detecting cyclical or mild CS by reflecting cumulative cortisol levels over weeks to months.
“It may be useful in detecting cyclical or mild CS by reflecting cumulative cortisol levels over weeks to months, though further studies are needed to clarify its clinical utility.”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [117]
The Discussion reports that hair cortisol timelines reflected clinical course in cyclic Cushing’s syndrome and that a single hair sample can show cortisol exposure over previous months. The paper measures cortisol, not cortisone, and the cited passages do not establish usefulness for mild Cushing’s syndrome. The Discussion also calls for further refinement and standardization before clinical use. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHair cortisol and cortisone measurement is a non-invasive, emerging method of assessing long-term cortisol exposure.
“Hair cortisol and cortisone measurement offers a non-invasive, emerging method of assessing long-term cortisol exposure (117-119).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [117]
The Discussion (page unavailable) says a single hair sample can provide cortisol measurements reaching back months or years, and the Hair collection section describes obtaining it by cutting hair from the scalp. But the Hair analysis section measures cortisol only; it mentions cortisone solely as a substance with 3% assay cross-reactivity. This paper therefore supports the claim for hair cortisol, not hair cortisone measurement. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn a previous study with a set of cyclical CS patients, historical timelines using hair demonstrated dynamic cortisol concentrations over time corresponding with clinical cushingoid features.
“In our previous study with a set of cyclical CS patients, we created historical timelines using hair and indeed demonstrated dynamic cortisol concentrations over time corresponding with clinical cushingoid features (59).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [59]
Scalp hair cortisol analysis can be useful in studying the onset of CS (eg, in ectopic CS) or cyclic CS.
“Because hair can be used as a historical timeline, scalp hair cortisol analysis can also be useful in studying the onset of CS (eg, in ectopic CS) or cyclic CS (59, 68).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [59]
Hair steroid analysis has high diagnostic efficacy in screening of CS.
“We and others also showed high diagnostic efficacy in screening of CS with hair steroid analysis.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [59]
Scalp hair analysis is a patient-friendly noninvasive method yielding cortisol values representing long-term cortisol exposure of the past months.
“A relatively novel method of cortisol measurement in patients suspected of CS is scalp hair analysis, a patient-friendly noninvasive method yielding cortisol values representing long-term cortisol exposure of the past months (48, 59-62).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [59]
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References 14 · Cited by 122
- Authors
- Manenschijn, L., Koper, J. W., van den Akker, E. L. T., de Heide, L. J. M., Geerdink, E. A. M., de Jong, F. H., Feelders, R. A., & van Rossum, E. F. C.
- Affiliations
- Erasmus MC (NL)
- Radboud University Medical Center (NL)
- Corresponding author
- Manenschijn, L.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-10
- Volume
- 97
- Issue
- 10
- Pages
- E1836-E1843
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2043069086
- Semantic Scholar
- de2f6325ddeece1e5aba5c56eef28a834be89a53
- Cited by
- 122
- References
- 14
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 7 · 2020: 7 · 2019: 8 · 2018: 7 · 2017: 11 · 2016: 13 · 2015: 16 · 2014: 10 · 2013: 8 · 2012: 1
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Funders
- Erasmus Medisch Centrum
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- Cushing's syndrome, sensitivity and specificity, cortisol excess
- MeSH terms
- Adult, Aged, Methanol, Child, Cushing Syndrome, Diagnostic Techniques, Endocrine, Female, Follow-Up Studies, Hair, Humans, Hydrocortisone, Male, Middle Aged, Periodicity, Scalp, Sensitivity and Specificity, Solvents, Time Factors, Young Adult
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