Metabolic changes in serum steroids for diagnosing and subtyping Cushing’s syndrome
Abstract
To evaluate the diagnostic value of serum levels of adrenal steroids for diagnosing and subtyping Cushing's syndrome. Patients diagnosed with endogenous Cushing's syndrome (34 and 19 patients with adrenal and pituitary Cushing's syndrome, respectively) and healthy controls (n = 34) were consecutively enrolled at Seoul National University from 2016 to 2020. Morning serum samples were collected before and 3 months after treatment. Serum steroids were profiled using liquid chromatography-mass spectrometry. The diagnostic value of each and the combination of steroids were assessed using the area under the curve of receiver operating characteristic (AUROC) and decision tree analysis. Tetrahydrocortisone and 6β-hydroxycortisol showed the highest AUROC (0.893 and 0.890, respectively) for the diagnosis of endogenous Cushing's syndrome. The decision tree composed of tetrahydrocortisone and 6β-hydroxycortisol correctly classified 79/87 (90.8 %) subjects. For subtyping into adrenal or pituitary Cushing's syndrome, dehydroepiandrosterone sulfate (DHEA-S) showed the highest AUROC (0.988), which was similar to that of plasma ACTH (0.994, P = 0.458). The decision tree composed of only DHEA-S correctly classified 51/53 (96.2 %) of the Cushing's syndrome subtype. DHEA-S showed a significant linear correlation with the plasma ACTH level, but not with the 24 -h urine free cortisol or dexamethasone suppression test results. All steroids, except allo-tetrahydrocortisol and tetrahydrocortisone, decreased significantly at 3 months post-treatment with similar patterns in both adrenal and pituitary Cushing's syndrome. Serum steroid profiling using a single morning serum sample provides valuable information for diagnosing and subtyping Cushing's syndrome.
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Corticotroph tumors are sensitive to CRH stimulation, and a substantial ACTH and cortisol increase (>50% of baseline) is compatible with a pituitary cause.
“Corticotroph tumors are sensitive to CRH stimulation and a substantial ACTH and cortisol increase (> 50% of baseline) are compatible with a pituitary cause (83, 84).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [83]
DHEAS secretion is partly ACTH driven, and low-normal or suppressed DHEAS levels point to an adrenal cause.
“DHEAS secretion is partly ACTH driven and low-normal or suppressed DHEAS levels point to an adrenal cause.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [83]
Measurement of DHEAS concentrations and a CRH test can be helpful to differentiate an adrenal from a pituitary cause of CS.
“Measurement of DHEAS concentrations and a CRH test can be helpful to differentiate an adrenal from a pituitary cause.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [83]
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Approach to the Patient: Diagnosis of Cushing Syndrome
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“Corticotroph tumors are sensitive to CRH stimulation and a substantial ACTH and cortisol increase (> 50% of baseline) are compatible with a pituitary cause (83, 84).”
BackgroundClinical and Technical Aspects in Free Cortisol Measurement
Choi, M.-H. (2022) · Endocrinology and Metabolism · doi:10.3803/enm.2022.1549 · Cited by 53 · see citing works
“steroids, including cortisol and its inactive metabolite cortisone [47,53-55,74-76].”
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“Serum steroid profiling Sample preparation was performed as described previously [9,16].”
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“Recently, Ahn et al. have shown that plasma DHEA is an as nearly good parameter as ACTH to differentiate between patients with adrenal and pituitary CS. 37 Furthermore, DHEA and ACTH-levels show a linear correlation.”
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“The established method reflects the clinical signatures of individual adrenal tumors of CS (5, 13, 22, 23), PA (5, 13,1 4)), and PPGL (11, 12, 14) characterized by excessive secretion of glucocorticoids, mineralocorticoids, and catecholamines, respectively.”
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Lateral Flow Immunoassay with a Concave Test Spot for the Determination of Cortisol in Human Serum
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“low cortisol levels in the body may lead to Cushing’s syndrome and Addison’s disease, respectively (Ahn et al. 2021).”
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“LC-MS has been used to subtype adrenal or pituitary Cushing’s syndrome by measuring dehydroepiandrosterone sulfate levels, especially when falsely elevated ACTH is suspected [36].”
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“Recently, a combination of machine-learning algorithms with mass spectrometry-based steroid profiling methods have been successfully introduced for differentiating adrenal diseases, including CAH, Cushing’s syndrome, and primary aldosteronism [12, 18, 19].”
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“Additional (34 – 36).”
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“…1.0 µg/L according to a ran - dom growth hormone (GH) measurement in patients with GH-secreting tumors in accordance with the most recent Acromegaly Consensus Conference guidelines, and the overnight dexamethasone suppression test was less than 1.8 µg/dL in patients with Cushing’s disease [ 24–28].”
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Development of colorimetric paper-based analytical device for cortisol detection
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“Unusual high and low cortisol levels in the body lead to Cushing’s syndrome and Addison’s disease, respectively [3].”
Background
- Authors
- Ahn, C. H., Lee, C., Shim, J., Kong, S. H., Kim, S.-J., Kim, Y. H., Lee, K. E., Shin, C. S., Kim, J. H., & Choi, M. H.
- Affiliations
- Seoul National University (KR)
- Korea University (KR)
- Corresponding author
- Kim, Jung Hee
- Choi, Man Ho
- ORCID
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 210
- Pages
- 105856
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W3135121179
- Cited by
- 21
- References
- 22
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 8 · 2022: 4 · 2021: 2
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Korea Institute of Science and Technology
- Seoul National University Hospital
- 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
- Cushing's syndrome, endogenous Cushing's syndrome, adrenal Cushing's syndrome, tetrahydrocortisone, 6β-hydroxycortisol, dehydroepiandrosterone sulfate, ACTH, diagnostic biomarkers, disease subtyping, liquid chromatography-mass spectrometry
- MeSH terms
- Adrenal Glands, Adult, Cushing Syndrome, Female, Humans, Hydrocortisone, Male, Middle Aged, Pituitary Gland, ROC Curve, Steroids, Tetrahydrocortisone, Case-Control Studies
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