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Cited by 98Pituitary Gland Disorders and TreatmentsAdrenal Hormones and DisordersAdrenal and Paraganglionic Tumors

Differentiating between Cushing's disease and pseudo-Cushing's syndrome: comparison of four tests

Alwani, R A, Schmit Jongbloed, L W, de Jong, F H, van der Lely, A J, de Herder, W W, Feelders, R A·2014·European Journal of Endocrinology
DOI 10.1530/eje-13-0702
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Abstract

Objective: To evaluate the diagnostic performance of four different tests in order to differentiate between Cushing's disease (CD) and pseudo-Cushing's syndrome (PCS). Methods: In this prospective study, a total of 73 patients with clinical features of hypercortisolism and insufficient suppression of serum cortisol after 1 mg overnight dexamethasone and/or an elevated excretion of cortisol in 24-h urine samples were included. The circadian rhythm of serum cortisol levels as well as midnight serum cortisol (MserC) levels were assessed in all 73 patients. Late-night salivary cortisol (LNSC) concentrations were obtained in 44 patients. The dexamethasone–CRH (Dex–CRH) test was performed in 54 patients. Results: Fifty-three patients were diagnosed with CD and subsequently treated. Twenty patients were classified as having PSC. Serum cortisol circadian rhythm: the diurnal rhythmicity of cortisol secretion was retained in PCS. A cortisol midnight:morning ratio of >0.67 is highly suggestive of CD (positive predictive value (PPV) 100% and negative predictive value (NPV) 73%). MserC concentration >243 nmol/l has a PPV of 98% in predicting true CD (NPV 95%). LNSC level >9.3 nmol/l predicted CD in 94% of patients (NPV 100%). Dex–CRH test: after 2 days of dexamethasone suppression, a CRH-stimulated cortisol level >87 nmol/l ( T =15 min) resulted in a PPV of 100% and an NPV of 90%. Conclusion: The Dex–CRH test as well as a single measurement of cortisol in serum or saliva at late (mid-) night demonstrated high diagnostic accuracy in differentiating PCS from true CD.

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Crossref · 10.1530/eje-13-0702

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  • Over time, the effects of small increases in cortisol can lead to significant and longitudinal glucocorticoid exposure and can result in pathologic features of hypercortisolism.

    “Over time, the effects of small increases in cortisol can lead to significant and longitudinal glucocorticoid exposure and can result in pathologic features of hypercortisolism as is also illustrated in case 1 (1, 56, 57).”

    From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [57]

  • Hypercortisolism in pseudo-CS conditions is mainly mediated by activation of the HPA axis through neural pathways without tumorous hypercortisolemia.

    “Hypercortisolism in these conditions is mainly mediated by activation of the HPA axis through neural pathways without tumorous hypercortisolemia.”

    From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [57]

  • Pseudo-CS is nonneoplastic physiologic hypercortisolism that can occur in many medical disorders such as chronic alcoholism, chronic kidney disease, type 2 diabetes mellitus, and psychiatric conditions.

    “Pseudo-CS, or nonneoplastic physiologic hypercortisolism, is a phenomenon that can occur in many medical disorders such as chronic alcoholism, chronic kidney disease, type 2 diabetes mellitus, and psychiatric conditions.”

    From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [57]

  • There is decreased sensitivity to glucocorticoid negative feedback in the majority of pseudo-CS states, which may lead to mild increases in cortisol.

    “There is also decreased sensitivity to glucocorticoid negative feedback in the majority of these states which may lead to mild increases in cortisol.”

    From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [57]

  • If first-line tests show normal LNSC measurements and appropriate suppression of cortisol with DST, patients are unlikely to have neoplastic hypercortisolism.

    “if the first-line tests show normal LNSC measurements (57) and appropriate suppression of cortisol with DST, patients are unlikely to have neoplastic hypercortisolism.”

    From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [57]

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Authors
Alwani, R. A., Schmit Jongbloed, L. W., de Jong, F. H., van der Lely, A. J., de Herder, W. W., & Feelders, R. A.
Affiliations
Erasmus MC (NL)
Corresponding author
Alwani, R A
ORCID
Feelders, R A
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2014-04
Volume
170
Issue
4
Pages
477-486
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje-13-0702
OpenAlex
W2158086718
Cited by
98
References
47
Citations by year
2026: 10 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 10 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 1
FWCI
5.90
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (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
Cushing's disease, pseudo-Cushing's syndrome, hypercortisolism, late-night salivary cortisol, diagnostic accuracy, differential diagnosis
MeSH terms
Adenoma, Adult, Circadian Rhythm, Corticotropin-Releasing Hormone, Cushing Syndrome, Dexamethasone, Diagnosis, Differential, Female, Glucocorticoids, Humans, Hydrocortisone, Male, Middle Aged, Prospective Studies, Saliva, Sensitivity and Specificity, Pituitary ACTH Hypersecretion, ACTH-Secreting Pituitary Adenoma

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