Cushing’s Syndrome: important issues in diagnosis and management
Abstract
Context: The diagnosis, differential diagnosis, and treatment of Cushing’s syndrome are challenging problems in clinical endocrinology. We focus on critical questions addressing screening for Cushing’s syndrome, differentiation of Cushing’s subtypes, and treatment options. Evidence Acquisition: Ovid’s MEDLINE (1996 through April 2006) was used to search the general literature. We also relied on previously published reviews and a recent monograph and cite a mix of primary articles and recent reviews. Evidence Synthesis: Although this article represents our opinion, it draws heavily on a recent consensus statement from experts in the field and a recent monograph on Cushing’s syndrome. Conclusions: We concluded that: 1) measurement of late-night or bedtime salivary cortisol is a useful approach to screen for Cushing’s syndrome; 2) measurement of suppressed plasma ACTH by immunometric assay is useful to differentiate ACTH-dependent and -independent Cushing’s syndrome; 3) inferior petrosal sinus sampling for ACTH should be performed in patients with ACTH-dependent hypercortisolism in whom a pituitary magnetic resonance imaging is normal or equivocal (in the absence of a pituitary ACTH gradient, prolactin levels should be measured to confirm the integrity of venous sampling); 4) computed tomography of the chest and abdomen and somatostatin receptor scintigraphy should be performed in patients with the occult ectopic ACTH syndrome; and 5) patients with Cushing’s disease should be referred to a neurosurgeon with extensive experience operating on corticotroph microadenomas. Bilateral laparoscopic adrenalectomy should be considered in patients with Cushing’s disease who fail therapies directed at the pituitary.
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Late-night salivary cortisol is a reliable, simple, and cost-effective first-line test for the diagnosis of Cushing syndrome.
“Late-night salivary cortisol (LNSC) is a reliable, simple, and cost-effective first-line test for the diagnosis of endogenous neoplastic hypercortisolism (CS) [15, 16, 34, 35, 42-52].”
From Prospective Evaluation of Late-Night Salivary Cortisol and Cortisone by EIA and LC-MS/MS in Suspected Cushing Syndrome (2020) · cites this paper as [42]
The screening discussion (p. 2) calls late-night salivary cortisol simple, reports sensitivity and specificity above 90–95%, and describes it as the most useful screening test. It says screening tests should have reasonable cost, but does not establish that this test is cost-effective. The paper also recommends additional tests for diagnostic confirmation when needed (pp. 2–3). (LLM, conf=0.84)
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References 89 · Cited by 294
- Authors
- Findling, J. W., & Raff, H.
- Affiliations
- Medical College of Wisconsin (US)
- Corresponding author
- Raff, Hershel
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2006-10-01
- Volume
- 91
- Issue
- 10
- Pages
- 3746-3753
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2168487042
- Cited by
- 294
- References
- 89
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 6 · 2023: 11 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 14 · 2018: 6 · 2017: 6 · 2016: 9 · 2015: 14 · 2014: 17 · 2013: 24 · 2012: 21
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- Cushing's syndrome, hypercortisolism, Cushing's disease, ectopic ACTH syndrome, ACTH-dependent Cushing's syndrome, ACTH-independent Cushing's syndrome, inferior petrosal sinus sampling, somatostatin receptor scintigraphy, prolactin, differential diagnosis, treatment options
- MeSH terms
- Adrenocorticotropic Hormone, Cushing Syndrome, Dexamethasone, Humans, Hydrocortisone, Pituitary Gland, Salivary Glands
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