Cushing’s Disease
Open accessAbstract
In patients with Cushing’s disease (CD), prompt diagnosis and treatment are essential for favorable long-term outcomes, although this remains a challenging task. The differential diagnosis of CD is still difficult in some patients, even with an organized stepwise diagnostic approach. Moreover, despite the use of high-resolution magnetic resonance imaging (MRI) combined with advanced fine sequences, some tumors remain invisible. Surgery, using various surgical approaches for safe maximum tumor removal, still remains the first-line treatment for most patients with CD. Persistent or recurrent CD after unsuccessful surgery requires further treatment, including repeat surgery, medical therapy, radiotherapy, or sometimes, bilateral adrenalectomy. These treatments have their own advantages and disadvantages. However, the most important thing is that this complex disease should be managed by a multidisciplinary team with collaborating experts. In addition, a personalized and individual-based approach is paramount to achieve high success rates while minimizing the occurrence of adverse events and improving the patients’ quality of life. Finally, the recent new insights into the pathophysiology of CD at the molecular level are highly anticipated to lead to the introduction of more accurate diagnostic tests and efficacious therapies for this devastating disease in the near future.
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Most but not all patients with Cushing disease will have an increase in plasma ACTH by more than 50% and cortisol concentrations by more than 20% after CRH stimulation.
“Therefore, most but not all patients with Cushing disease will have an increase in plasma ACTH by more than 50% and cortisol concentrations by more than 20% after CRH stimulation.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [74]
Section 5.3.3 (CRH Test) says most patients with Cushing disease show an ACTH increase of more than 50% and/or a cortisol increase of more than 20%, while some may lack a response. The claim requires both increases in most patients; the passage does not establish that they occur together. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPatients with EAS are typically unresponsive to CRH, although some tumors, in particular bronchial carcinoids, can express CRH receptors.
“Patients with EAS are typically unresponsive although some tumors, in particular bronchial carcinoids can express CRH receptors (9, 74, 81, 82).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [74]
Section 5.3.3 (CRH Test; page not provided) says patients with ectopic ACTH syndrome are typically unresponsive to CRH. The passages do not support the additional claim that some tumors, particularly bronchial carcinoids, express CRH receptors. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIf a pituitary adenoma >6 mm is found on MRI, the need for further testing with BIPSS is not necessary.
“If a pituitary adenoma > 6 mm is found on MRI, the need for further testing with bilateral inferior petrosal sinus sampling (BIPSS) is not necessary (1, 9, 74, 75).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [74]
Section 5.4 says a tumor >6 mm on MRI can support a definitive diagnosis of Cushing’s disease when biochemical results are compatible. It recommends IPSS for inconclusive results, so MRI size alone does not establish that BIPSS is unnecessary. (LLM, conf=0.88)
Experimental — accuracy not yet measuredConventional MRI can only detect 36% to 63% of pituitary microadenomas in patients with Cushing disease.
“Compared with conventional MRI, which can only detect 36% to 63% of pituitary microadenomas in patients with Cushing disease, high-resolution 3T-MRI with 3-dimensional spoiled gradient-echo sequence is characterized by thinner sections and superior soft-tissue contrast and can detect adenomas as small as 2 mm (74).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [74]
High-resolution 3T-MRI with 3-dimensional spoiled gradient-echo sequence can detect pituitary adenomas as small as 2 mm.
“Compared with conventional MRI, which can only detect 36% to 63% of pituitary microadenomas in patients with Cushing disease, high-resolution 3T-MRI with 3-dimensional spoiled gradient-echo sequence is characterized by thinner sections and superior soft-tissue contrast and can detect adenomas as small as 2 mm (74).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [74]
The high-dose DST is most often negative in patients with EAS.
“The high-dose DST is most often negative in patients with EAS (74).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [74]
An absence of both ACTH and cortisol response is expected in patients with EAS, although false-positive results can be seen as EAS tumors may express type 3 vasopressin receptors.
“On the other hand, an absence of both ACTH and cortisol is expected in patients with EAS, although false-positive results can be seen as EAS tumors may express type 3 vasopressin receptors (9, 74, 81).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [74]
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References 318 · Cited by 65
Research works printed but not linked: 4
- [1]Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism) Obes. Res. 1932 2 486 508 10.1002/j.1550-8528.1994.tb00097.x 16353601 · DOI
- [42]Newell-Price J. Cushing disease The Pituitary 4th ed. Academic Press Cambridge, MA, USA 2017 515 571
- [303]Saeger W. Concerning the article “Cushing’s disease associated with both pituitary microadenoma and corticotroph hyperplasia” Exp. Clin. Endocrinol. Diabetes 2010 118 68 10.1055/s-0029-1243234 20127571 · DOI
- [310]Osamura R.Y. Grossman A. Korbonits M. Kovacs K. Lopes M.B.S. Matsuno A. Trouillas J. Pituitary adenoma WHO Classification of Tumours of Endocrine Organs 4th ed. Osamura R.Y. Klöppel G. Rosai J. IARC Press Lyon, France 2017 14 18
- Authors
- Nishioka, H., & Yamada, S.
- Affiliations
- Toranomon Hospital (JP)
- Okinaka Memorial Institute for Medical Research (JP)
- Corresponding author
- Yamada, Shozo
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2019-11-12
- Volume
- 8
- Issue
- 11
- Pages
- 1951
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC6912360
- OpenAlex
- W2988276690
- Cited by
- 65
- References
- 318
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 13 · 2021: 9 · 2020: 11 · 2019: 1
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- 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 › Epidemiology › Neuroendocrine Tumor Research Advances
- Keywords
- Cushing's disease, differential diagnosis, pituitary MRI, transsphenoidal surgery, adrenalectomy, medical therapy, radiotherapy, multidisciplinary management, personalized treatment, pathophysiology, quality of life
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