The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Diagnosis and Management of Cushing’s Syndrome: Results of an Italian Multicentre Study 1
Abstract
The past 45 yr' experience with Cushing's syndrome (CS) has led to the awareness of its complex nature and, by the same token, brought about an increase in the diagnostic and therapeutic dilemmas. We carried out a retrospective multicentre study on the diagnostic work-up and treatment in 426 patients with CS, subdivided as follows: 288 with Cushing's disease (CD), 80 with an adrenal adenoma, 24 with an adrenal carcinoma, 25 with ectopic ACTH and/or CRH secretion, and 9 with ACTH-independent nodular adrenal hyperplasia. Normal urinary free cortisol (UFC) values among multiple collections were recorded in about 10% of patients with CS. In 28% of patients with ACTH-independent CS, basal ACTH concentrations were within the normal range but did not respond to CRH stimulation. Measurement of ACTH levels by immunoradiometric assay, rather than by RIA, offered a greater chance of recognizing patients with ACTH-independent CS or ectopic secretion. A 50% increase in ACTH or cortisol levels after CRH yielded a diagnostic accuracy of 86% and 61%, respectively, in the differential diagnosis of ACTH-dependent CS. An 80% decrease in cortisol levels after 8 mg dexamethasone overnight, or in UFC values after the classical 2-day administration, excluded an ectopic secretion but carried a low negative predictive value given the high number of nonsuppressors among patients with CD. Pituitary imaging identified an adenoma in 61% of patients with CD. At inferior petrosal sinus sampling, an ACTH centre: periphery gradient after CRH less than 3, correctly classified all patients with ectopic secretion but misdiagnosed 15% of 76 patients with CD. Transsphenoidal pituitary surgery, the standard therapy for CD, resulted in complete remission (appearance of clinical signs of adrenal insufficiency associated with low/normal UFC excretion and, when available, low/normal morning plasma ACTH and cortisol levels) in 69% of patients. The overall relapse rate after pituitary surgery was 17%. The probability of relapse-free survival, as assessed by Kaplan-Meier analysis, was 95% at 12 months, 84% at 2 yr, and 80% at 3 yr. Risk of relapse was significantly correlated with postoperative baseline plasma ACTH and cortisol peak after CRH. No relapses were observed among patients who did not respond to CRH. Other therapeutic approaches for CD, such as pituitary irradiation and medical therapy, resulted in normalization of cortisol secretion in about half of treated cases. In summary, an accurate selection of the available diagnostic tools leads to the correct diagnosis in the majority of patients with CS. The therapeutic options for CD, adrenal carcinoma, and ectopic secretion are, as yet, not fully satisfactory. The high incidence of relapse after pituitary surgery calls for a prolonged follow-up.
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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).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [84]
In the citing paper
“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 [84]
In the citing paper
“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 [84]
Citations
Cites
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Cushing's syndrome: a review of diagnostic tests.
Crapo, L. (1979) · Metabolism · doi:10.1016/0026-0495(79)90097-0 · Cited by 393
The Cushing Syndrome: An Update on Diagnostic Tests
Kaye, T. B., & Crapo, L. M. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-76-3-112-6-434 · Cited by 302
Ectopic Adrenocorticotropic Hormone Syndrome
WAJCHENBERG, B. L., Mendonca, B. B., Liberman, B., Pereira, M. A. A., Carneiro, P. C., Wakamatsu, A., & Kirschner, M. A. (1994) · Endocrine Reviews · doi:10.1210/edrv-15-6-752 · Cited by 272
Nieman, L. K., Oldfield, E. H., WESLEY, R. A., Chrousos, G. P., Loriaux, D. L., & Cutler, G. B. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.77.5.8077325 · Cited by 222
Repeat transsphenoidal surgery for Cushing's disease
Friedman, R., Oldfield, E. H., Nieman, L. K., Chrousos, G. P., Doppman, J. L., Cutler, G. B., & Loriaux, D. L. (1989) · Journal of neurosurgery · doi:10.3171/jns.1989.71.4.0520 · Cited by 211
Early repeat surgery for persistent Cushing's disease
Ram, Z., Nieman, L. K., Cutler, G. B., Chrousos, G. P., Doppman, J. L., & Oldfield, E. H. (1994) · Journal of neurosurgery · doi:10.3171/jns.1994.80.1.0037 · Cited by 195
Flack, M. R., Oldfield, E. H., Cutler, G. B., ZWEIG, M. H., Malley, J. D., Chrousos, G. P., Loriaux, D. L., & Nieman, L. K. (1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-116-3-211 · Cited by 161
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Dichek, H. L., Nieman, L. K., Oldfield, E. H., Pass, H. I., Malley, J. D., & Cutler, G. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.2.8106630 · Cited by 157
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The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline.
Nieman, L. K., Biller, B. M. K., Findling, J. W., Newell-Price, J., Savage, M. O., Stewart, P. M., & Montori, V. M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0125 · Cited by 2,718
“A widely cited normal response is a serum cortisol less than 5 g/dl ( 140 nmol/liter) (7, 80).”
BackgroundLacroix, A., Feelders, R. A., Stratakis, C. A., & Nieman, L. K. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61375-1 · Cited by 1,777
Diagnosis and complications of Cushing’s syndrome: a consensus statement
Arnaldi, G., Angeli, A., Atkinson, A. B., Bertagna, X., Cavagnini, F., Chrousos, G. P., Fava, G. A., Findling, J. W., Gaillard, R. C., Grossman, A. B., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030871 · Cited by 1,362
Self-citationIsidori, A. M., Kaltsas, G., Pozza, C., Frajese, V., Newell-Price, J. D. C., Reznek, R. H., Jenkins, P. J., Monson, J. P., Grossman, A. B., & BESSER, G. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1542 · Cited by 525
The Treatment of Cushing's Disease
Pivonello, R., Leo, M. D., Cozzolino, A., & Colao, A. A. L. (2015) · Endocrine Reviews · doi:10.1210/er.2013-1048 · Cited by 478
Metadata
- Authors
- Invitti, C., Giraldi, F. P., De Martin, M., & Cavagnini, F.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Cavagnini, Francesco
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1999-02
- Volume
- 84
- Issue
- 2
- Pages
- 440-448
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2795482603
- Cited by
- 336
- References
- 35
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 15 · 2021: 12 · 2020: 17 · 2019: 20 · 2018: 14 · 2017: 10 · 2016: 13 · 2015: 19 · 2014: 13 · 2013: 15 · 2012: 11
- FWCI
- 3.18
- 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, Cushing's disease, ectopic ACTH secretion, ACTH-independent Cushing's syndrome, adrenal adenoma, adrenocortical carcinoma, CRH stimulation test, ACTH measurement, dexamethasone suppression test, urinary free cortisol, inferior petrosal sinus sampling, transsphenoidal microsurgery, relapse, pituitary imaging, differential diagnosis
- MeSH terms
- Adenoma, Adolescent, Adrenal Gland Neoplasms, Adrenocorticotropic Hormone, Adult, Aged, Child, Child, Preschool, Corticotropin-Releasing Hormone, Cushing Syndrome, Diagnosis, Differential, Female, Humans, Hydrocortisone, Infant, Italy, Male, Middle Aged, Pituitary Neoplasms
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