Cited by 336Pituitary Gland Disorders and TreatmentsAdrenal and Paraganglionic TumorsAdrenal Hormones and Disorders

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Diagnosis and Management of Cushing’s Syndrome: Results of an Italian Multicentre Study 1

Invitti, Cecilia, Giraldi, Francesca Pecori, De Martin, Martina, Cavagnini, Francesco·1999·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jcem.84.2.5465

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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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Authors: Invitti, C., Giraldi, F. P., De Martin, M., & Cavagnini, F.
Affiliations: University of Milan (IT)
Corresponding author: Cavagnini, Francesco
ORCID: Invitti, Cecilia
Giraldi, Francesca Pecori
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
DOI: 10.1210/jcem.84.2.5465
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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Diagnosis and Management of Cushing’s Syndrome: Results of an Italian Multicentre Study 1

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