Cushing's syndrome: Overview of clinical presentation, diagnostic tools and complications

ObjectiveThe European Registry on Cushing's syndrome (ERCUSYN) is designed to collect prospective and follow-up data at EU level on Cushing's syndrome (CS).Design and methodsBaseline data on 481 CS patients (390 females, 91 males; mean age (±s.d.): 44±14 years) collected from 36 centres in 23 countries, including new patients from 2008 and retrospective cases since 2000. Patients were divided into four major aetiologic groups: pituitary-dependent CS (PIT-CS) (66%), adrenal-dependent CS (ADR-CS) (27%), CS from an ectopic source (ECT-CS) (5%) and CS from other aetiologies (2%).ResultsProportion of men in the ECT-CS group was higher than in the other groups (P<0.05). The ADR-CS group was older than the PIT-CS (P<0.05). Prevalence of hirsutism (92%) and diabetes (74%) in ECT-CS was higher than in the other groups (P<0.05 and P<0.01 respectively). PIT-CS had more skin alterations, menstrual irregularities and hirsutism than ADR-CS (P<0.01). Reduced libido was more prevalent in men than women (P<0.01). Prevalence of spine osteoporosis was higher in men than women (P<0.05), and males had more vertebral and rib fractures than females (52 vs 18% for vertebrae; P<0.001 and 34 vs 23% for ribs; P<0.05). ECT-CS consulted a diabetologist more frequently than ADR-CS (P<0.05), while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS (P<0.05). Overall, weight gain was more common in women than men (P<0.01). CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups.ConclusionsThe ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level, depending on gender and aetiology.

Download Full-text

Diagnostic tests for Cushing's syndrome differ from published guidelines: data from ERCUSYN

Acta Endocrinologica ◽

10.1530/eje-16-0967 ◽

2017 ◽

Vol 176 (5) ◽

pp. 613-624 ◽

Cited By ~ 21

Author(s):

Elena Valassi ◽

Holger Franz ◽

Thierry Brue ◽

Richard A Feelders ◽

Romana Netea-Maier ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Diagnostic Tests ◽

Serum Cortisol ◽

Cushing's Syndrome ◽

Dexamethasone Suppression Test ◽

Diagnostic Tools ◽

Late Night ◽

Free Cortisol ◽

Suppression Test ◽

Dexamethasone Suppression

Objective To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing’s syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. Patients and methods We analyzed data on the diagnostic tests performed in 1341 patients with Cushing’s syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). Results Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05). Conclusions Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.

Download Full-text

Clinical Presentation and Diagnosis of Cushing’s Syndrome

Adrenal Disorders ◽

10.1007/978-1-59259-101-5_13 ◽

2001 ◽

pp. 179-191 ◽

Cited By ~ 1

Author(s):

Andrew N. Margioris ◽

George P. Chrousos

Keyword(s):

Cushing’S Syndrome ◽

Clinical Presentation ◽

Cushing's Syndrome

Download Full-text

Molecular derangements and the diagnosis of ACTH-Dependent Cushing’s syndrome

Endocrine Reviews ◽

10.1210/endrev/bnab046 ◽

2021 ◽

Author(s):

Lynnette K Nieman

Keyword(s):

Cushing’S Syndrome ◽

Clinical Presentation ◽

Pulmonary Thromboembolism ◽

Feedback Regulation ◽

Cushing's Syndrome ◽

Screening Tests ◽

Healthy Individuals ◽

Ectopic Acth ◽

Medical Treatments ◽

Clinical Presentations

Abstract Endogenous Cushing’s syndrome (CS) is associated with morbidities (diabetes, hypertension, clotting disorders ) and shortens life because of infections, pulmonary thromboembolism, and cardiovascular disease. Its clinical presentation is immensely variable, and diagnosis and treatment are often delayed. Thus, there are many opportunities for basic and clinical research leading to better tests, faster diagnosis, and optimized medical treatments. This review focusses on CS caused by excessive ACTH production. It describes current concepts of the regulation of ACTH synthesis and secretion by normal corticotropes, and mechanisms by which dysregulation occurs in corticotrope (termed “Cushing’s disease”) and non-corticotrope (so-called “ectopic”) ACTH-producing tumors. ACTH causes adrenal gland synthesis and pulsatile release of cortisol; the excess ACTH in these forms of CS leads to the hypercortisolism of endogenous CS. Again, the differences between healthy individuals and those with CS are highlighted. The clinical presentations and their use in the interpretation of CS screening tests are described. The tests used for screening and differential diagnosis of CS are presented, along with their relationship to cortisol dynamics, pathophysiology, and negative glucocorticoid feedback regulation in the two forms of ACTH-dependent CS. Finally, several gaps in current understanding are highlighted in the hope of stimulating additional research into this challenging disorder.

Download Full-text

Meningioma presenting with Cushing's syndrome: An unusual clinical presentation

Annals of Neurology ◽

10.1002/ana.10454 ◽

2002 ◽

Vol 53 (1) ◽

pp. 138-142 ◽

Cited By ~ 6

Author(s):

Francesca Pecori Giraldi ◽

Maria Rosa Terreni ◽

Claudia Andreotti ◽

Marco Losa ◽

Roberto Lanzi ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Clinical Presentation ◽

Cushing's Syndrome

Download Full-text

Neurodegenerative and inflammatory biomarkers in cerebrospinal fluid in patients with Cushing's syndrome in remission

Acta Endocrinologica ◽

10.1530/eje-13-0205 ◽

2013 ◽

Vol 169 (2) ◽

pp. 211-215 ◽

Cited By ~ 6

Author(s):

Oskar Ragnarsson ◽

Peter Berglund ◽

Derek N Eder ◽

Henrik Zetterberg ◽

Max A Hietala ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Cushing’S Syndrome ◽

Healthy Subjects ◽

Cushing's Syndrome ◽

Inflammatory Biomarkers ◽

Diagnostic Tools ◽

Csf Biomarkers ◽

Necrosis Factor Alpha ◽

Cross Sectional ◽

Monocyte Chemoattractant Protein 1

ObjectivePatients with Cushing's syndrome (CS) in long-term remission have impaired cognitive function. Cerebrospinal fluid (CSF) biomarkers are important diagnostic tools in the work-up of patients with cognitive impairment. The aim of this study was to analyze neurodegenerative and inflammatory biomarkers in the CSF of patients with CS in remission.DesignA cross-sectional, single-center study.PatientsTwelve women previously treated for CS and six healthy subjects.MeasurementsNeurodegenerative CSF markers: total tau, hyperphosphorylated tau, amyloid beta peptides, soluble amyloid precursor protein alpha and beta, neurofilament light proteins, glial fibrillary acidic protein, and monocyte chemoattractant protein 1; and inflammatory CSF markers: interferon gamma, interleukin (IL) 1B, IL2, IL4, IL5, IL8, IL10, IL12p70, IL13, and tumor necrosis factor alpha.ResultsThe mean age (mean±s.d.) was similar in patients with CS in remission (44.9±14 years) and healthy subjects (42.3±15.7 years;P=0.726). No differences were observed in the concentrations of any neurodegenerative biomarkers between the patients and healthy subjects. Nor were the concentrations of inflammatory biomarkers different between the groups.ConclusionsThe pattern of neurodegenerative and inflammatory biomarkers in the CSF of patients with CS in remission does not differ from that of the healthy subjects. The underlying mechanisms of the cognitive deficits in patients with CS in remission are different from those observed in patients with neurodegenerative disorders and remain to be explained.

Download Full-text