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Time to diagnosis in Cushing's syndrome: a meta-analysis based on 5367 patients
Open accessAbstract
Context: Signs and symptoms of Cushing’s syndrome (CS) overlap with common diseases, such as the metabolic syndrome, obesity, osteoporosis, and depression. Therefore, it can take years to finally diagnose CS, although early diagnosis is important for prevention of complications. Objective: The aim of this study was to assess the time span between first symptoms and diagnosis of CS in different populations to identify factors associated with an early diagnosis. Data Sources: A systematic literature search via PubMed was performed to identify studies reporting on time to diagnosis in CS. In addition, unpublished data from patients of our tertiary care center and 4 other centers were included. Study Selection: Clinical studies reporting on the time to diagnosis of CS were eligible. Corresponding authors were contacted to obtain additional information relevant to the research question. Data Extraction: Data were extracted from the text of the retrieved articles and from additional information provided by authors contacted successfully. From initially 3326 screened studies 44 were included. Data Synthesis: Mean time to diagnosis for patients with CS was 34 months (ectopic CS: 14 months; adrenal CS: 30 months; and pituitary CS: 38 months; P < .001). No difference was found for gender, age (<18 and ≥18 years), and year of diagnosis (before and after 2000). Patients with pituitary CS had a longer time to diagnosis in Germany than elsewhere. Conclusions: Time to diagnosis differs for subtypes of CS but not for gender and age. Time to diagnosis remains to be long and requires to be improved.
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“These challenges often lead to delayed diagnosis, contributing to increased morbidity and mortality (48-50, 53).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [50]
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“The diagnosis of endogenous CS can be challenging due to overlap with common conditions, highly variable clinical features, and challenges in appropriately interpreting biochemical screening and diagnostic tests (11, 48-52).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [50]
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- Rubinstein, 2019. . : 10.5282//.153, Time to diagnosis in Cushing’s syndrome: a meta-analysis based on 5367 patients. · DOI
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BackgroundMethodSelf-citationToward a Diagnostic Score in Cushing's Syndrome
Braun, L., Riester, A., Osswald-Kopp, A., Fazel, J., Rubinstein, G., Bidlingmaier, M., Beuschlein, F., & Reincke, M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00766 · Cited by 90
“We have recently analyzed in a systematic meta-analysis of 45 studies on 5,560 patients with CS time to diagnosis and found that it has remained unchanged with a mean time of 34 months (10).”
MethodSelf-citation
Metadata
- Authors
- Rubinstein, G., Osswald, A., Hoster, E., Losa, M., Elenkova, A., Zacharieva, S., Machado, M. C., Hanzu, F. A., Zopp, S., Ritzel, K., Riester, A., Braun, L. T., Kreitschmann-Andermahr, I., Storr, H. L., Bansal, P., Barahona, M.-J., Cosaro, E., Dogansen, S. C., Johnston, P. C., Santos de Oliveira, R., Raftopoulos, C., Scaroni, C., Valassi, E., van der Werff, S. J. A., Schopohl, J., Beuschlein, F., & Reincke, M.
- Affiliations
- LMU Klinikum (DE)
- Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (DE)
- Vita-Salute San Raffaele University (IT)
- Medical University of Sofia (BG)
- Universidade de São Paulo (BR)
- Hospital Clínic de Barcelona (ES)
- Neurochirurgische Klinik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany
- Queen Mary University of London (GB)
- King Edward Memorial Hospital and Seth G.S. Medical College (IN)
- University Hospital Mútua de Terrassa (ES)
- University of Verona (IT)
- Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul, Turkey
- Royal Victoria Hospital (GB)
- Division of Pediatric Neurosurgery of the Department of Surgery and Anatomy, University Hospital of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- UCLouvain (BE)
- University of Padua (IT)
- Universitat Autònoma de Barcelona (ES)
- Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, München, Germany
- ORCID
- Rubinstein, German
- Osswald, Andrea
- Hoster, Eva
- Losa, Marco
- Elenkova, Atanaska
- Zacharieva, Sabina
- Machado, Márcio Carlos
- Hanzu, Felicia Alexandra
- Zopp, Stephanie
- Ritzel, Katrin
- Riester, Anna
- Braun, Leah Theresa
- Storr, Helen L
- Barahona, María-José
- Johnston, Philip C
- Raftopoulos, Christian
- Scaroni, Carla
- Valassi, Elena
- Schopohl, Jochen
- Beuschlein, Felix
- Reincke, Martin
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2019-10-29
- Volume
- 105
- Issue
- 3
- Pages
- e12-e22
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2949356757
- Semantic Scholar
- 76b4317201b4458ff9a1ddd19101a38655092f73
- Cited by
- 180
- References
- 66
- Citations by year
- 2026: 29 · 2025: 31 · 2024: 30 · 2023: 25 · 2022: 28 · 2021: 17 · 2020: 16 · 2019: 2
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.zora.uzh.ch
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion, other-oa)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Else Kröner-Fresenius Stiftung (2012_A103, 2015_A228)
- Deutsche Forschungsgemeinschaft (314061271-TRR 205)
- 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, time to diagnosis, delayed diagnosis, ectopic ACTH syndrome, adrenal Cushing's syndrome, early diagnosis
- MeSH terms
- Age Factors, Cushing Syndrome, Humans, Sex Factors, Time Factors, Early Diagnosis, Delayed Diagnosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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