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 In addition, unpublished data from patients of our tertiary care center and 4 other centers were included.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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Challenges in diagnosing CS often lead to delayed diagnosis, contributing to increased morbidity and mortality.
“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]
The paper says that overlapping symptoms can delay CS diagnosis, and its Discussion reports a mean time to diagnosis of 34 months. It also says that the duration of hypercortisolism appears to be an important determinant of morbidity and premature mortality. However, it does not directly establish that the diagnostic delays it measured increased those outcomes; the claim presents that link more definitively than the paper does. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe 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.
“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]
The introduction says CS symptoms overlap with other conditions and can delay diagnosis. The Discussion describes unusual and progressive presentations and says current biochemical screening tests have significant sensitivity and specificity issues (p. 22). These passages support diagnostic difficulty, but do not specifically address challenges in interpreting screening or diagnostic test results. (LLM, conf=0.82)
Experimental — accuracy not yet measured
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“By contrast, a meta-analysis of global studies including 5,387 patients suggested a shorter time frame (mean 34 months, 95% CI 30–38 months) 109 .”
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“Cushing syndrome (CS) is a rare condition (1) that is often diagnosed late in the course of disease, often years after the first onset of symptoms (2).”
Self-citationAcute and Life-threatening Complications in Cushing Syndrome: Prevalence, Predictors, and Mortality
Schernthaner-Reiter, M. H., Siess, C., Micko, A. S. G., Zauner, C., Wolfsberger, S., Scheuba, C., Riss, P., Knosp, E., Kautzky‐Willer, A., Luger, A., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab058 · Cited by 55 · see citing works
Fallo, F., Dalmazi, G. D., Beuschlein, F., Biermasz, N. R., Castinetti, F., Elenkova, A. P., Faßnacht, M., Isidori, A. M., Kaštelan, D., Korbonits, M., et al. (2022) · Journal of Hypertension · doi:10.1097/hjh.0000000000003252 · Cited by 48 · see citing works
“Indeed, ‘cured’ Cushing’s syndrome patients show sustained systemic problems, including an impaired quality of life [16], the severity of which is associated with the length of prior exposure to glucocorticoid excess, often reflected by a delay in diagnosis of at least 2–3 years [16,17].”
BackgroundSelf-citationDiagnostic workup of Cushing’s syndrome
Balomenaki, M., Margaritopoulos, D., Vassiliadi, D. A., & Tsagarakis, S. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13111 · Cited by 41 · see citing works
Molecular Derangements and the Diagnosis of ACTH-Dependent Cushing’s Syndrome
Nieman, L. K. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab046 · Cited by 33 · see citing works
“This is best understood in the context of the correct ways to achieve a complete 24-h collection: (1) The patient wakes up and discards the first voided urine; all subsequent voids are collected until waking at the same time the next day, at which time the waking void is collected, or (2) the collection is started at…”
BackgroundInfluentialQuality of life in Cushing's syndrome.
Bride, M., Crespo, I., Webb, S., & Valassi, E. (2021) · Best practice & research. Clinical endocrinology & metabolism · doi:10.1016/j.beem.2021.101505 · Cited by 19 · see citing works
Self-citationHidden hypercortisolism: a too frequently neglected clinical condition
Giovanelli, L., Aresta, C., Favero, V., Bonomi, M., Cangiano, B., Eller-Vainicher, C., Grassi, G., Morelli, V., Pugliese, F., Falchetti, A., et al. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01484-2 · Cited by 32 · see citing works
Bengtsson, D., Ragnarsson, O., Berinder, K., Dahlqvist, P., Engström, B. E., Ekman, B., Höybye, C., Burman, P., & Wahlberg, J. (2021) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/clinem/dgab079 · Cited by 18 · see citing works
“≥ 1 psychotropic drug 44 (34) 91 (18) 2.”
BackgroundMondin, A., Ceccato, F., Voltan, G., Mazzeo, P., Manara, R., Denaro, L., Scaroni, C., & Barbot, M. (2023) · Pituitary · doi:10.1007/s11102-023-01343-2 · Cited by 23 · see citing works
“Regarding complications, as there is usually a delay in CD diagnosis [25], Kaplan Meier curves for event free probability were calculated beginning 24 months prior to the diagnosis in order to include “prior” events possibly related to cortisol excess in our analysis.”
MethodSelf-citationCirculating microRNA Expression in Cushing’s Syndrome
Vetrivel, S., Zhang, R., Engel, M., Altieri, B., Braun, L., Oßwald, A., Bidlingmaier, M., Faßnacht, M., Beuschlein, F., Reincke, M., et al. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.620012 · Cited by 27 · see citing works
Self-citationTan, Y., Feng, J., Xiao, Y. M., & Bao, C. (2022) · Journal of Materials Chemistry B · doi:10.1039/d2tb00484d · Cited by 29 · see citing works
Liu, T., Yu, H., Wang, S., Li, H., Du, X., & He, X. (2023) · Nutrition & Metabolism · doi:10.1186/s12986-023-00726-3 · Cited by 25 · see citing works
“Moreover, the signs and symptoms of Cushing’s syndrome caused by glucocorticoids have a range of systemic and local effects on bone and mineral metabolism that overlap with common diseases, such as metabolic syndrome, obesity, and osteoporosis [68].”
BackgroundCharacteristics and outcomes of the Finnish ectopic ACTH syndrome cohort
Toivanen, S., Leijon, H., Arola, A., Soinio, M., Hämäläinen, P., Metso, S., Knutar, O., Koivikko, M. L., Ebeling, T., Moilanen, L., et al. (2021) · Endocrine · doi:10.1007/s12020-021-02768-0 · Cited by 25 · see citing works
“In our study, SCLC was diagnosed in 15% of cases, in line with previous reports.”
BackgroundMethodInfluentialMusculoskeletal complications of Cushing syndrome
Leszczyńska, D., Szatko, A., Papierska, L., Zgliczyński, W., & Glinicki, P. (2023) · Reumatologia/Rheumatology · doi:10.5114/reum/169889 · Cited by 57 · see citing works
Zdrojowy-Wełna, A., Stachowska, B., & Bolanowski, M. (2024) · Pituitary · doi:10.1007/s11102-024-01427-7 · Cited by 21 · see citing works
“The average time to diagnosis of Cushing’s disease (CD) is 38 months [1].”
Endogenous Cushing's syndrome and cancer risk
Rudman, Y., Fleseriu, M., Dery, L., Masri‐Iraqi, H., Sasson, L., Shochat, T., Kushnir, S., Shimon, I., & Akirov, A. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae098 · Cited by 19 · see citing works
Ferrière, A., & Tabarin, A. (2021) · La Presse Médicale · doi:10.1016/j.lpm.2021.104091 · Cited by 19 · see citing works
The Socioeconomic Consequences of Cushing’s Syndrome: A Nationwide Cohort Study
Ebbehøj, A. L., Søndergaard, E., Jepsen, P., Stochholm, K., Svane, H. M. L., Madsen, M., Poulsen, P. L., & Jørgensen, J. O. L. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac174 · Cited by 19 · see citing works
Unmet needs in Cushing’s syndrome: the patients’ perspective
Valassi, E., Chiodini, I., Feelders, R. A., Andela, C. D., Abou-Hanna, M., Idres, S., & Tabarin, A. (2022) · Endocrine Connections · doi:10.1530/ec-22-0027 · Cited by 18 · see citing works
Self-citationClinical Spectrum of USP8 Pathogenic Variants in Cushing's Disease
Rebollar‐Vega, R., Zuarth-Vázquez, J. M., & Hernández-Ramírez, L. C. (2023) · Archives of Medical Research · doi:10.1016/j.arcmed.2023.102899 · Cited by 16 · see citing works
Akirov, A., Fleseriu, M., Masri‐Iraqi, H., Shochat, T., Kushnir, S., Shimon, I., & Rudman, Y. (2025) · European Journal of Endocrinology · doi:10.1093/ejendo/lvaf059 · Cited by 15 · see citing works
Face-based machine learning diagnostics: applications, challenges and opportunities
Song, J., He, M., Zheng, X., Zhang, Y., Bi, C., Feng, J., Du, J., Li, H., & Shen, B. (2025) · Artificial Intelligence Review · doi:10.1007/s10462-025-11246-2 · Cited by 15 · see citing works
Braun, L. T., Vogel, F., Nowak, E., Rubinstein, G., Zopp, S., Ritzel, K., Beuschlein, F., & Reincke, M. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae127 · Cited by 15 · see citing works
Self-citationGuo, Y. C., Li, M., Liu, X., Duo, H., Huang, B., Lu, H., Zhang, X., Li, X., Zhao, Y., Lian, K., et al. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.04.002 · Cited by 16 · see citing works
Animal Models of Cushing's Syndrome
Nishiyama, M., Iwasaki, Y., & Makino, S. (2022) · Endocrinology · doi:10.1210/endocr/bqac173 · Cited by 15 · see citing works
Kishlyansky, D., Leung, A. A. C., Pasieka, J. L., Mahajan, A., & Kline, G. A. (2024) · Endocrine Related Cancer · doi:10.1530/erc-24-0029 · Cited by 14 · see citing works
Pituitary tumor centers of excellence for Cushing’s disease
Couselo, M., Frara, S., Giustina, A., & Casanueva, F. F. (2022) · Pituitary · doi:10.1007/s11102-022-01264-6 · Cited by 14 · see citing works
Stachowska, B., Kuliczkowska-Płaksej, J., Kałużny, M., Grzegrzółka, J., Jończyk, M., & Bolanowski, M. (2020) · Endocrine · doi:10.1007/s12020-020-02468-1 · Cited by 13 · see citing works
Bedtime Salivary Cortisol as a Screening Test for Cushing Syndrome in Children
Ueland, G. Å., Kellmann, R., Jørstad Davidsen, M., Viste, K., Husebye, E. S., Almås, B., Storr, H. L., Sagen, J. V., Mellgren, G., Júlíusson, P. B., et al. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab033 · Cited by 12 · see citing works
“Delayed diagnosis is a recognized problem [24], and it is suspected that several children with CS actually have had this condition from childhood, but remain undiagnosed until adulthood.”
BackgroundSelf-citationBlew, K., Mater, D. V., & PAGE, L. C. (2023) · JCEM Case Reports · doi:10.1210/jcemcr/luad101 · Cited by 13 · see citing works
“Delayed diagnosis is common in ectopic ACTH secretion causing CS, with a mean time to diagnosis of 14 months [5].”
BackgroundWhite blood cell count: a valuable tool for suspecting Cushing’s syndrome
Paja, M., Merlo, I., Rodríguez-Soto, J., Cruz-Iglesias, E., Moure, M., Elias, C., Oleaga, A., & Egaña, N. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01892-6 · Cited by 10 · see citing works
The Interdisciplinary Management of Newly Diagnosed Pituitary Tumors
Jaursch-Hancke, C., Deutschbein, T., Knappe, U. J., Saeger, W., Flitsch, J., & Faßnacht, M. (2021) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.m2021.0015 · Cited by 12 · see citing works
Neuropsychological functioning in patients with Cushing’s disease and Cushing’s syndrome
Siegel, S., Kirstein, C. F., Grzywotz, A., Hütter, B. O., Wrede, K. H., Kuhna, V., & Kreitschmann-Andermahr, I. (2021) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-1247-4651 · Cited by 10 · see citing works
Self-citationLack of sensitivity of diagnostic Cushing-scores in Germany: a multicenter validation
Braun, L., Vogel, F., Rubinstein, G., Zopp, S., Nowak, E., Constantinescu, G. A., Masjkur, J. R., Detomas, M., Pamporaki, C., Altieri, B., et al. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvac016 · Cited by 10 · see citing works
Self-citationSun, H., Wu, C., Hu, B., & Xie, G. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2282183 · Cited by 9 · see citing works
“…contributing to the maintenance of comorbidities, poor Qol and short life expectancy, even after long-term clearance of excess hormone levels [20,21]. in our study, individuals with VFs exhibited a 1.5-fold longer median presumed disease duration than those without VFs. although not…”
BackgroundInfluentialUpdate on Medical Treatment of Cushing’s Syndrome
Dillon, B. R., Agrawal, N., Schwarz, Y., Dancel-Manning, K., Tabarin, A., Lacroix, A., Hofland, L. J., & Feelders, R. A. (2025) · Drugs · doi:10.1007/s40265-025-02223-8 · Cited by 9 · see citing works
“…ti ng do s e s ( 1500 – 2500 m g d a il y ) h a v e b ee n u s e d i n t h e t r ea t m e n t o f i n t e n s e hyp e r c o r ti s o li s m [ 54 , 6 4 , 65 ] 45– 100 % r e m i ss i on r a t e s i n C D r e po r t e d w it h m ea n 71 % [ 56 ] , 66 % c on t r o l i n a m e t a - a n a l y s i s […”
Consumption of Health Functional Foods according to Age Group in Some Regions of Korea
Chung, H. K., & Lee, H. (2011) · Journal of the Korean Dietetic Association · Cited by 9 · see citing works
Nowak, E., Vogel, F., Braun, L., Zopp, S., Rubinstein, G., Schilbach, K., Bidlingmaier, M., Zimmermann, P., Thorsteinsdottir, J., Schweizer, J. R. D. O. L., et al. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae097 · Cited by 8 · see citing works
Self-citationEvaluations of secondary hypertension and laboratory data in the elderly population
Chen, Z., Chan, C., Lin, C.-H., Lee, C.-F., Lo, H.-Y., Huang, Y., Yeh, C., Chen, M. Y., Lai, T., Huang, K., et al. (2024) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2024.07.020 · Cited by 8 · see citing works
Cushing syndrome in paediatric population: who and how to screen
Chioma, L., Patti, G., Cappa, M., & Maghnie, M. (2024) · Journal of Endocrinological Investigation · doi:10.1007/s40618-024-02452-w · Cited by 7 · see citing works
Impact of remission status in endogenous Cushing's syndrome on cancer incidence
Rudman, Y., Fleseriu, M., Masri‐Iraqi, H., Shochat, T., Kushnir, S., Shimon, I., & Akirov, A. (2025) · European Journal of Endocrinology · doi:10.1093/ejendo/lvaf028 · Cited by 7 · see citing works
Effects of metyrapone in patients with mild hypercortisolism
Musolino, A., Favero, V., Parazzoli, C., Aresta, C., Testa, S., Persani, L., Corbetta, S., Chiodini, I., & Morelli, V. (2025) · European Journal of Endocrinology · doi:10.1093/ejendo/lvaf216 · Cited by 7 · see citing works
Nowotny, H. F., Seiter, T. M., Ju, J., Gottschlich, A., Schneider, H., Zopp, S., Vogel, F., Tschaidse, L., Auer, M. K., Lottspeich, C., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1275828 · Cited by 7 · see citing works
“…fi ciency (PAI) with either an inborn lack of cortisol but maintained adrenal androgen synthesis in congenital adrenal hyperplasia (CAH) versus complete loss of adrenal function over time due to an autoimmune disorder in Addison ’ s disease (AD) or abruptly due to bilateral adrenalectomy (1, 2).”
BackgroundSelf-citationThyroid function spectrum in Cushing’s syndrome
Yu, P., Yuan, H., Chen, H., & Li, X. (2024) · BMC Endocrine Disorders · doi:10.1186/s12902-024-01614-4 · Cited by 7 · see citing works
“We performed this analysis as previously reported [8].”
MethodCanat, M. M. (2023) · SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital · doi:10.14744/semb.2023.14306 · Cited by 7 · see citing works
“[21] This delay is due to both the non-specificity of hypercortisolism symptoms/ signs and the complexity of screening tests (UFC, late-night salivary and serum cortisol, and low-dose DSTs).”
BackgroundMasri‐Iraqi, H., Rudman, Y., Shochat, T., Kushnir, S., Shimon, I., Fleseriu, M., & Akirov, A. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02535-2 · Cited by 7 · see citing works
“The time to diagnosis in both adrenal CS and CD often exceeds 30 months, typically based on clinical suspicion or patient-reported symptoms [36].”
Cushing Syndrome due to a Pancreatic Neuroendocrine Tumor Treated With Radiofrequency Ablation
Sideri, A., Fang, J., Visrodia, K., & Page‐Wilson, G. (2023) · JCEM Case Reports · doi:10.1210/jcemcr/luad022 · Cited by 6 · see citing works
“…adrenocorticotropic hormone (ACTH)-dependent, arising from corticotroph pituitary adenomas (Cushing disease), and less frequently from ectopic neuroendocrine tumors including thymic, pancreatic, and bronchial carcinoids; pheochromocytomas; and medullary thyroid and small cell lung carcinomas [1].”
BackgroundDery, L., Stern, J., Shimon, I., Rudman, Y., Kushnir, S., Shochat, T., Fleseriu, M., & Akirov, A. (2024) · Pituitary · doi:10.1007/s11102-024-01399-8 · Cited by 6 · see citing works
“This aligns with a meta-analysis that has identified a shorter time to diagnose aCS compared to CD, although the result was not significant [34].”
Biochemical Control in Cushing's Syndrome: Outcomes of the Treatment in a Large Single Center Cohort
Ritzel, K., Fazel, J., August, L., Fedtke, V., Nowak, E., Vogel, F., Braun, L., Zopp, S., Then, C., Kunzel, H. E., et al. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae337 · Cited by 6 · see citing works
Self-citationScreening of hypercortisolism among patients with hypertension: an Italian nationwide survey
Dalmazi, G. D., Goi, J., Burrello, J., Tucci, L., Cicero, A. F. G., Mancusi, C., Moia, E. C., Iaccarino, G., Borghi, C., Muiesan, M. L., et al. (2024) · Journal of Endocrinological Investigation · doi:10.1007/s40618-024-02387-2 · Cited by 6 · see citing works
An Update on the Genetic Drivers of Corticotroph Tumorigenesis
Hernández-Ramírez, L. C., Perez‐Rivas, L. G., Theodoropoulou, M., & Korbonits, M. (2024) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-2337-2265 · Cited by 6 · see citing works
“The untreated CD is associated with higher morbidity and mortality, and therefore, timely diagnosis and efficient treatment are critical [2–5]; diagnosis is delayed by an average of 3.2 years [6].”
BackgroundInfluentialPatient reported outcomes and treatment satisfaction in patients with cushing syndrome
Rakovec, M., Zhu, W., Khalafallah, A. M., Salvatori, R., Hamrahian, A., Gallia, G., Ishii, M., London, N., Ramanathan, M., Rowan, N., et al. (2022) · Endocrine · doi:10.1007/s12020-022-03214-5 · Cited by 4 · see citing works
“reported a mean overall time to diagnosis of 34 months (95% confidence interval 30–38) [30].”
BackgroundCushing's Syndrome in the Elderly
Zdrojowy-Wełna, A., & Valassi, E. (2024) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-2317-8821 · Cited by 7 · see citing works
“In particular, CS may be misdiagnosed with metabolic syndrome, especially in the first phas - es of the disease, leading to a mean delay in diagnosis of about three years, also influenced by the rarity of the condition (estimat - ed incidence 0.2–5/1000 000 per year) [3, 4].”
BackgroundInfluentialSelf-citationObesity care in Chinese adults: from evidence to clinical practice
An, J., Jia, Q., Huang, Y., Cao, Y., Duan, Y., Zhang, H., & Li, S. (2025) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbaf036 · Cited by 8 · see citing works
“For example, the median time to initial diagnosis of Cushing syndrome is 34 months from the symptom onset [ 33 ].”
Plutzky, J., Taub, P. R., Bhatt, D. L., Dhaybi, O. A., Aroda, V. R., BASILE, J. N., Bloch, M. J., Budoff, M. J., Busch, R. S., Buse, J. B., et al. (2026) · JACC Advances · doi:10.1016/j.jacadv.2026.102596 · Cited by 5 · see citing works
The molecular genetics of adrenal cushing
Vaduva, P., & Bertherat, J. Y. (2024) · HORMONES · doi:10.1007/s42000-024-00608-0 · Cited by 5 · see citing works
“Mortality is also high in adrenocortical carcinoma, but mainly due to tumor growth and metastasis [9].”
Socio-Economic Consequences of Cushing's Syndrome: A Nationwide Cohort StudyPreprint
Ebbehøj, A. L., Søndergaard, E., Jepsen, P., Stochholm, K., Svane, H. M. L., Madsen, M., Poulsen, P. L., & Jørgensen, J. O. L. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4000566 · Cited by 5 · see citing works
Changes in clinical features of adrenal Cushing syndrome: a national registry study
Katabami, T., Asai, S., Matsuba, R., Sone, M., Izawa, S., Ichijo, T., Tsuiki, M., Okamura, S., Yoshimoto, T., Otsuki, M., et al. (2025) · Endocrine Connections · doi:10.1530/ec-24-0684 · Cited by 4 · see citing works
“However, in most studies from other countries, adrenal CS accounts for a smaller proportion of all CS cases compared to Japan (20 – 47 vs >50%, respectively), despite a rise in incidence in recent reports (10, 13, 14, 15, 16).”
Clinical Practice Patterns in Bone Health Assessment and Management in Endogenous Cushing's Syndrome
Behary, P., Raveendran, D., Nair, R., Marco, A. D., Papadopoulou, D. A., Wernig, F., Abbara, A., Meeran, K. M., Martin, N. M., Cox, J., et al. (2025) · Clinical Endocrinology · doi:10.1111/cen.70085 · Cited by 4 · see citing works
Resistant hypertension, hyperaldosteronism, and the emerging understanding of hypercortisolism
EINHORN, D. F., Mende, C. W., & Auchus, R. J. (2026) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000001315 · Cited by 4 · see citing works
Hepşen, S., Gul, U., Bostan, H., Akhanlı, P., Sencar, M. E., Kızılgül, M., Ünsal, İ. Ö., & Çakal, E. (2024) · International Journal of Obesity · doi:10.1038/s41366-024-01598-0 · Cited by 4 · see citing works
“Frequently, the diagnosis of this condition is delayed until clinical signs and symptoms become more pronounced, often resulting in the emergence of signi fi cant comorbidities by that time [2].”
BackgroundThe Evolution of Our Understanding of the Nuances of Pathologic Cortisol Secretion
Blevins, L. S. (2025) · Endocrine Practice · doi:10.1016/j.eprac.2025.06.002 · Cited by 4 · see citing works
Cushing Mortality in Remission: Not Out of the Woods
Kelsall, A., & Newell-Price, J. D. C. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac341 · Cited by 4 · see citing works
“On the other hand, against this notion is that the time to diagnosis for patients with adrenal Cushing appears to be significantly less than those with pituitary disease (30 months vs 38 months) (8).”
BackgroundLam-Chung, C., & Ramos, D. C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1075785 · Cited by 4 · see citing works
“Moreover, the time taken to diagnose CS differs according to its subtypes and geographic regions (27).”
BackgroundMethodInfluentialGutiérrez, C. G., Saavedra-Vasquez, M. A., Corrales, E. P., Berrocal, V. R., Luque‐Ramírez, M., & Castro, M. A. (2025) · Annales d Endocrinologie · doi:10.1016/j.ando.2025.101802 · Cited by 3 · see citing works
Venous thromboembolism in patients with pituitary adenoma: UK multicentre cohort study
Isand, K., Pofi, R., Härmson, O., Vergis, M., Mahendran, H., Ayuk, J., Wass, J. A. H., Yajnik, P., Bradley, K., Karavitaki, N., et al. (2025) · European Journal of Endocrinology · doi:10.1093/ejendo/lvaf139 · Cited by 3 · see citing works
Takenouchi, H., Anno, T., Iwamoto, H., Takahashi, K., Iwamoto, Y., Horiya, M., Kimura, Y., Kawasaki, F., Kaku, K., Tomoda, K., et al. (2022) · Internal Medicine · doi:10.2169/internalmedicine.8665-21 · Cited by 3 · see citing works
“Since it takes longer to diagnose Cushing’s disease than adrenal Cushing’s syndrome, we should pay closer attention to signs and symptoms of pituitary Cushing’s syndrome overlapping with common diseases (21).”
BackgroundBlasco, L. G., Corrales, P. J. P., Hanzu, F. A., Martínez, A. F., Lesmes, I. B., & Escalada, J. (2023) · Endocrinología Diabetes y Nutrición · doi:10.1016/j.endinu.2023.01.005 · Cited by 3 · see citing works
Self-citationPituitary apoplexy in cushing’s disease: a single center study and systematic literature review
Ragate, D. C., Memon, S. S., Sarathi, V., Lila, A. R., Channaiah, C. Y., Patil, V. A., Karlekar, M. P., Barnabas, R., Thakkar, H. U., Shah, N. S., et al. (2024) · Pituitary · doi:10.1007/s11102-024-01411-1 · Cited by 3 · see citing works
“A delay in diagnosis of CD (mean 38 months) due to its rarity and overlap of its presentation with metabolic syndrome have been reported in a meta-analysis of Cushing’s syndrome [50].”
Higher risk and earlier onset glaucoma in Cushing's syndrome
Sharon, Y., Shochat, T., Rudman, Y., Kushnir, S., Zahavi, A., Shimon, I., Fleseriu, M., & Akirov, A. (2024) · Acta Ophthalmologica · doi:10.1111/aos.16787 · Cited by 3 · see citing works
“This observation, coupled with the well-documented diagnostic delay of CS (Rubinstein et al., 2020), suggests that the hypercortisolism before the formal diagnosis of CS did put them at a heightened risk of developing glaucoma at a younger age.”
Systematic approach to the diagnosis and management of endocrine hypertension
Stowasser, M., Jansen, P. M., & Wolley, M. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-96120-2.00009-1 · Cited by 4 · see citing works
Hamidi, O., St-Jean, M., Lacroix, A., & Bancos, I. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag095 · Cited by 5 · see citing works
Ectopic ACTH Syndrome: Possibilities of Modern Diagnostics
Grineva, E. N., Tsoy, U. A., & Рыжкова, Д. В. (2024) · Annals of the Russian academy of medical sciences · doi:10.15690/vramn12677 · Cited by 2 · see citing works
Bryk, A. H., Minasyan, M., Hubalewska–Dydejczyk, A., & Gilis‐Januszewska, A. (2024) · Endocrine Connections · doi:10.1530/ec-23-0557 · Cited by 3 · see citing works
“Since the time to CS diagnosis is delayed (34), we categorized VTE which occurred prior to the initiation of endocrinological work-up as VTE during active hypercortisolemia.”
BackgroundChanging face of Cushing’s disease over three decades in pituitary center
Muradov, I., Şahin, S., Uysal, S., Sulu, C., Gunebakan, P., Tunc, A., Kocaman, B. B., Soltanova, L., Gazioğlu, N., Tanriover, N., et al. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02702-5 · Cited by 2 · see citing works
Clinical management of ectopic Cushing Syndrome in neuroendocrine neoplasms: a national survey
Laffi, A., Prinzi, A., di Dato, C., Feola, T., Medici, M., Colao, A., Faggiano, A., & Lania, A. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1690837 · Cited by 2 · see citing works
Twist of endocrine scenario: Approach of ectopic Cushing syndrome (review)
Morar, A., Ghemigian, A. M., Ţupea, C., Petrova, E. N., Popescu, M. R., Carşote, M., Dumitru, N., & Valea, A. (2020) · Romanian Journal of Medical Practice · doi:10.37897/rjmp.2020.4.7 · Cited by 2 · see citing works
Blasco, L. G., Corrales, P. J. P., Hanzu, F. A., Martínez, A. F., Lesmes, I. B., & Martín, J. E. S. (2023) · Endocrinología Diabetes y Nutrición (English ed ) · doi:10.1016/j.endien.2023.04.004 · Cited by 2 · see citing works
Self-citationAbordagem geral das características da Síndrome de Cushing
Weksler, F. L., Weksler, G. L., Portela, M. V. M., Nobre, C. F. A., & de Siqueira, E. C. (2023) · Revista Eletrônica Acervo Saúde · doi:10.25248/reas.e12852.2023 · Cited by 2 · see citing works
Balderrama-Soto, A., Rivera-Hernández, A. D. J., Reza-Albarrán, A. A., la Vega, A. N.-D., Vergara-López, A., Monteros-Sánchez, A. L. E. D. L., Navas-Minero, C. E., Abreu-Rosario, C., Cuevas-Ramos, D., Espinosa-Cárdenas, E., et al. (2023) · Revista Mexicana de Endocrinología Metabolismo y Nutrición · doi:10.24875/rme.m23000025 · Cited by 2 · see citing works
Sawamura, T., Kometani, M., Karashima, S., & Yoneda, T. (2024) · BMJ Case Reports · doi:10.1136/bcr-2024-259687 · Cited by 2 · see citing works
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“Even though rapid treatment induction is of utmost priority in CS, time to diagnosis is often signi fi cantly delayed [6 – 8].”
BackgroundPredictors of cancer in patients with endogenous Cushing’s syndrome
Rudman, Y., Drozdinsky, G., Masri‐Iraqi, H., Shochat, T., Kushnir, S., Shimon, I., Fleseriu, M., & Akirov, A. (2025) · Endocrine Related Cancer · doi:10.1530/erc-25-0059 · Cited by 2 · see citing works
Salvio, G., Ciarloni, A., Aboud, N., Ambo, N., Bordoni, M., Lucchetti, B., Martino, M., Perrone, M., Gasparroni, M., Balercia, G., et al. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf681 · Cited by 2 · see citing works
Metformin: the white knight fighting corticosteroid side-effects
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Self-citationEncuesta sobre la docencia pregrado de Endocrinología y Nutrición en España-2021
Pinés-Corrales, P. J., Hanzu, F. A., Fernández, R. C., Martínez, A. F., Pérez, C. T., Escalada, J., & Lesmes, I. B. (2022) · Endocrinología Diabetes y Nutrición · doi:10.1016/j.endinu.2022.05.005 · Cited by 2 · see citing works
Self-citationACTH-dependent Cushing's syndrome
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Abreu-Lomba, A., Rojas, W., Perlaza, F. G., Tovar, H., Tovar, A. P., Syro, L. V., Gutiérrez-Restrepo, J., Román-Gonzaléz, A., Melo, L. J. R., & Rodríguez, N. G. (2023) · Revista Colombiana de Endocrinología Diabetes & Metabolismo · doi:10.53853/encr.10.3.823 · Cited by 2 · see citing works
“[25] Rubinstein G, Osswald A, Hoster E, Losa M, Elenkova A, Zacharieva S, et al.”
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A Corticotropin-Secreting Adenoma in the Setting of von Hippel-Lindau Disease
Chen, X., Zhou, Y., Lü, L., Feng, M., Wang, L., & Tong, A. (2025) · JCEM Case Reports · doi:10.1210/jcemcr/luaf055 · Cited by 1 · see citing works
“Diagnosis of Cushing disease is frequently delayed for several years, partly due to insufficient awareness of the insidious and progressive nature of the disease, as well as the complexity involved in testing [19, 20].”
Szklarz, M., Gontarz-Nowak, K., Górny, J. M., & Matuszewski, W. (2025) · SN Comprehensive Clinical Medicine · doi:10.1007/s42399-025-01994-1 · Cited by 1 · see citing works
“In the past, SCLCs accounted for the vast majority of cases [8].”
- 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
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