Incidence of Cushing’s syndrome in patients with significant hypercortisoluria

Hirsch, Dania; Tsvetov, Gloria; Manisterski, Yossi; Aviran-Barak, Nirit; Nadler, Varda; Alboim, Sandra; Kopel, Vered

doi:10.1530/eje-16-0631

Cited by 12 publications

(6 citation statements)

References 33 publications

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“…The study was based on data on patients younger than 65 years of age from a large insurance database where the diagnosis was based on diagnostic codes for CS, and the medical records were not reviewed for validation of the diagnosis. In another recently published study from Israel by Hirsch et al, based on data from a large health care database, the mean annual incidence of CS between 2005 and 2014 was 4.5 cases per million, also higher than previously reported. Of note is that in both the study by Broder and Hirsch, patients in the databases without CS were used as the denominator for calculation of incidence.…”

Section: Discussioncontrasting

confidence: 78%

“…8,9 In highly cited review articles on endogenous CS, 1,12 the proportion of patients with ectopic CS is typically considered to be 10%. Also, in one of the largest study on ectopic CS published today, 13 Hirsch et al, 16 based on data from a large health care database, the mean annual incidence of CS between 2005 and 2014 was 4.5 cases per million, also higher than previously reported. Of note is that in both the study by Broder and Hirsch, patients in the databases without CS were used as the denominator for calculation of incidence.…”

Section: Discussionmentioning

confidence: 75%

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The incidence of endogenous Cushing's syndrome in the modern era

Wengander

Trimpou

Papakokkinou

et al. 2019

Clinical Endocrinology

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Introduction Epidemiological studies on the incidence of Cushing's syndrome (CS) are few and most often includes only patients with the most common form, that is Cushing's disease (CD). Objective To analyse the incidence of endogenous CS in an unselected cohort of patients from western Sweden between 2002 and 2017. Methods Medical records from patients who had received a diagnostic code for CS and adrenocortical carcinoma in the Västra Götaland County between 2002 and 2017 were reviewed. Eighty‐two patients had been diagnosed with endogenous CS in the region during the study period and were included in this analysis. Results Thirty‐nine patients (48%) had CD, 21 (26%) had ectopic ACTH‐producing tumour, 17 (21%) had a benign adrenal CS, and 5 (6%) had cortisol‐producing adrenocortical carcinoma. Nine of 21 (43%) patients with ectopic CS had an ACTH‐producing lung tumour, 4 had a neuroendocrine pancreas tumour, and 5 had an occult tumour. The annual incidence of endogenous CS was 3.2 cases per million/y; 1.5 for CD, 0.8 for ectopic CS, 0.7 for benign adrenal CS and 0.2 for adrenocortical carcinoma. Conclusions Approximately three new cases of endogenous CS, per one million inhabitants, were diagnosed annually between 2002 and 2017. Compared with previous reports, proportionally more patients had ectopic CS. The reason for this is unclear although increased awareness of hypercortisolism in patients with malignant tumours in the modern era is a possible explanation.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 75%

The incidence of endogenous Cushing's syndrome in the modern era

Wengander

Trimpou

Papakokkinou

et al. 2019

Clinical Endocrinology

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“…Sustained clinical evidence supports the association of neutrophilia with morbid obesity and metabolic syndrome, as well as an increased morning cortisol in obese subjects [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface Markers

Aranda

Lopez

Fernández-Ruiz

et al. 2017

International Journal of Endocrinology

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Glucocorticoids (GC) induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH) has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC). Aim. To investigate adhesion and activation surface cell markers (CDs) of peripheral IMNC in endogenous Cushing syndrome (CS) and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D), 10 ACTH-independent (ACTH-ID) CS, and 16 healthy controls (C) were included. Leukocytes (Leuc), monocytes (MN), lymphocytes (Lym), and neutrophils (N) were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p < 0.05), WC (p < 0.001), WHR (p = 0.003), BMI (p < 0.001), and hs-CRP (p < 0.001). CD14++CD16+ (p = 0.047); CD14+CD16++ (p = 0.053) MN; CD15+ (p = 0.027); CD15+CD16+ (p = 0.008) N; and NK-Lym (p = 0.019) were higher in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 ± 3.5%) versus ACTH-D CS (4.2 ± 1.9%) versus C (4.9 ± 2.3%). NK-Lym correlated with c-LDL (r = 0.433, p = 0.039) and CD15+ N with hs-CRP (r = 0.446, p = 0.037). In multivariate analysis, Leuc, N, and MN depended on BMI (p = 0.021), WC (p = 0.002), and WHR (p = 0.014), while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p = 0.035). Conclusion. In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH.

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“…All patients referred to the Endocrine Institute of Rabin Medical Center and diagnosed with CD between 2000 and 2020 were included. The recruitment of the patients treated for CD at Maccabi Healthcare Services has been previously described [ 10 ]. The computerized database of the HMO was screened for all individuals who fulfilled the following criteria: The recorded biochemical data were compatible with a CD diagnosis as stipulated in the Endocrine Society Clinical Guidelines [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?

Akirov

Shimon

Fleseriu

et al. 2022

JCM

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Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing’s disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to November 31, 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2×ULN vs. 1.3 ± 0.8 × ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study.

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Incidence of Cushing’s syndrome in patients with significant hypercortisoluria

Abstract: The incidence of CS is higher than previously suggested. The consistently increasing number of UFC tests being performed has not been accompanied by a similar increase in CS detection rate. The expected yield of routine UFC testing before bariatric surgery is low.

Cited by 12 publications

References 33 publications

The incidence of endogenous Cushing's syndrome in the modern era

The incidence of endogenous Cushing's syndrome in the modern era

Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface Markers

Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?

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