Refine
Has Fulltext
- yes (65)
Is part of the Bibliography
- yes (65)
Year of publication
Document Type
- Journal article (64)
- Conference Proceeding (1)
Language
- English (65)
Keywords
- adrenocortical carcinoma (9)
- obesity (5)
- metabolomics (4)
- 18F-FDG (3)
- CXCR4 (3)
- Cushing’s syndrome (3)
- FGFR (3)
- PET (3)
- adrenocortical cancer (3)
- biomarker (3)
- hypercortisolism (3)
- liraglutide (3)
- paraganglioma (3)
- pheochromocytoma (3)
- positron emission tomography (3)
- therapy (3)
- vandetanib (3)
- ACTH (2)
- C-X-C motif chemokine receptor 4 (2)
- CYP2W1 (2)
- Cushing’s disease (2)
- FGF-pathway (2)
- PPGL (2)
- Positronen-Emissions-Tomografie (2)
- TKI (2)
- [68Ga]PentixaFor (2)
- adenomas (2)
- adrenal cancer (2)
- adrenal tumours (2)
- adrenocortical tumors (2)
- cancer (2)
- carcinomas (2)
- cardiovascular events (2)
- chemokine receptor (2)
- cortisol (2)
- endoradiotherapy (2)
- gastric bypass (2)
- immune response (2)
- immunohistochemistry (2)
- immunotherapy (2)
- machine learning (2)
- medullary thyroid carcinoma (2)
- mitotane (2)
- mortality (2)
- pediatric adrenocortical cancer (2)
- pediatric adrenocortical tumor (2)
- peptide tyrosine tyrosine (PYY) (2)
- prognosis (2)
- recurrence (2)
- theranostics (2)
- treatment (2)
- tyrosine kinase inhibitor (2)
- 2- deoxy-2-(18F)fluoro-D-glucose (1)
- 2-deoxy-2-(18F)fluoro-D-glucose (1)
- ALT (1)
- ATRX (1)
- Adrenocortial carcinomas (1)
- Antigen 4 (1)
- Autoimmune-Diseases (1)
- BIRC7 (1)
- BRAF(V600E) mutation (1)
- Biochemical-Diagnosis (1)
- CCR7 (1)
- CRH stimulation test (1)
- CTNNB1 (1)
- CXCR7 (1)
- CYP2B6 (1)
- Cell lung canger (1)
- Contrast-enhanced CT (1)
- Copeptin (1)
- Cushing (1)
- Cushing's disease (1)
- Cushings syndrome (1)
- Dendritic Cells (1)
- Diagnosis (1)
- Disease prevalence (1)
- EMT (1)
- F-18-FDG PET/CT (1)
- FGF21 (1)
- FGFR-inhibitors (1)
- Fibroblast Growth Factor-21 (1)
- FoxP3 Expression (1)
- GLP-1 (1)
- Immune-System (1)
- Immunological Self-Tolerance (1)
- Klotho-related molecules (1)
- LND (1)
- LNE (1)
- MASS (1)
- MR (1)
- MTL30 (1)
- Medicine (1)
- Medizin (1)
- Medullärer Schilddrüsenkrebs (1)
- Men (1)
- Metanephrine (1)
- Methodological quality (1)
- Multiple-Sclerosis (1)
- NAFLD (1)
- NASH (1)
- NMR (1)
- NOP10 (1)
- NR3C1 (1)
- Normetanephrine (1)
- PD-L1 (1)
- PF-05231023 (1)
- PYY3-36 (1)
- Paraganglioma (1)
- Plasma (1)
- Positron-emission-tomography (1)
- RNA Expression (1)
- RNAScope (1)
- RYGB (1)
- Resistance (1)
- Roux-en-Y Gastric Bypass (1)
- Roux-en-Y gastric bypass (1)
- Roux-en-Y gastric bypass surgery (1)
- SNP (1)
- SOAT1 (1)
- Sex-Hormones (1)
- Society (1)
- Spin echo (1)
- Suppressive Function (1)
- Systemic-Lupus-Erythematosus (1)
- TERT (1)
- Test accuracy (1)
- USP8 (1)
- Utility (1)
- [11C]-Choline PET/CT (1)
- [11C]-Methionine (1)
- [177Lu]/[90Y]PentixaTher (1)
- [177Lu]PentixaTher (1)
- [18F]FDG-PET-CT (1)
- [90Y]PentixaTher (1)
- [99mTc]-Sestamibi scan (1)
- abdominal lymph node metastases (1)
- adjuvant platinum-based chemotherapy (1)
- adjuvant treatment (1)
- adrenal (1)
- adrenal cortex hormones (1)
- adrenal cortex neoplasms (1)
- adrenal glands (1)
- adrenal imaging (1)
- adrenal surgery (1)
- adrenal tumor (1)
- adrenal tumors (1)
- adrenalectomia (1)
- adrenocortical (1)
- adrenocortical adenocarcinoma (1)
- adrenocortical carcinoma (ACC) (1)
- adrenocortical development (1)
- adrenocortical tissues (1)
- aldosterone (1)
- association (1)
- autoantibodies (1)
- autonomous cortisol secretion (1)
- balance (1)
- bioinformatic clustering (1)
- biomarker prediction (1)
- biomarkers (1)
- blood pressure (1)
- branched-chain amino acids (1)
- cancer detection (1)
- cancer diagnosis (1)
- cancer treatment (1)
- cancer-testis antigens (1)
- carcinogenesis (1)
- carcinoma (1)
- carcinoma metastases to pancreas (1)
- cardiovascular risk factors (1)
- caspase-3 (1)
- catecholamines (1)
- catenin (1)
- cells (1)
- cholesterol metabolism (1)
- chromosomes (1)
- circulating microRNA (1)
- combination (1)
- comparability (1)
- comparative genomic hybridization (1)
- complication (1)
- confounders (1)
- copeptin (1)
- cortisol-producing adenoma (1)
- cytoplasmic staining (1)
- deubiquitinases (1)
- dexamethasone suppression test (1)
- diabetes insipidus (1)
- diagnosis (1)
- disease score (1)
- disease severity (1)
- dissection (1)
- distant metastases (1)
- dogs (1)
- drug therapy (1)
- early prognosis (1)
- ectopic (1)
- efficacy (1)
- endogenous hypercortisolism (1)
- epithelial markers (1)
- expression (1)
- feature selection (1)
- focused surgical approach (1)
- follow-up (1)
- genetic loci (1)
- glucocorticoid excess (1)
- guidelines (1)
- high dose dexamethasone suppression test (1)
- high-resolution analysis (1)
- hormones (1)
- hypothalamic gene expression (1)
- imaging (1)
- immune check inhibitor (1)
- immune checkpoint inhibitor (ICI) (1)
- immunity (1)
- immunohistochemistry techniques (1)
- in silico analysis (1)
- insulin resistance (1)
- intragastric balloon (1)
- isturisa (1)
- kidney disease (1)
- kinase (1)
- kinases (1)
- liquid chromatography–tandem mass spectrometry (LC–MS/MS) (1)
- livin (1)
- lymph node dissection (1)
- lymphadenectomy (1)
- lymphocytes (1)
- malignant tumors (1)
- management (1)
- mass spectrometry (1)
- mass spectronomy (1)
- medical therapy (1)
- mesenchymal markers (1)
- meta-analysis (1)
- metyrapone (1)
- miR-182-5p (1)
- miR-183 cluster (1)
- miR-483-5p (1)
- miRNA (1)
- molecular diagnostics (1)
- morbidity (1)
- multicenter (1)
- multiple myeloma (1)
- mutation (1)
- mutation triggers (1)
- neuroblastoma – diagnosis (1)
- neutral loss (1)
- normal adrenal glands (1)
- normal values (1)
- notch signaling (1)
- nuclear staining (1)
- operation (1)
- osilodrostat (1)
- osmotic stimulation (1)
- outcome (1)
- paired (1)
- papillary (1)
- papillary thyroid carcinoma (PTC) (1)
- parathyroid adenoma (1)
- parathyroid carcinoma (1)
- pathogenesis (1)
- patient survival (1)
- pediatric (1)
- pediatric adrenocortical adenoma (1)
- pediatric adrenocortical carcinoma (1)
- pembrolizumab (1)
- peptide tyrosine tyrosine 3-36 (PYY3-36) (1)
- peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) (1)
- personalized medicine (1)
- phosphatidylcholines (1)
- phosphorylation (1)
- pituitary adenomas (1)
- pituitary gland (1)
- plasma (1)
- plasma NMR (1)
- polarization (1)
- preanalytical conditions (1)
- precision medicine (1)
- predictive marker (1)
- primary hyperparathyroidism (1)
- primary polydipsia (1)
- prognostic biomarker (1)
- prognostic factors (1)
- prospective (1)
- prostate cancer (1)
- protein expression (1)
- radical resection (1)
- radioiodine (1)
- radioiodine therapy (1)
- radiotherapy (1)
- radiotherapy (RT) (1)
- recurrence free survival (1)
- recurrence-free survival (1)
- reference data (1)
- repeated surgery (1)
- review (1)
- rodent model (1)
- rygb (1)
- selpercatinib (1)
- serum (1)
- signs and symptoms (1)
- sleeve gastrectomy (1)
- somatic mutations (1)
- sphingolipids (1)
- steroid measurement (1)
- sudden cardiac death (1)
- super-obesity (1)
- surgery (1)
- surgical oncology (1)
- surgical treatment (1)
- t-lymphocytes (1)
- targeted metabolomics (1)
- targeted treatment (1)
- telomeres (1)
- thyroid carcinoma (TC) (1)
- timing (1)
- transgenic rats (1)
- tumor microenvironment (1)
- tumor-infiltrating (1)
- tumors (1)
- tyrosine kinase inhibitor (TKI) (1)
- unsupervised clustering (1)
- urine (1)
- volume (1)
Institute
- Medizinische Klinik und Poliklinik I (65) (remove)
Sonstige beteiligte Institutionen
Objective:
Adrenal masses are incidentally discovered in 5% of CT scans. In 2013/2014, 81 million CT examinations were undertaken in the USA and 5 million in the UK. However, uncertainty remains around the optimal imaging approach for diagnosing malignancy. We aimed to review the evidence on the accuracy of imaging tests for differentiating malignant from benign adrenal masses. Design: A systematic review and meta-analysis was conducted.
Methods:
We searched MEDLINE, EMBASE, Cochrane CENTRAL Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index, and ZETOC (January 1990 to August 2015). We included studies evaluating the accuracy of CT, MRI, or F-18-fluoro-deoxyglucose (FDG)-PET compared with an adequate histological or imaging-based follow-up reference standard.
Results:
We identified 37 studies suitable for inclusion, after screening 5469 references and 525 full-text articles. Studies evaluated the accuracy of CT (n = 16), MRI (n = 15), and FDG-PET (n = 9) and were generally small and at high or unclear risk of bias. Only 19 studies were eligible for meta-analysis. Limited data suggest that CT density >10 HU has high sensitivity for detection of adrenal malignancy in participants with no prior indication for adrenal imaging, that is, masses with <= 10 HU are unlikely to be malignant. All other estimates of test performance are based on too small numbers.
Conclusions:
Despite their widespread use in routine assessment, there is insufficient evidence for the diagnostic value of individual imaging tests in distinguishing benign from malignant adrenal masses. Future research is urgently needed and should include prospective test validation studies for imaging and novel diagnostic approaches alongside detailed health economics analysis.
Objective
To evaluate diagnostic accuracy of the corticotropin-releasing hormone (CRH) stimulation test and the overnight 8 mg dexamethasone suppression test (DST) for the differentiation of Cushing’s disease (CD) and ectopic Cushing’s syndrome (ECS).
Methods
Retrospective study in 6 European centers. Inclusion criteria: patients with a) overt adrenocorticotropin (ACTH)-dependent Cushing’s syndrome at the time of dynamic testing, b) histopathological confirmed tumors and/or c) postoperative biochemical remission and/or adrenal insufficiency. Optimal cut-offs were calculated via receiver operating characteristic (ROC) analysis using CD as reference.
Results
469 patients were analyzed [78% females; median age 43 years (IQR 19)]. CRH test and overnight 8 mg DST were performed in 420 [CD, n=394 (94%); ECS, n=26 (6%)] and 237 patients [228 CD (96%), 9 ECS (4%)]. Both tests were performed in 205 patients (44%). The post-CRH %-increase at 30 minutes of both ACTH (cut-off ≥31%, sensitivity 83%, specificity 85%, AUC 0.81) and cortisol (cut-off ≥12%, sensitivity 82%, specificity 89%, AUC 0.86) discriminated best between CD and ECS. A test duration of >60 minutes did not improve diagnostic performance of the CRH test. The optimal cortisol cut-off for the %-suppression during the 8 mg DST was ≥55% (sensitivity 80%, specificity 78%, AUC 0.75).
Conclusion
The CRH test has equivalent sensitivity but higher specificity than the 8 mg DST and is therefore the test of first choice. The diagnostic outcome of ACTH and cortisol is well comparable, however, sampling beyond 60 minutes post-CRH does not provide diagnostic benefits.
The occurrence of different subtypes of endogenous Cushing’s syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing’s disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the β-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.
Background
Although surgery is considered the first-line treatment for patients with endogenous Cushing’s syndrome (CS), medical therapy is often required to control severe hypercortisolism. Metyrapone and osilodrostat are both steroidogenic inhibitors targeting the 11β-hydroxylase, however, their therapeutic effectiveness has not yet been directly compared. This study aimed to evaluate metyrapone and osilodrostat in the short-term therapy of CS.
Methods
Retrospective analysis of patients with endogenous CS treated with metyrapone or osilodrostat as monotherapy for at least 4 weeks. Main outcome measures were serum cortisol and 24h urinary free cortisol (UFC) at baseline (T0) and after 2 (T1), 4 (T2), and 12 weeks (T3) of therapy.
Results
16 patients with endogenous CS were identified (pituitary n=7, adrenal n=4, ectopic CS n=5). Each 8 patients were treated with metyrapone and osilodrostat. Despite heterogeneity, both groups showed comparable mean UFC levels at T0 (metyrapone: 758 µg/24h vs osilodrostat: 817 µg/24h; p=0.93). From T0 to T1, the decrease of UFC was less pronounced under metyrapone than osilodrostat (-21.3% vs -68.4%; median daily drug dose: 1000 mg vs 4 mg). This tendency persisted at T2 (-37.3% vs -50.1%; median drug dose: 1250 mg vs 6 mg) while at T3 a decrease in UFC from T0 was more pronounced in the metyrapone group (-71.5% vs -51.5%; median dose 1250 mg vs 7 mg). Under osilodrostat, a QTc-interval prolongation was identified at T3 (mean 432 ms vs 455 ms). From T0 to T2, the number of antihypertensive drugs remained comparable under metyrapone and decreased under osilodrostat (n= -0.3 vs n= -1.0).
Conclusion
Although both drugs show comparable therapeutic efficacy, osilodrostat seems to reduce cortisol levels and to control blood pressure faster.
Impact of the Chemokine Receptors CXCR4 and CXCR7 on Clinical Outcome in Adrenocortical Carcinoma
(2020)
Chemokine receptors have a negative impact on tumor progression in several human cancers and have therefore been of interest for molecular imaging and targeted therapy. However, their clinical and prognostic significance in adrenocortical carcinoma (ACC) is unknown. The aim of this study was to evaluate the chemokine receptor profile in ACC and to analyse its association with clinicopathological characteristics and clinical outcome. A chemokine receptor profile was initially evaluated by quantitative PCR in 4 normal adrenals, 18 ACC samples and human ACC cell line NCI-H295. High expression of CXCR4 and CXCR7 in both healthy and malignant adrenal tissue and ACC cells was confirmed. In the next step, we analyzed the expression and cellular localization of CXCR4 and CXCR7 in ACC by immunohistochemistry in 187 and 84 samples, respectively. These results were correlated with clinicopathological parameters and survival outcome. We detected strong membrane expression of CXCR4 and CXCR7 in 50% of ACC samples. Strong cytoplasmic CXCR4 staining was more frequent among samples derived from metastases compared to primaries (p=0.01) and local recurrences (p=0.04). CXCR4 membrane staining positively correlated with proliferation index Ki67 (r=0.17, p=0.028). CXCR7 membrane staining negatively correlated with Ki67 (r=−0.254, p=0.03) but positively with tumor size (r=0.3, p=0.02). No differences in progression-free or overall survival were observed between patients with strong and weak staining intensities for CXCR4 or CXCR7. Taken together, high expression of CXCR4 and CXCR7 in both local tumors and metastases suggests that some ACC patients might benefit from CXCR4/CXCR7-targeted therapy.
A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.
Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing’s syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects and establish unbiased disease biomarkers. Plasma samples were obtained from 13 biobanks across seven countries and analyzed using untargeted NMR metabolomics. We compared unstratified samples of 106 PHT patients to 231 EHT patients, including 104 PA, 94 PPGL and 33 CS patients. Spectra were subjected to a multivariate statistical comparison of PHT to EHT forms and the associated signatures were obtained. Three approaches were applied to investigate and correct confounding effects. Though we found signatures that could separate PHT from EHT forms, there were also key similarities with the signatures of sample center of origin and sample age. The study design restricted the applicability of the corrections employed. With the samples that were available, no biomarkers for PHT vs. EHT could be identified. The complexity of the confounding effects, evidenced by their robustness to correction approaches, highlighted the need for a consensus on how to deal with variabilities probably attributed to preanalytical factors in retrospective, multicenter metabolomics studies.
Purpose
Pheochromocytomas and Paragangliomas (PPGL) result in chronic catecholamine excess and serious health complications. A recent study obtained a metabolic signature in plasma from PPGL patients; however, its targeted nature may have generated an incomplete picture and a broader approach could provide additional insights. We aimed to characterize the plasma metabolome of PPGL patients before and after surgery, using an untargeted approach, and to broaden the scope of the investigated metabolic impact of these tumors.
Design
A cohort of 36 PPGL patients was investigated. Blood plasma samples were collected before and after surgical tumor removal, in association with clinical and tumor characteristics.
Methods
Plasma samples were analyzed using untargeted nuclear magnetic resonance (NMR) spectroscopy metabolomics. The data were evaluated using a combination of uni- and multi-variate statistical methods.
Results
Before surgery, patients with a nonadrenergic tumor could be distinguished from those with an adrenergic tumor based on their metabolic profiles. Tyrosine levels were significantly higher in patients with high compared to those with low BMI. Comparing subgroups of pre-operative samples with their post-operative counterparts, we found a metabolic signature that included ketone bodies, glucose, organic acids, methanol, dimethyl sulfone and amino acids. Three signals with unclear identities were found to be affected.
Conclusions
Our study suggests that the pathways of glucose and ketone body homeostasis are affected in PPGL patients. BMI-related metabolite levels were also found to be altered, potentially linking muscle atrophy to PPGL. At baseline, patient metabolomes could be discriminated based on their catecholamine phenotype.
Background
Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin.
Case presentation
Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred.
Conclusion
Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.
A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence.