USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer.

The contribution of deubiquitylating enzymes (DUBs) to β-Catenin stabilization in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, and by using an unbiassed screen, we discovered that the DUB USP10 stabilizes β-Catenin specifically in APC-truncated CRC in vitro and in vivo. Mechanistic studies, including in vitro binding together with computational modelling, revealed that USP10 binding to β-Catenin is mediated via the unstructured N-terminus of USP10 and is outcompeted by intact APC, favouring β-catenin degradation.

[Adrenal tumors: current standards in clinical management].

Adrenal tumors are among the most common tumors in humans. They are most frequently discovered incidentally during abdominal imaging for other reasons or due to clinical symptoms (e.g.

Prognostic role of quantitative [18F]FDG PET/CT parameters in adrenocortical carcinoma.

Purpose: We aimed to evaluate the prognostic potential of baseline [F]FDG PET/CT for overall survival (OS) in patients with adrenocortical carcinoma (ACC).

Methods: We performed a retrospective analysis of 67 treatment-naïve ACC patients with available [F]FDG PET/CT at time of initial diagnosis. Pretherapeutic PETs of primary tumors were manually segmented and quantitative parameters (maximum/mean/peak standardized uptake value (SUV), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG, defined as TV*SUV) were derived.

Exploring Theranostic Avenues in Adrenocortical Carcinoma Using Chemokine Receptor and Prostate-Specific Membrane Antigen-Directed PET/CT.

We report on an adrenocortical carcinoma (ACC) patient, which has exhausted previous treatment options and was scheduled for prostate-specific membrane antigen (PSMA)- and C-X-C motif chemokine receptor 4 (CXCR4)-targeted PET/CT. We identified PSMA-avid pulmonary metastases exhibiting modest radiotracer accumulation, while chemokine receptor PET/CT provided intense uptake. This dual-tracer molecular imaging approach revealed that chemokine receptor PET appears to be more suitable in patients with advanced ACC, indicating that CXCR4-directed radioligand therapy may be considered in such patients suffering from end-stage disease.

Early Detection of Recurrence and Progress Using Serum Steroid Profiling by LC-MS/MS in Patients with Adrenocortical Carcinoma.

Serum liquid chromatography-tandem mass spectrometry (LC-MS/MS) steroid profiling is used for the diagnosis of adrenocortical carcinoma (ACC). Guidelines recommend endocrine work-up in addition to radiological imaging for follow-up in ACC, but data on this topic are scarce. Patients were included in this retrospective study if pre-therapeutic hormone values, regular tumour evaluation by imaging, steroid measurements by LC-MS/MS, and details on therapies were available.

Current Evidence on Local Therapies in Advanced Adrenocortical Carcinoma.

International guidelines emphasise the role of local therapies (LT) for the treatment of advanced adrenocortical carcinoma (ACC). However, large studies are lacking in this field. Therefore, we performed a review of the literature to synthesise current evidence and develop clinical guidance.

CXCR4-directed PET/CT with [ Ga]Ga-pentixafor in solid tumors-a comprehensive analysis of imaging findings and comparison with histopathology.

Background: C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in various solid cancers and can be targeted by CXCR4-directed molecular imaging. We aimed to characterize the in-vivo CXCR4 expression in patients affected with solid tumors, along with a comparison to ex-vivo findings.

Methods: A total 142 patients with 23 different histologically proven solid tumors were imaged with CXCR4-directed PET/CT using [ Ga]Ga-pentixafor (total number of scans, 152).

High Filamin a Expression in Adrenocortical Carcinomas Is Associated with a Favourable Tumour Behaviour: A European Multicentric Study.

The insulin-like growth factor 2 (IGF2) promotes cell growth by overactivating the IGF system in an autocrine loop in adrenocortical carcinomas (ACCs). The cytoskeleton protein filamin A (FLNA) acts as a repressor of IGF2 mitogenic signalling in ACC cells. The aims of this study were to test FLNA expression by immunohistochemistry in 119 ACCs and 26 adrenocortical adenomas (ACAs) and to evaluate its relationship with clinicopathological features and outcome in ACCs.

Renal complications in chronic hypoparathyroidism - a systematic cross-sectional assessment.

Context: Although renal long-term complications are acknowledged in chronic hypoparathyroidism (HPT), standardized investigations are scarce.

Objective: To systematically investigate renal complications and their predictors in hypoparathyroid patients compared to matched individuals.

Design: Prospective observational study in 161 patients with chronic HPT.

Hypoparathyroidism - management, information needs, and impact on daily living from the patients' perspective: results from a population-based survey.

Purpose: Hypoparathyriodism (hypoPT) is a rare endocrine disorder. It is not known how hypoPT is managed in Germany or whether patients have unmet information needs or impairments in their daily living.

Methods: HypoPT patients at a minimum of 6 months' post-diagnosis were invited to participate in an online survey through their treating physician or through patient organizations.

Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling.

Parathyroid carcinoma (PC) is an ultra-rare malignancy with a high risk of recurrence after surgery. Tumour-directed systemic treatments for PC are not established. We used whole-genome and RNA sequencing in four patients with advanced PC to identify molecular alterations that could guide clinical management.

The metabolic phenotype of patients with primary aldosteronism: impact of subtype and sex - a multicenter-study of 3566 Caucasian and Asian subjects.

Background: Accumulating evidence suggests that primary aldosteronism (PA) is associated with several features of the metabolic syndrome, in particular with obesity, type 2 diabetes mellitus, and dyslipidemia. Whether these manifestations are primarily linked to aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA) remains unclear. The aim of the present study was to investigate differences in metabolic parameters between APA and IHA patients and to assess the impact of treatment on these clinical characteristics.

Treatment of RET-Positive Advanced Medullary Thyroid Cancer with Multi-Tyrosine Kinase Inhibitors-A Retrospective Multi-Center Registry Analysis.

Background: (rearranged during transfection) variants are the most prevalent oncogenic events in medullary thyroid cancer (MTC). In advanced disease, multi-tyrosine kinase inhibitors (MKIs) cabozantinib and vandetanib are the approved standard treatment irrespective of status. The actual outcome of patients with -positive MTC treated with MKIs is ill described.

Improved Diagnostic Accuracy of Clonidine Suppression Testing Using an Age-Related Cutoff for Plasma Normetanephrine.

Background: Moderately elevated plasma normetanephrine (NMN) levels are frequent among patients with suspected pheochromocytoma and paraganglioma (PPGL). Clonidine suppression testing (CST) is recommended to distinguish patients with from those without PPGL. We aimed at evaluating the diagnostic outcome of CST in patients with moderate NMN elevations.

The Saline Infusion Test for Primary Aldosteronism: Implications of Immunoassay Inaccuracy.

Context: Diagnosis of primary aldosteronism (PA) for many patients depends on positive results for the saline infusion test (SIT). Plasma aldosterone is often measured by immunoassays, which can return inaccurate results.

Objective: This study aimed to establish whether differences in aldosterone measurements by immunoassay versus mass spectrometry (MS) might impact confirmatory testing for PA.

[Conn's syndrome-Frequent and still too rarely diagnosed to underdiagnosed].

Conn's syndrome represents the most common cause of endocrine hypertension and is associated with an increased cardiovascular risk, a series of comorbidities (including type 2 diabetes mellitus) and with their frequent occurrence. Therefore, a correct and rapid diagnosis is of essential importance. Measurement of the aldosterone-renin ratio is used as a first screening test for primary aldosteronism.

Expression of the Chemokine Receptor CCR7 in the Normal Adrenal Gland and Adrenal Tumors and Its Correlation with Clinical Outcome in Adrenocortical Carcinoma.

Background: The chemokine receptor CCR7 is crucial for an intact immune function, but its expression is also associated with clinical outcome in several malignancies. No data exist on the expression of CCR7 in adrenocortical tumors.

Methods: CCR7 expression was investigated by qRT-PCR and immunohistochemistry in 4 normal adrenal glands, 59 adrenocortical adenomas, and 181 adrenocortical carcinoma (ACC) samples.

Medullary thyroid cancer with ectopic Cushing's syndrome: A multicentre case series.

Objective: Ectopic Cushing's syndrome (ECS) induced by medullary thyroid cancer (MTC) is rare, and data on clinical characteristics, treatment and outcome are limited.

Design: Retrospective cohort study in three German and one Swiss referral centres.

Patients: Eleven patients with MTC and occurrence of ECS and 22 matched MTC patients without ECS were included.

Real-World Efficacy and Safety of Multi-Tyrosine Kinase Inhibitors in Radioiodine Refractory Thyroid Cancer.

The management of patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that is refractory to radioiodine (RAI) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers.

Reduction of Radiation Exposure in Adrenal Vein Sampling: Impact of the Rapid Cortisol Assay.

Purpose:  To determine radiation exposure associated with adrenal vein sampling and its reduction by implementing the rapid cortisol assay and modification of the sampling protocol.

Materials And Methods:  A single-center retrospective study of adrenal vein sampling performed between August 2009 and March 2020 revealed data from 151 procedures. Three subgroups were determined.

Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management.

Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC.

[Hormones and The Heart - Clinical Cases].

The heart is closely connected with the endocrine system. On the one hand, the heart is an endocrine organ itself and produces several hormones like atrial and brain natriuretic peptides. On the other hand, cardiac structures are targets of many hormones like catecholamines, thyroid hormones, and corticosteroids.