Publications by authors named "Felix Beuschlein"

Context: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection.

Objective: To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection.

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Peripheral neuropathy (PN), the most common complication of diabetes, leads to sensory loss and associated health issues as pain and increased fall risk. However, present treatments do not counteract sensory loss, but only partially manage its consequences. Electrical neural stimulation holds promise to restore sensations, but its efficacy and benefits in PN damaged nerves are yet unknown.

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Introduction: Patients with Cushing's syndrome (CS) suffer from metabolic and cardio-vascular comorbidities caused by hypercortisolism. The human gut microbiome responds to different pathological conditions. Aim of our study was to analyze the impact of chronic endogenous cortisol excess on the gut microbiome.

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Context: Primary aldosteronism (PA) is the most common form of endocrine hypertension. According to the Endocrine Society Practice Guidelines, the diagnosis of PA requires a pathological screening test result and non-suppressible aldosterone levels during confirmatory testing. Sequential testing with more than one confirmatory test may result in discordant test results.

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While immune checkpoint inhibitors (ICIs) have revolutionized modern oncology, they are also associated with immune-related adverse events (irAEs). Previous histopathological descriptions of organ-related inflammatory changes do not consider systemic effects of ICIs, because of an absence of comprehensive autopsy studies. We performed a retrospective study on 42 whole-body autopsies of patients treated with ICIs from January 2011 to March 2024 to determine frequency, organ distribution and morphology of ICIs-associated inflammatory changes as well as their clinical relevance.

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Objective: To study pregnancy outcomes and complications in women with congenital adrenal hyperplasia (CAH).

Methods: A retrospective multicenter study was conducted at tertiary reference centers in 5 countries (Austria, Germany, Italy, Sweden, USA), including 72 adult women with CAH (nonclassic [NC] n = 34, simple virilizing [SV] n = 21, salt wasting [SW] n = 17).

Results: A total of 133 pregnancies, 112 live births, and 25 abortions were documented.

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Article Synopsis
  • - Adrenocortical insufficiency is a serious condition caused by a lack of glucocorticoids and/or mineralocorticoids from the adrenal cortex, leading to life-threatening adrenal crises, requiring immediate hydrocortisone treatment.
  • - Symptoms like low blood pressure, weight loss, and fatigue are often vague, causing delays in diagnosis; the case study involves a 43-year-old woman who experienced adrenal insufficiency due to bleeding in her adrenal glands while also having immune thrombocytopenia (ITP).
  • - Proper diagnosis is crucial, especially in patients with bleeding risk factors, and treatment typically starts with high doses of hydrocortisone and possibly fludrocortisone, which can later be adjusted as
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Background: Distinguishing between unilateral and bilateral primary aldosteronism, a major cause of secondary hypertension, is crucial due to different treatment approaches. While adrenal venous sampling is the gold standard, its invasiveness, limited availability, and often difficult interpretation pose challenges. This study explores the utility of circulating microRNAs (miRNAs) and machine learning in distinguishing between unilateral and bilateral forms of primary aldosteronism.

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  • Somatostatin receptor type 2 (SSTR2) is commonly found on certain tumors, including gastro-entero-pancreatic neuroendocrine tumors and breast cancer, making it a target for therapy.
  • Researchers developed a novel fluorescent-peptide antagonist, Octo-Fluo, that works with genetically engineered CAR T-cells to selectively trigger cell death in SSTR2-expressing cancer cells.
  • In laboratory and animal studies, Octo-Fluo enhanced the effectiveness of AdFITC(E2)-CAR T-cells against tumors, but high concentrations of Octo-Fluo could reduce its effectiveness by saturating both the CAR and SSTR2, highlighting the importance of dosage for treatment success.
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  • Cushing's syndrome (CS) can be tricky to diagnose early, especially in patients with mild symptoms or mild autonomous cortisol secretion (MACS), making a timely diagnosis crucial for effective treatment and better outcomes.
  • In a study involving the German Cushing's registry, researchers analyzed 129 patients with CS and 48 with MACS to assess their clinical signs and comorbidities, finding that both groups had a significant number of health issues, mainly hypertension.
  • The study revealed that many patients with overt CS had only a few clinical signs at diagnosis, highlighting the variability in the symptoms and comorbidities among both CS and MACS patients.
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  • Patients with primary aldosteronism (PA) accompanied by autonomous cortisol co-secretion (ACS) show worse cardiac outcomes and left ventricular hypertrophy compared to those without ACS.
  • A study of 367 PA patients indicated that those with ACS had higher NTpro-BNP levels, which correlate with cortisol levels, signifying more cardiac stress initially and less recovery post-treatment.
  • Over time, only patients without ACS showed significant improvements in heart dimensions and mass, emphasizing the long-term impact of ASC on cardiac health in PA patients.
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  • Hypophysitis, a condition affecting the pituitary gland, occurs in up to 10% of patients receiving immune-checkpoint inhibitors (ICIs) for melanoma, with one-third showing no MRI abnormalities, leading to potentially dangerous delays in diagnosis.
  • This study assessed the effectiveness of FDG PET/CT scans in detecting ICI-induced hypophysitis by comparing patients with the condition to an age- and sex-matched control group, utilizing the target-to-background ratio (TBR) of the pituitary gland.
  • Results indicated that a TBR of around 2.4 can predict impending hypophysitis in melanoma patients on ICI treatment, with a demonstrated sensitivity of 72.7% and specificity of
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  • Endogenous hypercortisolism shows different symptoms, and researchers are seeking to understand what factors influence its severity, especially focusing on the ABCB1 gene's role in glucocorticoid secretion.
  • The study examined 137 patients from the German Cushing's registry to see how the ABCB1 polymorphism rs2032582 affects steroid levels and clinical characteristics.
  • Results showed that patients with cortisol-producing adrenal adenomas who had the major allele GG of the ABCB1 polymorphism had higher cortisol levels and blood pressure compared to those with other genotype variations, suggesting the gene may influence disease severity.
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  • Endothelial dysfunction (ED) is linked to higher cardiovascular disease rates in primary aldosteronism (PA), and the role of the epoxyeicosatrienoic acid (EET) pathway in this context is not well-understood.
  • The study analyzed how aldosterone impacts EET production and endothelial function by using various methods, including qPCR, calcium imaging, and mass spectrometry on both human cells and patient plasma.
  • Findings suggest that while aldosterone alters inflammation and calcium responses in endothelial cells, it does not hinder EET release, indicating that targeting epoxide hydrolase might help reverse these endothelial issues and warrants further investigation as a potential treatment.
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Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed.

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Background: Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR).

Methods: This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate).

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  • Secondary hypogonadism (SH) is prevalent in men with Cushing's syndrome (CS) and mild autonomous cortisol secretion (MACS), significantly impacting testosterone levels.
  • In a study involving 30 men with CS and 17 with MACS, most had low testosterone levels, with improvements observed post-surgery.
  • Despite testosterone levels normalizing after treatment, some red blood cell parameters remained low, suggesting the need for further research.
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While the establishment of human phaeochromocytoma and paraganglioma (PPGL) cell lines has proven to be particularly difficult over several decades of research, there are other reliable pre-clinical PPGL models currently available. This review provides a summary of these models, together with our recently established personalised drug screening platform using patient-derived PPGL primary cultures. Such currently available PPGL models include murine and rat PPGL cell lines, of which only one cell line (PC12) is publicly accessible through a cell repository, and PPGL animal models, of which the patient-derived xenograft models are promising but complex to establish.

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  • - Macrophages are vital for maintaining specific functions and balance in the adrenal gland, particularly in regulating aldosterone production through their interactions with blood vessels.
  • - The study reveals that the absence of the molecule VEGF-A in macrophages leads to changes in blood vessel structure, resulting in increased aldosterone secretion and associated health issues like high blood pressure.
  • - Findings suggest that the communication between macrophages and endothelial cells is crucial for adrenal health and could have significant implications for understanding similar processes in other endocrine organs.
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Background: The benefit of Glucagon-like Peptide-1 (GLP-1) receptor agonists (RAs) in weight reduction against potential harms remains unclear. This study aimed at evaluating the benefit-harm balance of initiating GLP-1 RAs versus placebo for weight loss in people living with overweight and obesity but without diabetes.

Methods: We performed benefit-harm balance modelling, which will be updated as new evidence emerges.

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Background: Normalization of hypercortisolism is essential to reduce morbidity and mortality in patients with Cushing's syndrome (CS). The aim of this analysis was to assess biochemical control rates in patients with Cushing's disease (CD), ectopic Cushing's syndrome (ECS) and adrenal Cushing's syndrome (ACS).

Methods: Patients with confirmed CS (n= 296) treated in a single tertiary care center were retrospectively analysed (185 CD, 27 ECS, 84 uni- and bilateral ACS).

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Background: Clinical practice guidelines recommend the Lateralization Index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA). Our goal was to identify the optimal LI cut-offs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure.

Methods: We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1,550 patients with PA who underwent AVS, with and/or without ACTH stimulation.

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Article Synopsis
  • - Glucocorticoids are commonly used medications for inflammation and immune suppression, but over 1% of users may face a risk of adrenal insufficiency based on dosage, duration, and individual factors.
  • - Managing adrenal insufficiency can be complex, especially when trying to taper off glucocorticoids, as withdrawal symptoms can mimic those of adrenal insufficiency.
  • - A new joint guideline from the European Society of Endocrinology and Endocrine Society offers important recommendations for healthcare providers to effectively care for patients undergoing long-term glucocorticoid therapy.
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