European Journal of Endocrinology

#CoMICWednesday #EJECoMICs Ep 54: NEW European Journal of Endocrinology paper: Association of Body Composition with Adrenal Hormones: A Large Cross-Sectional Single-Centre Study https://lnkd.in/etKrvhp8 By Simba Comics led by Mukunth Kowsik European Society of Endocrinology

The effect of first intervention on cardiac parameters in patients with acromegaly: a systematic review Authors Kevin Anthony Huynh, Jin A. , José M. Montero Cabezas, Linda Scheffers, Marco Verstegen, Nienke Biermasz, Eva C. Coopmans EJE Volume 192, Issue 2, February 2025 Open access paper ?? https://lnkd.in/exhjCKeF Abstract Objective Cardiovascular disease in acromegaly patients remains a major cause of morbidity and all-cause mortality. This systematic review investigates the effect of the first growth hormone-lowering intervention on cardiac parameters. Design Systematic review. Methods Studies evaluating cardiac parameters following the first intervention in acromegaly published up to February, 25, 2022 were included in this systematic review. Risk of bias was assessed using a modified Newcastle–Ottawa Scale and Joanna Briggs Institute Critical Appraisal Checklist. Primary treatment modalities included (transsphenoidal) surgery and medical treatment with first-generation somatostatin receptor ligands. Cardiac outcome measures were divided into cardiac structure (left ventricular hypertrophy [LVH], [indexed] left ventricular mass [LVM/LVMi]) and cardiac function (left ventricular ejection fraction [LVEF] and E/A ratio). Results Twenty-six studies (17 cohort studies and 9 case reports) were included out of 2541 potential studies. The risk of bias analysis categorized, 24 studies as low risk and 2 studies as intermediate risk. Disease-associated changes in cardiac structure and function generally improved in most studies following primary treatment. Left ventricular mass/left ventricular mass index significantly decreased in 9/15 studies and the prevalence of LVH in 3/13 studies. Left ventricular ejection fraction significantly increased in 9/14 studies and the E/A ratio in 6/7 studies. Despite the limited number of studies, cardiac structure improved more in patients achieving biochemical remission than in those failing to achieve biochemical remission. Conclusions Acromegaly associated structural and functional myocardial changes improve with both medical and surgical treatment. Normalizing or even reducing growth hormone/insulin-like growth factor 1 levels may be key in the prevention of further progression of cardiac involvement in acromegaly and adverse cardiac outcomes. EJE Volume 192, Issue 2, February 2025 Open access paper ?? https://lnkd.in/exhjCKeF #endocrinology #acromegaly

BRIEF REPORT Real-life Experience on Efficacy and Safety of Setmelanotide Treatment in Prepubertal Children Authors Ahmet Kahveci, Ilknur Kurt, Serap DEMIRCIOGLU Turan, Tulay Guran, Abdullah Bereket, Belma Haliloglu Abstract Monogenic obesity, characterized by severe, early-onset obesity due to single-gene defects, often resists traditional weight management strategies. This report presents real-life experiences on the efficacy and safety of setmelanotide, an MC4R agonist, in 4 prepubertal children (ages 3-9) with LEPR and POMC deficiencies. Findings indicate that setmelanotide is effective at lower doses in our patients with POMC deficiency (0.3-0.5?mg/day) than the patients with LEPR deficiency (2.5?mg/day). Treatment was generally well-tolerated, with injection site reactions and hyperpigmentation as common side effects. As novel findings, gonadotropin-related effects such as hypothalamo-pituitary-gonadal axis activation and testicular descent were observed in 2 patients. Growth deceleration was noted in 2 children, and recovery from central hypothyroidism in 1 patient with POMC deficiency. Overall, setmelanotide appears to be effective and well-tolerated in young children with monogenic obesity. However, further studies are necessary to evaluate the long-term effects of early intervention on growth and pubertal development. EJE Volume 192, Issue 2, February 2025 Full paper ?? https://lnkd.in/eAdTtAc8 ESE Members free access via ?? https://lnkd.in/ep48a8bR #endocrinology #setmelanotide #gonadotropin #hormones

Endocrine dysfunction in long term survivors of pediatric head and neck rhabdomyosarcoma Authors Michèle Morfouace, Reineke Schoot, Marinka Hol, Véronique Minard-Colin, Frederic Kolb, Stephanie Bollé, Matumba T Kayembe, Mark N Gaze, Eric Sandler, Rutger Knops, Johannes H M Merks, Ludwig E Smeele, Daniel J Indelicato, Olga Slater, Hanneke van Santen EJE Volume 192, Issue 1, January 2025 Open access paper ?? https://lnkd.in/eTJJedJg Abstract Objective Survivors of pediatric head and neck rhabdomyosarcoma (HNRMS) are at risk of developing endocrinopathies following local treatment, resulting from radiation damage to the pituitary gland, hypothalamus, or thyroid gland, often at a young age. Our aim was to determine the prevalence of endocrine dysfunction in long-term HNRMS survivors and compare the prevalence of anterior pituitary insufficiency (API) among different local treatment strategies: external beam radiation with photons, external beam radiation with protons, microscopically radical surgery combined with external irradiation, and macroscopic radical surgery combined with brachytherapy. Design and methods Head and neck rhabdomyosarcoma survivors treated between 1993 and 2017, with ≥2 years of follow-up, without recurrent disease or secondary malignancy were eligible for this study. The presence of any endocrine dysfunction was assessed cross-sectionally using Common Terminology Criteria of Adverse Events grading, anthropometrics, and biochemical testing. Retrospective chart review was added to this clinical assessment. Results Ninety-six survivors with long follow-up time (median, 9 years) were included. Any endocrinopathy was present in 35% of survivors, with 88% having pituitary, 6% peripheral (thyroid), and 6% combined insufficiencies. None had gonadal insufficiency. Growth hormone deficiency was diagnosed in 31 (32%) survivors, with additional pituitary insufficiencies in 12 (39%). In 8%, central precocious puberty preceded API. None of the survivors given brachytherapy had API. Conclusions The prevalence of pituitary dysfunction in HNRMS survivors is high, emphasizing the importance of systematic endocrine assessment during follow-up, including pubertal development and growth. Efforts should be made to further reduce extraneous irradiation to endocrine organs to prevent dysfunction later in life. EJE Volume 192, Issue 1, January 2025 Open access paper ?? https://lnkd.in/eTJJedJg #endocrinology #radiotherapy #rhabdomyosarcoma

A new broom sweeps clean: CLDN16 surpasses the BRAF-V600E mutation as an unrivaled biomarker in papillary thyroid cancer Authors Yefeng Cai, Yawen Guo, Wenli Ma, Pu Cheng, Liehao Jiang, Shuyan Shen, Fahuan Song, Lei Zhu, Yiqun Hu, Yao Chen, Yanting Duan, Xiujun Cai, Quan Li, Guowan Zheng, Minghua Ge Abstract Objective This study assessed CLDN16 as a potential replacement or improvement biomarker for papillary thyroid cancer (PTC), addressing the limitations associated with the prevalently used BRAF-V600E mutation. Design Database analyses, tissue validation, RNA sequencing, and functional assays were conducted to evaluate CLDN16 as a PTC biomarker and its clinical application. Methods CLDN16 expression was examined in PTC and normal thyroid/para-tumor tissues and compared across various cancer types. We evaluated diagnostic accuracy, stability in primary and metastatic sites, and associations with aggressive features. Knockdown experiments were performed to investigate the impact on PTC cell behavior. Additionally, we developed a support vector machine model for diagnosing malignant and high-risk PTCs. Results CLDN16 demonstrated high specificity for PTC, with positive detection rates (88.0% in The Cancer Genome Atlas [TCGA] and 88.3% in our center) significantly surpassing BRAF-V600E (47.5% in TCGA and 74.3% in our center). This resulted in superior diagnostic accuracy (ROC-CLDN16 = 0.922 vs ROC-BRAF-V600E = 0.742 in TCGA). CLDN16 exhibited stable expression across primary and metastatic sites and was associated with aggressive features, including extrathyroidal extension and lymph node metastasis. CLDN16 knockdown inhibited migration, invasion, and iodine uptake in PTC cells. Clinically, CLDN16 effectively identified malignancy in BRAF wild patients (94.2%), and combined with BRAF-V600E, achieved 96.9% accuracy. The incorporation of CLDN16 into PTC molecular typing facilitated precise high-risk identification (92.0% accuracy in the training set and 100% in the validation set). Conclusions CLDN16 presents a promising biomarker that could surpass BRAF-V600E, offering effective clinical utility and revolutionizing PTC molecular typing for precise high-risk identification. EJE Volume 192, Issue 2, February 2025 Full paper ?? https://lnkd.in/e4gs7Vcm ESE Members free access via ?? https://lnkd.in/ep48a8bR #endocrinology #CLDN16 #BRAF-V600E #thyroid #papillarythyroidcancer #biomarker

Hormonal regulation of human adipose tissue lipolysis: impact of adipose GIP system in overweight and obesity Authors Sebastian Brachs, Dominik Soll, Finja Beer, nadine huckauf, Anish Konkar, Joachim Spranger, Hartmut Rütten, Knut Mai Abstract Objective Given the promising effects of GLP-1/GIP/glucagon receptor triagonists on weight loss in animals and humans, improved understanding of underlying mechanism is required. We investigated a direct lipolytic effect of a specific GLP-1/GIP/glucagon receptor triagonist on human adipose tissue to disentangle central and peripheral effects as potential drivers of weight loss. Design and methods Isolated primary adipocytes from subcutaneous adipose tissue biopsies of 22 non-diabetic subjects [63.0 (57.0-69.5) years] were incubated with increasing concentrations of isoprenaline, GLP-1, GIP, glucagon, or a GLP-1/GIP/glucagon receptor triagonist. Glycerol concentration was measured following stimulation to assess lipolysis. mRNA expression of adipose tissue receptors was analyzed in parallel. Results Glycerol concentration only increased by isoprenaline, GIP (+13%), and GLP-1/GIP/glucagon receptor triagonist (+28%) but not by GLP-1 or glucagon. This effect was not related to age or body mass index (BMI). Higher adipose tissue GIP receptor mRNA expression was related to elevated glycerol release after GIP and GLP-1/GIP/glucagon receptor triagonist stimulation. Conclusions Direct lipolytic effects of GIP seem to exist in human subcutaneous adipose tissue. This might be targetable by multiple receptor agonists, especially with a high GIP receptor affinity. Such a mechanism can potentiate the beneficial effect on weight loss and will therefore represent a promising target of future research. EJE Volume 192, Issue 2, February 2025 Full paper ?? https://lnkd.in/eh6wYXrR ESE Members free access via ?? https://lnkd.in/ep48a8bR #endocrinology #adipose #lipolysis #GLP1 #glucagon #obesity

Optimizing diagnostic strategies for central adrenal insufficiency in pituitary disease Authors Linus Haberbosch, Nina M T Meyer, Lara Lechner, Marie Jensen, Dominik Soll, Leonard Kozarzewski, Linus Hesse, Oliver Blankenstein, Vanessa Hubertus, Peter Vajkoczy, Christian Strasburger, Joachim Spranger, Lukas Maurer, Knut Mai EJE Volume 192, Issue 2, February 2025 Open access paper ?? https://lnkd.in/dKYy39XG Abstract Objective Central adrenal insufficiency (CAI) affects a significant number of patients with pituitary disease, and a missed diagnosis can be fatal. The optimal diagnostic algorithm, however, is still controversial. Here, we present a single-centre study with the systematic use of the overnight metyrapone test (OMT) and the short synacthen test (SST) in a large cohort of patients with pituitary disease. Methods We conducted a retrospective analysis of 161 patients with pituitary disease or after pituitary surgery and suspected CAI. Data from OMT (n = 134), SST (n = 156), and long-term clinical outcomes (n = 97) were evaluated. Results Validated in the sub-cohort with available clinical outcome evaluation after a mean of 2.7 years, 11-desoxycortisol (11-DOF, cut-off >200?nmol/L) in the OMT achieved a sensitivity of 100% and a specificity of 94%. Adrenocorticotropic hormone measurement offered no additional diagnostic benefit. Cortisol in the SST (cut-off >450?nmol/L after 30?min) showed an inferior sensitivity of 75.0% and a specificity of 80.2%. To assess the usefulness of the tests in pre-classified risk groups according to the recently proposed CAI-Score, we calculated CAI subgroup prevalence as well as positive/negative predictive value (NPV) for the SST in each risk group. In the low-risk group (CAI-Score = 0), the SST achieved a high NPV (0.99), while showing no clear benefit in the other groups. Conclusions This study reaffirms the value of 11-DOF in the OMT as a reliable diagnostic tool for CAI, while confirming the limitations of the SST. These data indicate to consider SST as a single test procedure for low-risk patients. EJE Volume 192, Issue 2, February 2025 Open access paper ?? https://lnkd.in/dKYy39XG Endo-ERN - European Reference Network Charité - Universit?tsmedizin Berlin #endocrinology #pituitary #adenoma #adrenalinsufficiency #metyrapone #hypopituitarism

Phenotype and genotype of 23 patients with hypopituitarism and pathogenic GLI2 variants Authors Karine Aouchiche, Camille Charmensat, Pertuit Morgane, Cécile Teinturier, Patricia Bretones, Aude Brac de la Perrière, Valérie Layet, Natacha Bouhours-Nouet, Marie-Christine Vantyghem, Elsa Haine, Marie-Laure Nunes-Sanchez, Odile Camard, Sabine Baron, Frederic Castinetti, Barlier Anne, BRUE Thierry, Rachel Reynaud, Alexandru Saveanu, Genhypopit Network Abstract Objective To analyze the phenotype and genotype of patients with congenital hypopituitarism (CH) and pathogenic (P) GLI2 variants. Methods A large cohort of patients with hypopituitarism was screened for GLI2 variants using a next-generation sequencing panel. Genotype–phenotype correlations were then assessed using GENHYPOPIT phenotypic data. Results Of the 39 GLI2 variants identified in 717 index cases, 17 were classified as pathogenic and likely pathogenic. All these GLI2 variants were identified in 23 patients (17 index cases and 6 relatives) with associated pituitary stalk interruption syndrome or extrapituitary manifestations. GLI2 variants were the most frequently identified genetic cause in patients with syndromic hypopituitarism (68%): 88% (15/17) of mutations were truncating variants, and 45% were de novo. Most patients with a GLI2 variant (21/23, 91%) had hypopituitarism, including 21.7% (5/23) presenting isolated growth hormone deficiency. Two patients had Kallmann syndrome. Pituitary morphological abnormalities were present in 84% of the patients with P GLI2 variants (index cases and affected relatives). The remaining signs included neurocognitive disorders (38%), hexadactyly (27%), cardiac septal defects, and renal/vesical abnormalities. A possible digenic origin (GLI2/HESX1) is proposed in one family. Conclusion In this large multicentric international cohort, GLI2 was the most frequently identified genetic cause of syndromic CH with constant association of pituitary stalk interruption syndrome or extrapituitary clinical features. In addition to polydactyly and neurocognitive disorders, cardiac and renal abnormalities were also frequently observed and should be investigated further. The variable expression of GLI2-associated phenotypes justifies further research in this area. EJE Volume 192, Issue 2, February 2025 Full paper ?? https://lnkd.in/eizyJVsy ESE Members free access via ?? https://lnkd.in/ep48a8bR #endocrinology #pituitary #hypopituitarism #cardiopathy #Kallmann

INVITED COMMENTARY Elevating endocrinology: a unified European curriculum for future specialists By FELIX BEUSCHLEIN, Editor-in-Chief "The publication of the European Society of Endocrinology (ESE) Curriculum and Training Recommendation in the European Journal of Endocrinology represents a significant milestone in standardizing postgraduate training across Europe. "This comprehensive document, developed in collaboration with the Union Européenne des Médecins Spécialistes (UEMS), provides a framework designed to enhance the quality and consistency of endocrinology training." Read more EJE Volume 191, Issue 5, November 2024 Open access ?? https://lnkd.in/ehzUXF3w

Patients with Cushing’s syndrome have elevated risk for venous thromboembolism. This position statement represents the first position statement on thromboprophylaxis for patients with endogenous Cushing’s syndrome. Prior to this, there has been a significant gap in guidance, leading to considerable heterogeneity in clinical practice. This statement was developed by a panel of 18 international experts from 11 countries and 4 continents, and provides recommendations on the initiation of thromboprophylaxis at the time of diagnosis of Cushing’s syndrome, during the peri operative period, and in case of diagnosis of venous thromboembolism (VTE). Implementing these guidelines is expected to reduce the incidence of VTE in this high risk population. The position statement will be updated every 3-5 years dependent on new evidence as it emerges. @kristina Isand #HiroshiArima Jér?me BERTHERAT Olaf Dekkers Richard Feelders Maria Fleseriu, MD,FACE #MonicaGadelha #JoseMiguelHinojosa-Amaya #NikiKaravitaki #FrederikusAKlok Ann McCormack #JohnNewell-Price Sue Pavord #Martin Reincke #Saurabh Sinha Elena Valassi #John Wass Alberto Pereira Arias European Society of Endocrinology Endo-ERN - European Reference Network The Pituitary Society Endocrine Society