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Differential Impact of Medical Therapies for Acromegaly on Glucose Metabolism.
Int J Mol Sci
January 2025
Endocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, 16132 Genova, Italy.
Acromegaly is a rare endocrine disorder caused by excessive growth hormone (GH) production, due, in the vast majority of cases, to the presence of a GH-secreting pituitary tumour. The chronic elevation of GH and the resulting high circulating levels of insulin-like growth factor-1 (IGF-1) cause the characteristic tissue overgrowth and a number of associated comorbidities, including several metabolic changes, such as glucose intolerance and overt diabetes mellitus (DM). Elevated GH concentrations directly attenuate insulin signalling and stimulate lipolysis, decreasing glucose uptake in peripheral tissues, thus leading to the development of impaired glucose tolerance and DM.
View Article and Find Full Text PDFEfficacy of cartilage-targeted IGF-1 in a mouse model of growth hormone insensitivity.
Front Endocrinol (Lausanne)
January 2025
Section on Growth and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health, Bethesda, MD, United States.
Recombinant human IGF-1 is used to treat severe primary IGF-1 deficiency, but this treatment requires twice-daily injection, often does not fully correct the growth deficit, and has important off-target effects. We therefore sought to target IGF-1 to growth plate cartilage by generating fusion proteins combining IGF-1 with single-chain human antibody fragments that target matrilin-3, a cartilage matrix protein. We previously showed that this cartilage-targeting IGF-1 fusion protein (CV1574-1) promoted growth plate function in a GH-deficient (lit) mouse model.
View Article and Find Full Text PDFReal-Life Data on the Safety of Pasireotide in Acromegaly: Insights from EudraVigilance.
Pharmaceuticals (Basel)
December 2024
Preclinical Department, Faculty of Medicine, "Lucian Blaga" University of Sibiu, 550169 Sibiu, Romania.
Background/objectives: Pasireotide (PAS) is a somatostatin receptor ligand (SRL) used to treat acromegaly, a chronic condition caused by excess growth hormone. While it offers significant benefits as a second-line treatment for uncontrolled acromegaly, its use raises major concerns due to hyperglycemic side effects and gastrointestinal issues, the latter being similar to those seen with first-generation SRLs. The aim of this study is to evaluate the real-world evidence on adverse drug reactions (ADRs) reported for PAS in the EudraVigilance database, in comparison to other established drug-based therapies for acromegaly.
View Article and Find Full Text PDFAcromegaly: diagnostic challenges and individualized treatment.
Expert Rev Endocrinol Metab
January 2025
Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
Introduction: Acromegaly is due in almost all cases to a GH-secreting pituitary tumor. GH and IGF-1 excesses lead to its multi-system clinical manifestations and comorbidities. Acromegaly is under-diagnosed and typically presents with advanced disease.
View Article and Find Full Text PDFGH receptor polymorphisms guide second-line therapies to prevent acromegaly skeletal fragility: preliminary results of a pilot study.
Front Endocrinol (Lausanne)
September 2024
Dipartimento di Medicina Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
Background: Skeletal fragility is characterized by increased frequency of vertebral fractures (VFs) in acromegaly. Several trials were conducted to identify modifiable risk factors and predictors of VFs, with limited data on the prognostic role of GH receptor (GHR) isoforms. In this study, we investigated the potential role of GHR polymorphism on the occurrence of incidental VFs (i-VFs), in patients treated with second-line medical therapies.
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