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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.

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Peptide receptor radionuclide therapy (PRRT) is used for the management of neuroendocrine tumors (NETs) not responsive to somatostatin analogs. In this case series, we report two patients with pancreatic vasoactive intestinal peptide (VIP)-secreting NETs (VIPomas) not responsive to any other therapies who achieved symptomatic control and a significant decrease in serum VIP levels with PRRT during their hospital stay. Two patients with VIPomas were admitted to the hospital with multiple prior hospital admissions after going through multiple lines of therapy.

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Evolving Immunotherapy Strategies in Gastrointestinal Neuroendocrine Neoplasms.

Curr Treat Options Oncol

January 2025

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

Treatment for neuroendocrine neoplasms (NENs) is tailored to the tumor's site of origin, grade, and differentiation. NENs are categorized into two main types: well-differentiated neuroendocrine tumors (NETs), which tend to grow more slowly and are less aggressive, and poorly differentiated neuroendocrine carcinomas (NECs), which are highly aggressive and harder to treat. Treatment options for NETs range from somatostatin analogues and mTOR inhibitors to peptide receptor radionuclide therapy (PRRT) with Lutetium-177 dotatate.

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Pasireotide (PAS), a multireceptor somatostatin analog, has been demonstrated to effectively control hormone levels, including those of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), in patients with acromegaly. However, it induces hyperglycemia by inhibiting insulin secretion via somatostatin receptor 5 (SSTR5). Despite the extensive literature on the occurrence of PAS-induced hyperglycemia, there is still no consensus on the optimal first-line treatment for this complication.

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Purpose: A paradoxical increase in GH after oral glucose load (GH-Par) characterizes about one-third of acromegaly patients and is associated with a better response to first-generation somatostatin receptor ligands (fg-SRLs). Pasireotide is typically considered as a second-/third-line treatment. Here, we investigated the predictive role of GH-Par in pasireotide response and adverse event development.

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