Effect of hormone secretory syndromes on neuroendocrine tumor prognosis

Abstract

The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete a wider variety of hormones, like insulin, glucagon and gastrin leading to distinct clinical syndromes. Historically mortality in patients with functioning NETs was high due to the complications caused by the hypersecretion of hormones. This has been reduced with several drugs: protonpump inhibitors decrease acid secretion caused by gastrinomas. Somatostatin analogs can inhibit the secretion of multiple hormones and these are now the cornerstone for treating patients with a gastroenteropancreatic NET. However, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs and everolimus can also decrease symptoms of hypersecretion and increase progression-free survival. Several factors affect the survival in patients with a functioning NET. Complications of hypersecretion negatively impact survival; however, secretion of hormones is also often a sign of a well-differentiated NET and due to the symptoms, functioning NETs can be detected in an earlier stage suggesting a positive effect on prognosis. The effect on survival is also dependent on the type of hormone being secreted. This review aims to study the effect of hormone secretion on the prognosis of NETs with the contemporary treatments options available today.

Effect of A549 neuroendocrine differentiation on cytotoxic immune response

“…The mechanism for the increase in 5-HT levels is unclear, although this phenomenon has been previously observed by Mouillet-Richards in 1C11 cells ( 40 ). A possible explanation might be that dopaminergic and serotonergic cells arise from a common progenitor with a dual biogenic amine fate ( 40 ), which might explain the clinical reports of neuroendocrine tumours in serotoninergic secretion syndromes ( 41 ).…”

Clinical and Preclinical Advances in Gastroenteropancreatic Neuroendocrine Tumor Therapy

“…SSAs (octreotide, lanreotide, pasireotide) were initially developed to mimic the inhibitory action of somatostatin on cell surface G-protein-coupled receptors called SSTR1–5, which mediate downstream hormone release and cell growth via PI3K and MAPK signaling ( 19 ). These drugs are used successfully to control symptoms of the carcinoid syndrome that is clinically characterized by flushing, diarrhea and right-side heart valve disease as a result of hypersecretion of bioactive amines from small intestinal NETs ( 20 ). The ELECT trial (NCT00774930), a phase III double-blind study of lanreotide depot as a therapy for carcinoid syndrome, enrolled 115 patients—59 in the lanreotide depot arm and 56 in the placebo arm.…”

Differential Diagnosis and Management of Diarrhea in Patients with Neuroendocrine Tumors

“…Patients with GEP NETs can experience numerous and complex symptoms due to the hypersecretion of hormones and peptides such as serotonin, gastrin, insulin, glucagon [5], vasoactive intestinal peptide (VIP) [6], and pancreatic polypeptide [7], which can lead to specific hormonal hypersecretory syndromes. The most prevalent symptoms in patients with GEP NETs include diarrhea, fatigue, abdominal discomfort, flushing, and food intolerance [5].…”