Dipeptidyl Peptidase-4 Inhibition May Stimulate Progression of Carcinoid Tumor.

Vladimir Pech,Khalid Abusaada,Carlos Alemany

doi:10.1155/2015/952019

Vladimir Pech, Khalid Abusaada + Show 1 more

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https://doi.org/10.1155/2015/952019

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Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as saxagliptin, have gained a rapid growth in use in the treatment of type 2 diabetes mellitus in the past decade. Although they are considered to have a good safety profile, controversy exists regarding their potential to stimulate neoplasm growth. We report here a patient with metastatic carcinoid tumor. His disease was stable for several years with plasma serotonin level (which was used to monitor disease progression) in 700–800 ng/mL range. After initiation of treatment with saxagliptin, however, his serotonin level almost doubled (1358 ng/mL), concerning progression of the disease. After discontinuation of saxagliptin, serotonin level returned to baseline quickly, while other laboratory markers, such as complete blood count (CBC), comprehensive metabolic profile (CMP) with liver function tests (LFTs), and lactate dehydrogenase (LD), remained unchanged before, during, and after the treatment with saxagliptin. This temporal correlation suggests a possible interaction between the activity of carcinoid tumors and the use of DPP-4 inhibitors. Although we were not able to find any literature providing a direct evidence that saxagliptin alters progression of the carcinoid tumors, we recommend alternative management for the treatment of diabetes in patients with carcinoid or other neuroendocrine tumors.

Highlights

Carcinoid tumors are relatively rare neuroendocrine tumors (NET) arising from the lungs and gastrointestinal tract
We report here a 66-year-old Caucasian male patient with recurrent metastatic carcinoid tumor arising from the superior border of the third portion of the duodenum and/or inferior aspect of the pancreatic head with metastatic involvement of the mediastinal lymph nodes
Dipeptidyl peptidase-4 (DPP-4) inhibitors inhibit activity of dipeptidyl peptidase 4, an enzyme that is responsible for rapid inactivation of glucagonlike peptide 1 (GLP-1)

Summary

Introduction

Carcinoid tumors are relatively rare neuroendocrine tumors (NET) arising from the lungs and gastrointestinal tract. Their annual incidence in the United States is about 3.65 per 100,000 people [1]. The histological characteristics and clinical behavior of neuroendocrine tumors range from welldifferentiated tumors with a relatively benign clinical course to poorly differentiated neuroendocrine carcinomas that resemble small cell or large cell neuroendocrine carcinoma of the lung [2]. The term carcinoid is usually reserved for well-differentiated neuroendocrine tumors with more indolent clinical course, they do have the potential to metastasize. Treatment of metastatic carcinoid tumors that are not amenable to resection focuses on control of the symptoms of hormone hypersecretion (the serotonin syndrome) and control of the tumor growth. Most patients are managed with somatostatin analogs, such as octreotide or lanreotide, interferon alfa, and/or the molecularly targeted agents everolimus and sunitinib that have been shown to improve progressionfree survival in patients with metastases from nonfunctioning pancreatic NET [4, 5]

Case Presentation

Discussion