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Malignant Gastric Ghrelinoma with Hyperghrelinemia

Department of Medical Sciences, Sections of Endocrine Oncology (A.V.T., B.K.E., K.E.O., E.T.J.) and Clinical Chemistry (M.S.), Departments of Genetics and Pathology (G.M.P.-G., L.G.) and Oncology, Clinical Immunology, and Radiology (A.S.), Uppsala University Hospital, 751 85 Uppsala, Sweden; and Centre of Nutrition (G.M.P.-G.), Lisbon University, 1649-028 Lisbon, Portugal

Address all correspondence and requests for reprints to: Apostolos V. Tsolakis, Department of Medical Sciences, Clinical Research Section 2, University Hospital, 751 85 Uppsala, Sweden. E-mail: apostolos.tsolakis{at}medsci.uu.se.

A characteristic feature of neuroendocrine tumors is production and release of peptide hormone. Ghrelin is a 28-amino acid hormone that stimulates GH release. In this paper, we describe a patient with a metastasizing gastric neuroendocrine tumor displaying intense immunoreactivity for ghrelin and extremely high circulating levels of ghrelin.

Tumor tissue biopsies from the primary tumor and one liver metastasis were examined by immunohistochemistry. Ghrelin and several other hormones and tumor markers were measured in blood. The clinical course of the patient was followed.

Tumor tissue biopsies showed immunoreactivity for cytokeratin, chromogranin A, human synaptic vesicle protein 2, synaptophysin, and ghrelin. Grossly elevated circulating levels of total ghrelin, 2100 µg/liter (reference interval < 5 µg/liter) and active ghrelin, 28 µg/liter (reference interval < 0.1 µg/liter) were found at presentation. Chromogranin A, chromogranin B, and calcitonin levels were also increased. Both total and active ghrelin increased, despite treatment, during follow-up of the patient.

We have identified and characterized a patient with a malignant gastric neuroendocrine tumor secreting ghrelin as the main hormone. This might be a new tumor entity of the stomach, and it is suggested that patients with malignant gastric neuroendocrine tumors should be investigated for ghrelin production.

This work was supported by the Swedish Cancer Society and Selanders and Lions Foundations for Cancer Research at the Uppsala University Hospital.

Abbreviations: BMI, Body mass index; IR, immunoreactive; SV2, synaptic vesicle protein 2; VMAT 2, vesicular monoamine transporter 2.

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