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Major hyperghrelinemia in advanced well-differentiated neuroendocrine carcinomas: report of three cases

¹ Hospices Civils de Lyon, Pavillon H, Hôpital Edouard Herriot, Fédération des Spécialités Digestives, 69437 Lyon Cedex 03, France² INSERM, UMR S865, IFR62, Faculté Laennec, 69372 Lyon Cedex 08, France³ Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération de Biochimie, 69437 Lyon Cedex 03, France⁴ Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d'Anatomie et Cytologie Pathologiques, 69437 Lyon Cedex 03, France⁵ Université de Lyon, Université Claude Bernard Lyon 1, 69622 Villeurbanne Cedex, France

(Correspondence should be addressed to T Walter at Hospices Civils de Lyon, Pavillon H, Hôpital Edouard Herriot, Fédération des Spécialités Digestives; Email: thomas.walter{at}chu-lyon.fr)

^* (T Walter and L Chardon contributed equally to this work)

Abstract

Objective: We aimed to gain insight into the functional consequences of ghrelin overproduction in patients with neuroendocrine tumors and its relations with disease characteristics and evolution.

Design: We retrospectively analyzed three cases of neuroendocrine carcinomas associated with very high levels of circulating ghrelin.

Methods: Between February and October 2007, serum ghrelin levels were determined in all patients with well-differentiated endocrine carcinoma referred to our center (n=72). Three patients were found to have circulating ghrelin levels >10-fold the upper limit of normal. The clinical, biochemical, and pathological characteristics of these three patients were reviewed. The ratio between circulating acyl and total ghrelin was determined, and tumor tissue expression of ghrelin was assayed by immunohistochemistry.

Results: The three patients had massive hyperghrelinemia (respectively 49 028, 63 711, and 101 996 pg/ml), with <10% of acyl ghrelin. The corresponding primary tumors were located in the pancreas, rectum, and gallbladder; all were metastatic. There was no acromegaly; there was a decrease in appetite; and body mass index was low. Serum GH levels were only slightly increased and serum IGF1 levels were normal. Immunoreactive ghrelin was detected in the tumor tissue in the two cases in which tissue material was available. All three patients died before 12 months after the diagnosis of hyperghrelinemia.

Conclusion: Well-differentiated neuroendocrine carcinomas of various origins may produce markedly high levels of circulating ghrelin, without evidence of clinical or functional consequences.