Dilated cardiomyopathy, a rare and reversible manifestation of the glucagonoma syndrome

V. Antonopoulou*^a (Dr), A. Diamantopoulos^a (Dr), A. Beka^a (Dr), T. Stratigou^a (Dr), G. Kyriakopoulos^b (Dr), I. Landrou^c (Dr), P. Prigouris^c (Dr), S. Tsagarakis^a (Dr), DA. Vassiliadi^a (Dr)

^a Department of Endocrinology, Diabetes and Metabolism, National Expertise Center for Rare Endocrine Disorders and member of the Endo-ERN, “Evangelismos” General Hospital of Athens, Athens, GREECE ; ^b Pathology Department, “Evangelismos” General Hospital of Athens, Athens, GREECE ; ^c 4th Surgical Department, "Evangelismos" General Hospital of Athens, Athens, GREECE

* vasiliki.antonopoulou1@gmail.com

Introduction:Glucagonoma is a rare functional pancreatic neuroendocrine tumor associated with a characteristic syndrome due to glucagon hypersecretion.Glucagonoma-associated dilated cardiomyopathy has been reported in only a few case reports.Herein we report significant improvement of cardiac failure following surgical management in a patient with glucagonoma syndrome.

Observations:A 69-years-old female presented with glucagonoma syndrome(weight loss, diarrhea, nausea, stomatitis, necrolytic migratory erythema, normocytic anemia, recent onset diabetes and depression).She also had heart failure due to dilated cardiomyopathy(LVEF:25%, left ventricular end-diastolic dimension(LVEDD):5.9cm) without evidence for ischemia on coronary angiography.NT-proBNP levels were markedly increased(16646pg/ml), as well as levels of glucagon(2888 pg/ml), chromograninA(56nmol/l) and pancreatic polypeptide(PP) (474pmol/l). On imaging she had a 4,1cm pancreatic mass with significant uptake on 68Ga-Dotatoc-PET/CT (SUVmax:62) and in a local lymph node (SUVmax:36).Due to the severe heart failure somatostatin analogue was initially started resulting in disappearance of the necrolytic migratory erythema, but only partial clinical and biochemical response. Therefore, surgery was decided,and the patient underwent distal partial pancreatectomy, splenectomy and cholecystectomy. Histopathology demonstrated PanNET G2, ki67:12%, Glucagon(+),ChromograninA(+),Synaptophysin(+),PP(+), SSTR2a(+++) and metastasis in 3/22 local lymph nodes, pT3N1. Fifteen days after surgery, glucagon levels returned to normal(216pg/ml). LVEF mildly elevated to 30% and NT-proBNP reduced to 9444pg/ml. Two months post-surgery, further increase of LVEF was observed(45%), LVEDD decreased and NT-proBNP further dropped to 1448pg/ml. Her general condition improved, she gained weight and improved glycemic control whereas nausea and diarrhea resolved.Glucagon, chromograninA and PP levels returned to normal.

Discussion:Dilated cardiomyopathy and cardiac failure without other risk factors, such as ischemic heart disease, have been reported in only 4 patients with glucagonoma.In operated cases, as in our patient, surgical resection resulted in reversal of cardiomyopathy and LVEF improvement.On the contrary, in one patient who was treated only with somatostatin analogue heart failure persisted. Our case provides additional evidence that dilated cardiomyopathy is a rare clinical manifestation of the glucagonoma syndrome and these patients obtain substantial benefit following surgical tumor removal.

The author has declared no conflict of interest.