Glucagonoma-associated dilated cardiomyopathy refractory to somatostatin analogue therapy

Abstract

A 67-year-old woman presented with a generalised rash associated with weight loss and resting tachycardia. She had a recent diagnosis of diabetes mellitus. Biochemical evaluation revealed elevated levels of circulating glucagon and chromogranin B. Cross-sectional imaging demonstrated a pancreatic lesion and liver metastases, which were octreotide-avid. Biopsy of the liver lesion confirmed a diagnosis of well-differentiated grade 2 pancreatic neuroendocrine tumour, consistent with metastatic glucagonoma. Serial echocardiography commenced 4 years before this diagnosis demonstrated a progressive left ventricular dilatation and dysfunction in the absence of ischaemia, suggestive of glucagonoma-associated dilated cardiomyopathy. Given the severity of the cardiac impairment, surgical management was considered inappropriate and somatostatin analogue therapy was initiated, affecting clinical and biochemical improvement. Serial cross-sectional imaging demonstrated stable disease 2 years after diagnosis. Left ventricular dysfunction persisted, however, despite somatostatin analogue therapy and optimal medical management of cardiac failure. In contrast to previous reports, the case we describe demonstrates that chronic hyperglucagonaemia may lead to irreversible left ventricular compromise. Management of glucagonoma therefore requires careful and serial evaluation of cardiac status. Learning points: In rare cases, glucagonoma may present with cardiac failure as the dominant feature. Significant cardiac impairment may occur in the absence of other features of glucagonoma syndrome due to subclinical chronic hyperglucagonaemia. A diagnosis of glucagonoma should be considered in patients with non-ischaemic cardiomyopathy, particularly those with other features of glucagonoma syndrome. Cardiac impairment due to glucagonoma may not respond to somatostatin analogue therapy, even in the context of biochemical improvement. All patients with a new diagnosis of glucagonoma should be assessed clinically for evidence of cardiac failure and, if present, a baseline transthoracic echocardiogram should be performed. In the presence of cardiac impairment these patients should be managed by an experienced cardiologist.

Keywords: 2019; Adult; Alendronate; Angiotensin receptor antagonists; Angiotensin-converting enzyme inhibitors; BMI; Beta-blockers; Bisoprolol*; Bisphosphonates; Blood pressure; Brain natriuretic peptide; CD-56; CDX2*; CT scan; Calcium; Cardiomyopathy; Cardiomyopathy*; Chromogranin B*; Echocardiogram; Electrocardiogram; Endocrine-related cancer; Fatigue; Female; Furosemide; Gliclazide; Glucagon; Glucagonoma; Heart; Heart failure; Hepatic metastases; Hyperglucagonaemia; Hyperglucogonaemia; Hypotension; Lanreotide; Left ventricular ejection fraction*; Left ventricular internal diameter*; Losartan; MRI; March; Necrolytic migratory erythema; Neuroendocrine tumour; Octreotide scan; Oedema; Oncology; PAX8*; Palpitations; Pancreas; Ramipril; Rash; Somatostatin analogues; Spironolactone; Sulphonylureas; Synaptophysin; Tachycardia; Ultrasound-guided biopsy; Unique/unexpected symptoms or presentations of a disease; United Kingdom; Vitamin D; Weight loss; White.

Figure 1

Clinical and radiological features at diagnosis. (A) Representative photograph of the patient’s rash at presentation (gluteal region). (B and C) Cross-sectional imaging at presentation, showing pancreatic (B) and hepatic (C) lesions. (D) Octreotide scintigraphy showing octreotide avidity in the pancreas and liver segment VI (anterior and posterior views). (E) Gadolinium-enhanced MRI images of the pancreatic and hepatic lesions.

Figure 2

Echocardiographic features of dilated cardiomyopathy before and after somatostatin analogue therapy. Representative four-chamber views showing left ventricular dilatation at baseline (left) and after 21 months of lanreotide therapy (right).