Glucagonoma and the glucagonoma syndrome - cumulative experience with an elusive endocrine tumour

Abstract

Summary Objective Glucagonoma is a pancreatic neuroendocrine tumour that arises from alpha cells in the pancreas and is often accompanied by a characteristic clinical syndrome. Design In this report, we present the cumulative experience and clinical characteristics of six patients diagnosed with glucagonoma and the glucagonoma syndrome and treated at our centre during the past 25 years. Results Although the course of the disease was variable, some features were similar. The median age at diagnosis was 53·5 years; the median time from onset of symptoms to diagnosis was 39 months. Presenting symptoms were as follows: weight loss 5/6 (83%), necrotizing migratory erythema (NME) 5/6 (83%), diabetes mellitus 4/6 (66%) and diarrhoea, weakness and thrombosis 2/6 (33%). Plasma glucagon was elevated in all patients upon diagnosis (range 200–10 000 pm; N < 50). Skin biopsy was diagnostic only in 1/6 specimens obtained, even after revision. Metastatic disease developed in all patients; 4/6 initially presented with hepatic metastasis. All patient symptoms responded to somatostatin analogue therapy. In 4/6, the NME responded to amino acid solutions. Other modes of therapy were as follows: surgery in 3/6 patients, peptide receptor radioligand therapy with 90Y‐DOTATOC (PRRT) in 3/6 patients (two responses) and chemotherapy in three patients (two responded). Four out of six patients died of the disease, and median survival time was 6·25 years (range 2–11) from diagnosis and 8 years (range 8–16) from initial symptoms. Five‐year survival was 66%. Conclusion Our data indicate that somatostatin analogues and an aggressive surgical approach offer symptom relief and tumour control. Among other available treatment modalities, PRRT seems to hold the most promise.

Nutrient regulation of glucagon secretion: involvement in metabolism and diabetes

“…Although the mechanism for this failure is not clearly known, it has been suggested that the a-cell might be refractory to the insulin paracrine signal or insensitive to high glucose levels (9,15) . Patients with a glucagonoma develop hyperglucagonaemia and the characteristic hyperglycaemia of diabetes, which disappears when the tumour is removed, further suggesting that high levels of glucagon are involved in this disease (169) . Another problem of diabetes is that pancreatic a-cells do not respond adequately to hypoglycaemia, which is particularly important in insulin-treated patients, and leads to increased morbidity and mortality rates in this disease (8,23) .…”

Neuroendocrine tumor disease: an evolving landscape

“…Overall survival is w4 years and may extend to 15 years in single cases (Smith et al 1998). In a series of six patients with glucagonoma treated during a period of 25 years, Eldor et al (2011) achieved a median survival time of 6.25 years (range 2-11) from diagnosis and 8 years (range 8-16) from initial symptoms by following a multimodal treatment concept including SSAs, surgery (in three/six patients), peptide receptor radiotherapy (two responses in three/six patients), and chemotherapy (two responses in three/six patients. Ghaferi et al reported on four patients with VIPomas.…”

Glucagonoma and the glucagonoma syndrome (Review)

“…However, skin biopsies are not effective at diagnosing NME. In the 6 cases evaluated by Eldor et al (4), an evaluation of six available skin biopsies of the patients with glucagonoma indicated that only one was clearly positive for glucagonoma rash; the others exhibited only non-specific changes. NME may also present in patients without elevated glucagon level.…”

“…Surgery is currently the only method of curing glucagonoma. Somatostatin analogues (SSA) and amino acid solution infusion may result in the rapid relief of symptoms (4). Transarterial chemoembolization, radiation therapy and peptide receptor radioligand therapy may also be useful treatments (4,5).…”