Other associated mucocutaneous findings include an atrophic glossitis, cheilosis, dystrophic nails and buccal mucosal inflammation. Although most glucagonomas appear to be sporadic, they may occur in the setting of multiple endocrine neoplasia. The glucagonoma syndrome typically manifests with very high levels of serum glucagon, up to 1000 times normal levels. However, markedly elevated levels of glucagon do not necessarily produce diabetes mellitus, NME or hypoaminoacidemia, which are the defining criteria for this syndrome. Non-neoplastic pathologies can also elevate glucagon levels high enough to produce cutaneous manifestations.
Hepatic cirrhosis is one such example.
Since the liver is responsible for glucagon breakdown, cirrhosis may prolong the effective plasma half-life of glucagon and contribute to abnormally high serum levels. This may be mediated by enteroglucagon, a substance that is produced by the crypt cells of the small intestine in the malabsorptive state. Unabsorbed nutrients in the lumen are a potent stimulator of enteroglucagon which can cause NME by an undetermined mechanism. Since glucagonoma may arise in the context of a polyfunctional endocrine tumor, it is important to assess serum glucagon in addition to serum insulin, gastrin and vasoactive intestinal peptide levels. A glucose tolerance test may help delineate the degree of glucagon excess relative to insulin.