Diarrhea: a missed D in the 4D glucagonoma syndrome

Abstract

Glucagonoma is a rare and slow-growing pancreatic tumor that usually manifests as glucagonoma syndrome. It is mainly characterized by a typical Dermatosis named necrolytic migratory erythema (NME), Diabetes and glucagon oversecretion. Deep vein thrombosis and Depression complete this set. We report the case of an advanced glucagonoma with liver spread, where all these 4D symptoms occurred but a chronic secretory Diarrhea was the most relevant feature. A 65-year-old man was referred to our center to investigate multiple hepatic nodules evidenced by abdominal tomography. He had a recent diagnosis of diabetes and complained of significant weight loss (25 kg), crusted skin lesions and episodes of a large amount of liquid diarrhea during the past 6 months. On admission, there were erythematous plaques and crusted erosions on his face, back and limbs, plus angular cheilitis and atrophic glossitis. The typical skin manifestation promptly led dermatologists to suspect glucagonoma as the source of our patient’s symptoms. A contrast-enhanced abdominal computed tomography showed a hypervascularized pancreatic lesion and multiple hepatic nodules also hypervascularized in the arterial phase. Despite initial improvement of diarrhea after subcutaneous octreotide, the patient’s impaired nutritional status limited other therapeutic approaches and he died of respiratory failure due to sepsis. His high levels of serum glucagon were not yet available so we performed an autopsy, confirming the diagnosis of metastatic glucagonoma with NME on histology. Chronic diarrhea is not a common feature in glucagonoma syndrome; however, its severity can lead to serious nutritional impairment and set a poor outcome.

Necrolytic migratory erythema is an important visual cutaneous clue of glucagonoma

“…Glucagonoma is an extremely rare and slow-growing functional pancreatic neuroendocrine tumor arising from islet alpha cells in the tail of the pancreas. It usually presents with glucagonoma syndrome associated with characteristic clinical symptoms, including necrolytic migratory erythema (NME), diabetes mellitus (DM), stomatitis, anemia, deep vein thrombosis (DVT), weight loss, diarrhea and other symptoms 1 . With the exception of NME, other clinical manifestations are nonspecific, which accounts for the delay in diagnosis in most cases and also for the fact that at least 50% of cases already have metastatic disease at the time of diagnosis.…”

Glucagonoma: From skin lesions to the neuroendocrine component (Review)

“…Glucagonoma is a hormonally active rare neuroendocrine tumour causing an excess of glucagon (1)(2)(3). The clinical presentation is heterogeneous and it is defined as glucagonoma syndrome (GS) (1)(2)(3).…”

“…Glucagonoma is a hormonally active rare neuroendocrine tumour causing an excess of glucagon (1)(2)(3). The clinical presentation is heterogeneous and it is defined as glucagonoma syndrome (GS) (1)(2)(3). The glucagon excess is provided by a neoplasia at the level of α pancreatic cells (so called 'functional' pancreatic tumours) with a usual slow rate of growth (1)(2)(3).…”

“…The clinical presentation is heterogeneous and it is defined as glucagonoma syndrome (GS) (1)(2)(3). The glucagon excess is provided by a neoplasia at the level of α pancreatic cells (so called 'functional' pancreatic tumours) with a usual slow rate of growth (1)(2)(3). The typical skin lesion (the dermatosis) induced by a glucagonoma is a rash called necrolytic migratory erythema (NME) which is most frequently seen at disease onset (1)(2)(3).…”

“…The glucagon excess is provided by a neoplasia at the level of α pancreatic cells (so called 'functional' pancreatic tumours) with a usual slow rate of growth (1)(2)(3). The typical skin lesion (the dermatosis) induced by a glucagonoma is a rash called necrolytic migratory erythema (NME) which is most frequently seen at disease onset (1)(2)(3). Insulin-dependent diabetes mellitus, depression, diarrhoea, deep vein thrombosis are also identified, as parts of so-called 'D' syndrome (4)(5)(6).…”