Glucagonoma maligno como causa infrecuente de diabetes de inicio Malignant glucagonoma: an uncommon cause of new onset diabetes

A 44-year-old female patient was initially seen at the endocrinology department for hyperglycemia (random blood glucose level of 580 mg/dL and glycosylated hemoglobin of 10.3%) associated with weight loss, cardinal clinical signs, and severe asthenia. Basal-bolus insulin therapy was started because of the presence of clinical signs of insulinopenia. two weeks later, the patient started to experience erythematous-desquamative plaque-like lesions in the skin of the upper and lower limbs. the lesions progressively enlarged, were coalescent, and had a patchy distribution. they gradually regressed and cleared at their centres. Other periorificial erythematous and crusty lesions (perinasal, peribuccal, and perianal), severe glossitis, nail dystrophy, progressive alopecia, and blepharitis were also observed. the patient also showed a significantly impaired general condition and mood with progressive weight loss and severe anorexia. She was therefore admitted for a complete work-up. initial laboratory tests showed normocytic and no rmoch rom i c anem ia ( hemog l ob i n 10 g/dL ) , hypoproteinemia with hypoalbuminemia (total protein 5.6 g/dL [normal range (Nr): 6.5-8 g/dL] and albumin 2.9 g/ dL [Nr: 3.5-5.3 g/dL]), and decreased plasma zinc levels (46.9 μg/dL; Nr: 70-120 μg/dL). A vulvar tissue biopsy was reported as a skin fragment with a neutrophilic pustule with focal parakeratosis, acanthosis, and a perivascular mixed inflammatory infiltrate suggesting necrolytic migratory erythema (NME). Based on the presence of these lesions together with diabetes mellitus and the systemic picture, glucagon and chromogranin A levels were measured. High glucagon levels were found in two measurements (510 and 655 pg/mL; Nr: 59-177 pg/mL), and a high chromogranin A value was also measured (798.8 ng/mL, Nr: 19.4-98.1 ng/ mL). Glucagonoma was suspected, based on clinical and biochemical evidence, and imaging tests were performed to locate the lesion. in these tests (including helical computed tomography [ct] of the abdomen, cholangio-Mri, and echoendoscopy in chronological order), no tumor lesions were seen in the pancreas or in other locations. in order to locate the lesion, a scan was performed using 111in-DtPA-DPhe-octreotide (Octreoscan®). this showed a large hyperuptake site of the tracer in the epigastrium midline corresponding to the pancreatic anatomical area, and an additional, less intense accumulation of the radioactive drug in the hepatic border (fig. 1). treatment was started with octreotide 50 μg daily by the subcutaneous route every 12 hours for two weeks, and every 8 hours thereafter. this treatment was well tolerated and induced a clinical improvement in the patient, with the virtual disappearance of skin lesions and a marked decrease in insulin requirements. Pancreatic glucagonoma was diagnosed, and surgery was performed. intraoperative examination confirmed the presence of a large lesion involving the body and tail of the pancreas. Laparoscopic corporocaudal pancreatectomy was performed, and the liver surface was examined by intraoperative ultrasound, which showed no lesions. the surgical specimen weighed 46 g and was 8.5 x 4.5 cm in size. A pathological study revealed a disorganized parenchyma with multiple confluent nodules. Necrosis, multiple vascular invasions, and infiltration of peripancreatic soft tissue and resection margins were seen by light microscopy. immunohistochemica l s ta in ing was pos i t ive for neuroendocrine differentiat ion markers such as chromogranin and cD56, and for glucagon as a specific hormone marker. the Ki-67 index was 5%-10%. the pathological diagnosis was a multifocal and histologically malignant endocrine tumor consistent with glucagonoma (fig. 2). After surgery, octreotide treatment was discontinued, skin and mucosal lesions disappeared completely, and insulin administration was not required. Supplemental tests performed after surgery revealed the disappearance of the hyperuptake site of the tracer located in the epigastrium midline, and no other pathological uptake was seen (Octreoscan®). Abdominal Mri after surgery showed no lesions suggesting metastases or signs of locoregional recurrence. chromogranin A levels decreased after surgery, but remained high (577 ng/mL), and glucagon levels returned to normal (71 pg/mL). A genetic study was requested in order to rule out the possibility that the glucagonoma occurred in the setting of multiple endocrine neoplasia type 1 (MEN 1). Mercedes Molinaa, Javier Garcíaa, Miguel c f t. reala, rafael carmenaa,*