Glucagonoma Syndrome

A 74-year-old woman presented with a refractory pruritic eruption. Four months earlier, she had sought evaluation of a thickened, slightly crusted 6 × 8-cm patch on her right ankle of 2 months' duration. Contact dermatitis with secondary impetigo from scratching was suspected, and a topical corticosteroid and an oral antibiotic were prescribed.

Over the following months, the lesions worsened; patches and plaques of crusting erythema waxed and waned on the ankles, legs, knees, buttocks, and arms. The patient also had intermittent stomatitis that manifested as small vesicles on her tongue and hard palate. She described a burning sensation on the tongue, particularly after ingesting spicy foods. She had a 15-year history of type 2 diabetes mellitus, which was managed with insulin. Although she was thin and active, deep venous thrombosis had developed 2 months before presentation.

Red-brown crusts on an erythematous base with fissures and excoriations were noted on the ankles (A). A patch of excoriated erythema with serpenginous raised margins was also present on the buttocks (B). A 4-mm punch biopsy of the left ankle and the dorsum of the right foot revealed subacute spongiotic reaction with focal necrosis. The dermatopathologist suggested a possible acrodermatitis enteropathica or necrolytic migratory erythema associated with glucagonoma.

The serum zinc level was normal; however, the serum glucagon concentration was 522 pg/mL (normal, 20 to 100 pg/mL). A CT scan of the abdomen showed a 2.8-cm mass in the tail of the pancreas. Resection of the mass and a regional lymph node revealed islet cell carcinoma. Two days after the resection, the skin eruptions had resolved. Insulin was subsequently discontinued.

Eight months later, an octreotide scan revealed uptake in the left axilla and shoulder. The glucagon level had risen from a postresection nadir of 94 pg/mL to 284 pg/mL. The patient was treated with monthly injections of long-acting octreotide. She is currently doing well, with no skin lesions and normal glucose levels, 4 ½ years after surgery.

Glucagonomas are rare pancreatic islet cell neoplasms that are often well advanced at the time of diagnosis. Characteristic manifestations include necrolytic migratory erythema (67% to 90% of affected patients) that involves the trunk, buttocks, perineum, thighs, arms, and ankles; glucose intolerance or diabetes (40% to 90%); weight loss (66% to 90%); anemia (33% to 85%); diarrhea (15% to 29%); and venous thromboembolic events (11% to 24%).¹ Glucagonomas are usually solitary and located in the tail of the pancreas. At the time of diagnosis, more than 80% have metastasized, usually to the liver. The mean survival time for patients with metastatic glucagonoma is 59 months.²

Localized tumors without metastasis can be treated with surgery and chemotherapy, when appropriate. Early recognition of necrolytic migratory erythema in patients with hyperglycemia may lead to earlier treatment and a better prognosis.

FOR MORE INFORMATION:

• Dal Coleto CC, de Mello AP, Piquero-Casals J, et al. Necrolytic migratory erythemaassociated with glucagonoma syndrome: a case report. Rev Hosp ClinFac Med Sao Paulo. 2001;56:183-188.
• Echenique-Elizondo M, Tuneu Valls A, Elorza Ore JL, et al. Glucagonomaand pseudoglucagonoma syndrome. JOP. 2004;5:179-185.
• Marko PB, Miljkovic J, Zemljic TG. Necrolytic migratory erythema associatedwith hyperglucagonemia and neuroendocrine hepatic tumors. Acta DermatovenerolAlp Panonica Adriat. 2005;14:161-164, 166.

References:

• REFERENCES:1. Jensen RT. Glucagonoma. In: Braunwald E, Fauci AS, Kasper D, et al, eds. Harrison's Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2005:2228-2229.
  2. Radny P, Eigentler TK, Soennichsen K, et al. Metastatic glucagonoma: treatment with liver transplantation. J Am Acad Dermatol. 2006;54:344-347.