The Glucagonoma Syndrome: Clinical Features, Diagnosis, and Treatment

Abstract

Historical BackgroundIslet cell tumors of the pancreas have been described for over 50 yr. Although carcinoma arising from islet tissue had been noted since the turn of the century (1), not until 1927 was the first case of a hormonally active pancreatic neoplasm, an insulinoma, recorded (2). For many years thereafter, pancreatic endocrine tumors were characterized as either insulin-producing or "nonfunctional," the latter being derived from cells apparently devoid of clinically significant hormonal activity. With time, however, other islet cell secretory products were discovered and their tumors identified with various clinical syndromes. Whereas the hypoglycemia of insulinomas and hyperacidity of gastrinomas figured prominently in the initial recognition of these neoplasms, the clinical signs of glucagon-producing tumors were less readily apparent and not as easily attributable to specific hormone excess.Becker and co-workers (3) are credited with the first description of a glucagonoma. Their case, reported in 1947 but diagnosable only in retrospect, typifies what is now regarded as a classic clinical presentation of the syndrome. The patient, a 45-yr-old woman, sought attention because of a skin rash that, over a period of 8 months, progressed to involve almost her entire body. Weight loss, weakness, and amenorrhea were additional complaints. The rash was symmetrically distributed and characterized by confluent, pruritic areas of macular, erythematous, and vesicular erruptions showing evidence of exfoliation and superficial necrosis. Stomatitis and onchonolysis were also found. Laboratory examination revealed a normochromic anemia, mild fasting hyperglycemia, and hypoproteinemia. Deep venous thrombosis developed while the patient was in hospital, and she succumbed to cardiorespiratory failure. At autopsy, an islet cell neoplasm was discovered "replacing the body

Eritema necrolítico migratorio y glucagonoma pancreático

“…En la autopsia se encontró una neoplasia pancreática con metástasis en los ganglios linfáticos adyacentes e invasión de la glándula suprarrenal izquierda, así como trombosis de las venas cava, iliaca y femoral izquierdas (15). Las manifestaciones cutáneas fueron denominadas eritema necrolítico migratorio por Wilkinson en 1973, y Mallison, et al, introdujeron el término "síndrome de glucagonoma" para describir la asociación entre el eritema necrolítico migratorio y el glucagonoma pancreático (14,16).…”

“…Los criterios diagnósticos de un síndrome de glucagonoma comprobado fueron propuestos en 1981 (16) e incluyen los siguientes: 1) masa tumoral detectada por visualización directa o por técnicas radiográficas; 2) tumor compuesto por células que contienen glucagón; 3) niveles séricos elevados de glucagón, y 4) al menos, uno de los siguientes hallazgos: erupción cutánea, intolerancia a la glucosa e hipoaminoacidemia (16). Las manifestaciones del síndrome incluyen, además, pérdida de peso, diarrea, debilidad, trastornos neuropsiquiátricos, diabetes mellitus y cardiomiopatía dilatada (2,6,17).…”

“…Los pacientes con síndrome de glucagonoma presentan valores de glucagón sérico de entre 1.000 y 5.000 pg/ml (16). Nuestra paciente tenía 1.000 pg/ml, con un control normal de laboratorio de 50 a 100 pg/ml.…”

“…Nuestra paciente tenía 1.000 pg/ml, con un control normal de laboratorio de 50 a 100 pg/ml. Es posible que las concentraciones séricas de glucagón no se correlacionen con la edad, el sexo, las alteraciones clínicas o metabólicas, o el tamaño o la localización del tumor, ya que el potencial biológico de cada forma de glucagón depende de su peso molecular (14,16).…”

The glucagonoma syndrome and necrolytic migratory erythema: a clinical review

“…Successful palliative treatment is possible with long-acting somatostatin analogs (13) and/or interferon alpha (14). In addition, supplementation with zinc, amino acids and essential fatty acids appears to be beneficial in some cases (15 -17) together with topical dermatological therapy (10). We will now focus on the challenge of diagnosing the glucagonoma syndrome from two points of view.…”