A 55-year-old man presents to his primary care physician with fatigue, malaise, and a painful rash. The patient states that his symptoms have been worsening over the past week. He also has experienced abdominal pain and diarrhea. He has a medical history of obesity and smokes regularly. His temperature is 97.5°F (36.4°C), blood pressure is 142/82 mmHg, pulse is 85/min, respirations are 15/min, and oxygen saturation is 98% on room air. Physical exam is notable for an erythematous rash with papules and plaques on the patient's face, torso, and extremities. He states that the rash is painful. A fingerstick blood glucose is unable to accurately read his blood glucose and gives a reading of > 500 mg/dL. Which of the following is the most likely underlying pathophysiology of this patient’s condition?
Alpha cell tumor
Hypercortisolism
Beta cell destruction
Insulin resistance
Alpha cell tumor
This patient is presenting with necrolytic migratory erythema (a painful, erythematous rash with papules and plaques) with gastrointestinal symptoms (abdominal pain and diarrhea) and hyperglycemia, which are concerning for a glucagonoma. A glucagonoma is a tumor of the alpha cells.

A glucagonoma is a tumor of the alpha cells of the pancreas. This tumor pathologically secretes glucagon leading to profound hyperglycemia that is refractory to the normal treatments for diabetes. Patients also present with a classic rash termed necrolytic migratory erythema which presents with painful, erythematous papules and plaques. Other findings include gastrointestinal symptoms including anorexia, abdominal pain, and diarrhea. Hematologic findings include a normocytic, normochromic anemia. The diagnosis can be supported with a glucagon level, which will be elevated. Imaging of the pancreas by CT or MRI (more accurate) can further support the diagnosis.

Zandee et al. review glucagonoma. They note the presentation and symptoms associated with a glucagonoma, including the classic rash and elevated blood glucose. They recommend considering this diagnosis in patients who present with rash and hyperglycemia refractory to typical treatments.

Incorrect Answers:
Answer B: Beta-cell destruction is the pathophysiology of type I diabetes mellitus which presents with polydipsia, polyuria, weight loss, and hyperglycemia (typically in a pediatric patient). It can progress to diabetic ketoacidosis which presents with hyperglycemia, an anion gap acidosis, altered mental status, and Kussmaul respirations.

Answer C: Beta-cell tumor describes an insulinoma, which would present with hypoglycemia refractory to glucose administration. This condition is caused by increased release of insulin. The diagnosis should be suspected in the setting of hypoglycemia, an elevated insulin level, and an elevated C-peptide level. Imaging of the abdomen/pancreas with an MRI will reveal the insulin-secreting mass.

Answer D: Hypercortisolism can cause Cushing syndrome which presents with hyperglycemia, obesity, striae, limb/muscle atrophy, mood changes, and hypertension. A buffalo hump and moon faces may also be seen. This condition can either be from endogenous ACTH production or cortisol production or can be from exogenous steroid use.

Answer E: Insulin resistance is the pathophysiology of type 2 diabetes mellitus and presents with obesity, hyperglycemia, and an elevated hemoglobin A1c. The mainstay of management is weight loss, though medications such as metformin, sulfonylureas, or insulin are often needed.

Bullet Summary:
A glucagonoma is a tumor of the alpha cells of the pancreas that hypersecretes glucagon.