Why does glucagonoma cause weight loss?

From the Guidelines

Glucagonoma causes weight loss primarily due to the excessive production of glucagon, leading to a catabolic state, increased gluconeogenesis, and lipolysis, as well as poor nutrient absorption and decreased appetite. This is evident from the clinical features of pancreatic neuroendocrine tumors, including glucagonoma, which presents with symptoms such as weight loss, diabetes mellitus, stomatitis, and diarrhea 1. The metabolic derangements caused by excess glucagon result in significant tissue breakdown, particularly affecting muscle and fat tissues.

Some key points to consider in the management of glucagonoma-related weight loss include:

• The use of octreotide, which can help manage symptoms of hormonal excess, including those associated with glucagonoma 1
• The potential need for total parenteral nutrition (TPN) to address severe weight loss, as mentioned in the context of preoperative management for pancreatic neuroendocrine tumors 1
• The importance of addressing the underlying tumor, as complete resection can lead to more favorable outcomes, even in the presence of liver metastases 1

The pathophysiology of glucagonoma-induced weight loss involves:

• Increased breakdown of stored glycogen in the liver, converting it to glucose and releasing it into the bloodstream
• Promotion of gluconeogenesis, creating new glucose from non-carbohydrate sources like amino acids from muscle protein
• Increased lipolysis, breaking down fat stores for energy
• Poor nutrient absorption due to conditions like necrolytic migratory erythema
• Decreased appetite, nausea, and diarrhea, further contributing to inadequate nutritional intake

Overall, the management of weight loss in glucagonoma requires a comprehensive approach, addressing both the underlying metabolic derangements and the nutritional deficiencies that arise from the tumor's effects on the body.

From the Research

Glucagonoma and Weight Loss

• Glucagonoma is a rare pancreatic neuroendocrine tumor that can cause a range of symptoms, including weight loss 2, 3, 4.
• Weight loss is a common presenting symptom of glucagonoma, occurring in 71-83% of patients 2, 3.
• The exact mechanism of weight loss in glucagonoma is not fully understood, but it is thought to be related to the high levels of glucagon produced by the tumor 5, 4.
• Glucagon can induce hypoaminoacidemia, which may contribute to weight loss and other symptoms such as necrolytic migratory erythema 4.

Treatment and Management

• Somatostatin analogues, such as octreotide, can alleviate symptoms of glucagonoma, including weight loss, by reducing glucagon production 2, 5.
• However, octreotide may not prevent tumor growth, and other treatment modalities, such as surgery and chemotherapy, may be necessary to control the disease 2, 5.
• Calcium infusion may inhibit the suppressive effects of octreotide on glucagon and insulin secretion, which could impact treatment strategies 6.

Clinical Characteristics

• The glucagonoma syndrome is characterized by a range of clinical features, including necrolytic migratory erythema, diabetes mellitus, weight loss, and diarrhea 2, 3, 4.
• The diagnosis of glucagonoma is often delayed, and patients may present with advanced disease, making treatment more challenging 2, 3.