Glucagonoma

Glucagonoma is an exceptionally rare tumour of the pancreatic alpha cells, leading to an overproduction of the hormone glucagon. It is typically associated with necrolytic migratory erythema, weight loss, and mild diabetes mellitus. Most cases occur spontaneously, but around 10% are linked to multiple endocrine neoplasia type 1 (MEN-1) syndrome.

Causes

The precise cause of glucagonoma remains unknown. However, genetic factors may play a role. A family history of MEN-1 is a notable risk factor, as is Mahvash disease, which involves a mutation in the glucagon receptor gene (GCGR).

Mechanism

Glucagonoma arises from the overproduction of glucagon, a peptide hormone produced by pancreatic alpha cells. This results in several classic symptoms:

• Necrolytic Migratory Erythema (NME): Occurs in about 70% of cases, presenting as erythematous lesions over the distal extremities and groin area.
• Weight Loss: The most commonly associated effect, resulting from glucagon's inhibitory effect on glucose uptake by somatic cells.
• Diabetes Mellitus: Frequently occurs due to the imbalance between insulin and glucagon, although not present in all cases.

Interestingly, people with Mahvash disease who develop glucagonoma do not exhibit NME, suggesting that functional glucagon receptors are necessary for NME manifestation.

Diagnosis

Diagnosing glucagonoma involves identifying glucagonoma syndrome symptoms and elevated glucagon levels in the blood. A confirmed diagnosis is established when blood glucagon concentration exceeds 500 mg/mL alongside glucagonoma syndrome. It is very important to note that hyperglucagonaemia alone does not confirm glucagonoma, as elevated glucagon levels can also be associated with other conditions like pancreatitis and kidney failure.

Statistically, around 60% of diagnosed individuals are women, primarily within the age range of 45–60 years.

Treatment

Sporadic glucagonoma often leads to higher mortality rates compared to those associated with MEN1, as the latter group undergoes regular medical check-ups. Metastatic tumours pose significant treatment challenges due to their resistance to chemotherapy. Surgical intervention remains the only curative therapy, though it is not always successful.

To manage heightened glucagon secretion, octreotide, a somatostatin analogue, can be administered to inhibit glucagon release. Additionally, doxorubicin and streptozotocin have been used to selectively damage pancreatic alpha cells, thereby minimising symptom progression without destroying the tumour.

History

Since the first description by Becker in 1942, fewer than 251 cases of glucagonoma have been documented. Given its rarity (less than one in 20 million worldwide), long-term survival rates are not well established. Glucagonoma accounts for approximately 1% of neuroendocrine tumours, although this figure may be underestimated due to the non-specific nature of its symptoms.

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Self-assessment MCQs (single best answer)

What type of cells does glucagonoma originate from?

Which syndrome is glucagonoma often associated with?

What is the hallmark skin condition associated with glucagonoma?

What is the primary hormone overproduced in glucagonoma?

Which metabolic condition is commonly associated with glucagonoma?

Which genetic disease involves a mutation in the glucagon receptor gene and is a risk factor for glucagonoma?

What diagnostic criterion is essential to confirm glucagonoma?

What is the main treatment for sporadic glucagonoma?

Which medication can be used to inhibit glucagon release in glucagonoma patients?

What percentage of glucagonoma cases are typically associated with necrolytic migratory erythema (NME)?