What Is a Glucagonoma? Symptoms, Causes, and Treatment Options
Updated: 2 days ago
Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026
Quick Answer
A glucagonoma is a rare pancreatic neuroendocrine tumor arising from the alpha cells that make glucagon, a hormone that raises blood sugar [2] [3]. The tumor releases too much glucagon, causing glucagonoma syndrome. It is extremely rare, at roughly 0.1 to 1 new case per million people each year [3], and usually affects middle-aged and older adults [3].
Key takeaways
Primary definition: A rare pancreatic tumor that overproduces the hormone glucagon [4].
Cancer status: Usually cancerous [4]. Roughly half or more have already spread (metastasized) by the time of diagnosis [3] [6].
Hallmark symptom: Necrolytic migratory erythema (NME), a painful, blistering, migrating skin rash [1].
Common complication: Diabetes or high blood sugar caused by persistently high glucagon levels [2].
Primary treatment: Surgery for tumors confined to the pancreas [2] [3]; hormone-blocking medicines, chemotherapy, and other therapies for tumors that have spread [2].
What the research says
A rash plus diabetes should prompt a hormone test. In 21 patients with glucagonoma syndrome at the Mayo Clinic, the most common presenting symptoms were weight loss (71%), NME (67%), diabetes (38%), cheilosis or stomatitis (29%), and diarrhea (29%). The combination of NME and diabetes led to a diagnosis in about 7 months, compared with about 4 years when either appeared alone, and all 21 patients already had metastatic disease at presentation (Wermers et al., Medicine (Baltimore), 1996) [7].
In recent cases the rash is almost universal, and about half have spread. A review of 86 cases reported since 2017 found NME in 93.2% (69 of 74 with data), diabetes in 70.3%, weight loss in 62.2%, anemia in 44.6%, and glossitis, stomatitis or cheilitis in 31.1%. Metastasis was detected in 52.3% of patients (45 of 86), and compared with older series the diagnosis was made at an earlier age with a higher rate of NME, consistent with better diagnostic accuracy (Anelli et al., Clin Endocrinol, 2025) [6].
Treatment can control the disease for years. In a Swedish referral center, glucagonoma made up about 7% of 340 patients with endocrine pancreatic tumors. Among 23 patients with malignant glucagon-secreting tumors, 78% had liver metastases at diagnosis, and streptozotocin plus 5-fluorouracil chemotherapy produced objective radiological responses in 50% of evaluable patients. During the study, 11 patients died at a median of 80 months from diagnosis, while 11 were alive after a median follow-up of 52 months (Kindmark et al., Med Oncol, 2007) [8].
Understanding Glucagonoma Syndrome
The overproduction of glucagon by the tumor disrupts the body's metabolic balance. Glucagon normally works against insulin, helping keep blood sugar from dropping too low. When glucagon stays high because of a tumor, blood sugar stays high and the body breaks down protein and fat, which leads to weight loss and low levels of amino acids and other nutrients.
Prevalence and Demographics
Glucagonomas are among the rarest forms of pancreatic tumors.
Incidence: Roughly 0.1 to 1 new case per million people each year [3].
Age group: Usually diagnosed in middle-aged and older adults, most often between about 40 and 70 [3]. The average age was about 48 in a recent review of 86 cases [6].
Location: Most of these tumors are found in the tail or body of the pancreas [1] [3].
Common Signs and Symptoms
The most recognizable sign of a glucagonoma is a specific type of skin rash, but the syndrome can affect the skin, mouth, metabolism, digestion, blood vessels, and mood.
Symptom category | Specific sign | What it looks or feels like |
Skin | NME rash | A painful, itchy, red rash that blisters and moves around the body [1]. |
Mouth and face | Glossitis and cheilitis | |
Metabolic | High blood sugar or diabetes | Increased thirst, frequent urination, and increased hunger [4]. |
Weight | Weight loss | Unintended, often marked, weight loss [3]. |
Blood | Anemia [3] | Tiredness and paleness from a low red blood cell count. |
Digestive | Chronic diarrhea [3] | Persistent loose stools that can lead to dehydration. |
Vascular | Blood clots | A higher risk of deep vein thrombosis (DVT) in the legs [3]. |
Mood and thinking | Neuropsychiatric changes | Depression, irritability, or slowed thinking [3]. |
The Glucagonoma Rash (NME)
Necrolytic migratory erythema (NME) is the most characteristic feature of the syndrome [2]. It was reported in 93.2% of 74 recent cases with data [6]. It may affect any site, but it most often involves the genital and anal region, buttocks, groin, and lower legs, and its severity comes and goes [1]. It typically begins as a ring-shaped red area that blisters, erodes, and crusts over [1]. It can be itchy and painful, and as it heals it may leave a brown mark [1].
Causes and Risk Factors
In most cases the cause of a glucagonoma is unknown [4] [5]. A genetic link exists in a minority of patients.
Genetic predisposition: About 10% of cases arise in the setting of inherited tumor syndromes [9], most notably multiple endocrine neoplasia type 1 (MEN1), an inherited condition that causes tumors in several endocrine glands. Some sources estimate up to about 20% [3] (Marini et al., Endocr Relat Cancer, 2024).
Cellular origin: The tumor always begins in the alpha cells of the pancreatic islets, the body's natural glucagon producers [3].
Diagnosis and Testing
Because the symptoms can mimic common diabetes or skin conditions such as eczema, specific tests are needed to confirm the tumor and the excess hormone.
Test type | What it shows |
Fasting glucagon | Usually above 500 pg/mL (normal is under about 150 pg/mL; lab ranges vary) [3]. |
Fasting blood sugar | Elevated, reflecting diabetes caused by excess glucagon [5]. |
Amino acid and zinc levels | Low amino acids (hypoaminoacidemia) and low zinc are common [3]. |
Complete blood count | May show anemia [3]. |
Skin biopsy | Helps confirm the NME rash [3]. |
Imaging (CT or MRI) | Shows the location and size of the tumor and any spread to the liver [3]. |
Endoscopic ultrasound | A high-resolution view of the pancreas and nearby lymph nodes. |
Somatostatin receptor imaging | An octreotide scan or DOTATATE PET scan helps locate the tumor and small areas of spread [3]. |
Genetic testing |
Treatment and Management Options
Treatment has two parts: managing the effects of excess hormone and treating the tumor itself.
Symptom Management
Before or alongside tumor-directed therapy, the care team works to stabilize the person's health:
Hormone-blocking injections: Long-acting octreotide or lanreotide reduce glucagon release, can ease the rash and other symptoms, and are first-line treatment for functioning glucagonomas [2] [3].
Nutritional support: Amino acid and zinc supplements, and sometimes total parenteral nutrition (TPN, feeding through a vein), to reverse malnutrition and help the rash [3].
Diabetes care: Insulin or oral medicines to control blood sugar [5].
Clot prevention: Blood thinners such as heparin to prevent deep vein thrombosis, especially around surgery [3].
Tumor-Directed Therapy
Surgery: The main treatment and the only potentially curative option for a tumor confined to the pancreas [3] [5]. If the tumor is completely removed, symptoms usually resolve as hormone levels fall [2] [5].
Treatment for tumors that have spread: When the cancer has spread, usually to the liver, options include chemotherapy, targeted drugs such as sunitinib or everolimus, peptide receptor radionuclide therapy, and liver-directed treatments such as radiofrequency ablation (using heat to destroy tumor cells) or chemoembolization (blocking the tumor's blood supply) [2] [3].
Outlook and Recovery
The outlook depends heavily on whether the tumor has spread. Glucagonomas usually grow slowly, so some people live for years even after the tumor has spread, but a cure is rare once it has [3]. MedlinePlus reports a 5-year survival rate of about 85% when the tumor is confined to the pancreas and surgery is successful [4]. When a localized tumor is removed, symptoms typically resolve as hormone levels return to normal [5]. Regular follow-up with blood tests and imaging is used to watch for recurrence [3] [5].
Conclusion
Glucagonoma is a rare and complex condition that needs a team approach to care. Recognizing the hallmark NME rash together with new diabetes-like symptoms and unexplained weight loss can prompt earlier testing, which gives the best chance of finding the tumor before it spreads. With modern hormone-blocking medicines, surgery, and other therapies, the symptoms of glucagonoma syndrome can be controlled and, in some cases, the tumor can be removed or cured.
Frequently Asked Questions
Is glucagonoma always cancerous?
Most glucagonomas are cancerous (malignant). In many cases the tumor has already spread, most often to the liver, by the time it is diagnosed.
What organ does glucagonoma affect most?
It starts in the pancreas but frequently spreads to the liver.
What is the "hallmark" symptom of glucagonoma?
The most distinctive symptom is a migrating, painful skin rash called necrolytic migratory erythema (NME).
Can glucagonoma cause diabetes?
Yes. The excess glucagon raises blood sugar and can lead to diabetes.
How rare is this condition?
It is extremely rare, with roughly 0.1 to 1 new case per million people each year.
What age group is most at risk?
It is usually diagnosed in middle-aged and older adults, most often between about 40 and 70 years of age.
Is glucagonoma hereditary?
Usually not. About 10% of cases arise with inherited tumor syndromes, most notably multiple endocrine neoplasia type 1 (MEN1), and some sources estimate up to about 20%.
What hormone does the tumor produce?
It produces glucagon, which normally raises blood sugar.
Can surgery cure glucagonoma?
Surgery is the only potentially curative treatment. It can cure the tumor when it is confined to the pancreas and completely removed, but only a minority of people are cured because many tumors have already spread.
What is octreotide used for in this condition?
It is a medication that reduces the release of excess glucagon and can help ease the rash and other symptoms.
Why does glucagonoma cause weight loss?
High glucagon levels promote the breakdown of protein and fat in the body.
Can the rash be mistaken for something else?
Yes. It can be mistaken for other skin conditions such as eczema or psoriasis before the tumor is found.
What are "alpha cells"?
These are the cells in the pancreas that naturally make glucagon. They are the source of the tumor.
Does glucagonoma cause diarrhea?
Yes. Chronic diarrhea is a common symptom of the syndrome.
What imaging is best for finding the tumor?
CT scans, MRI, and endoscopic ultrasound are all commonly used, and somatostatin receptor imaging can help find the tumor and small areas of spread.
What is the normal level of glucagon?
Normal fasting levels are generally under about 150 pg/mL, while glucagonoma levels are usually above 500 pg/mL. Lab ranges vary.
Can glucagonoma cause blood clots?
Yes. People with the syndrome have a higher risk of deep vein thrombosis (DVT).
Are there psychiatric symptoms?
Yes. Depression, irritability, and slowed thinking or cognitive decline can occur.
What is NME?
Necrolytic migratory erythema, the medical name for the glucagonoma rash.
Can I live a normal life with glucagonoma?
Some people manage the condition for years with medication and other treatments, even if the tumor has spread.
Does the tumor grow fast?
No. Glucagonomas usually grow slowly.
What is the tail of the pancreas?
It is the narrow end of the pancreas, where most glucagonomas are found.
Why do patients need zinc supplements?
Low zinc levels may contribute to the NME rash, and zinc supplements can help clear it in some patients.
Can chemotherapy help?
Yes. It is used for tumors that have spread beyond the pancreas or are growing quickly.
What is hypoaminoacidemia?
A condition of low amino acids in the blood, which is common in people with glucagonoma.
Is there a blood test for this?
Yes. A fasting glucagon blood test is the main diagnostic blood test.
Can glucagonoma cause hair loss?
Hair thinning and brittle nails can occur, usually as a result of malnutrition.
What is radiofrequency ablation?
A treatment that uses heat to destroy tumor cells, often in the liver.
Where does the rash usually appear?
It can appear anywhere, but it is most common in the genital and anal area, buttocks, groin, and lower legs.
What is an "islet cell tumor"?
Another name for a neuroendocrine tumor that starts in the hormone-producing cells of the pancreas.
Does glucagonoma increase hunger?
It can. Like diabetes, it may cause increased appetite.
Can it cause a sore tongue?
Yes. Glossitis (a smooth, red, sore tongue) is a frequent symptom.
What is MEN1?
Multiple endocrine neoplasia type 1, an inherited syndrome that causes tumors in several hormone glands.
How is the diabetes managed?
With insulin injections or oral diabetes medicines, guided by the care team.
What is chemoembolization?
A procedure that delivers chemotherapy directly to a tumor while blocking its blood supply.
Can glucagonoma be prevented?
There is no known way to prevent it, because the cause is usually unknown.
Is it more common in men or women?
Both men and women are affected.
What is the survival rate?
It depends mainly on whether the tumor has spread. MedlinePlus reports a 5-year survival rate of about 85% when the tumor is confined to the pancreas and surgery is successful.
Can the rash move?
Yes. The "migratory" in NME means the rash moves to different parts of the body.
Does glucagonoma affect the liver?
The liver is the most common site where the tumor spreads.
What is TPN?
Total parenteral nutrition, which is feeding through a vein. It is used for severe malnutrition in glucagonoma.
Can the tumor be seen on a regular ultrasound?
Sometimes, but CT, MRI, or endoscopic ultrasound usually give a clearer picture.
Are there any specific diet tips?
Nutritional support, including amino acid and zinc supplements, is often recommended. A dietitian on the care team can tailor a plan.
What is a "counter-regulatory" hormone?
A hormone, like glucagon, that works against the effects of insulin.
Can glucagonoma cause thirst?
Yes. Excessive thirst (polydipsia) is a symptom of high blood sugar.
What happens if it's left untreated?
It can lead to severe malnutrition, life-threatening blood clots, and spread of the cancer.
Can children get glucagonoma?
It is extremely rare in children. Most cases occur in adults.
Is the rash painful?
Yes. It is usually both painful and itchy.
What is "glucagonoma syndrome"?
The group of symptoms (rash, high blood sugar, weight loss, and more) caused by the tumor's excess glucagon.
Who treats this condition?
Usually a team that includes endocrinologists, oncologists, and surgeons.
References
Oakley A. Necrolytic migratory erythema (glucagonoma syndrome). DermNet. Page last modified May 23, 2024. https://dermnetnz.org/topics/necrolytic-migratory-erythema
Evers BM. Glucagonoma. Merck Manual Professional Version. Full review May 2026; last updated October 2026. https://www.merckmanuals.com/professional/oncology/gastrointestinal-and-pancreatic-neuroendocrine-tumors-nets/glucagonoma
Menon G, Jialal I. Glucagonoma. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Last update May 3, 2025. PMID: 30137784. https://www.ncbi.nlm.nih.gov/books/NBK519500/
MedlinePlus. Glucagonoma. MedlinePlus, National Library of Medicine. Updated by Dhaliwal SK; review date October 1, 2024. https://medlineplus.gov/ency/article/000326.htm
Society for Endocrinology. Glucagonoma. You and Your Hormones. Last reviewed November 2021. https://www.yourhormones.info/endocrine-conditions/glucagonoma/
Anelli S, Mazzilli R, Zamponi V, et al. Glucagonoma and glucagonoma syndrome: an updated review. Clin Endocrinol (Oxf). 2025;103(4):417-426. PMID: 40613421. https://doi.org/10.1111/cen.15300
Wermers RA, Fatourechi V, Wynne AG, et al. The glucagonoma syndrome. Clinical and pathologic features in 21 patients. Medicine (Baltimore). 1996;75(2):53-63. PMID: 8606627. https://doi.org/10.1097/00005792-199603000-00002
Kindmark H, Sundin A, Granberg D, et al. Endocrine pancreatic tumors with glucagon hypersecretion: a retrospective study of 23 cases during 20 years. Med Oncol. 2007;24(3):330-337. PMID: 17873310. https://doi.org/10.1007/s12032-007-0011-2
Marini F, Giusti F, Brandi ML. Genetic disorders and insulinoma/glucagonoma. Endocr Relat Cancer. 2024;31(5):e230245. PMID: 38552306. https://doi.org/10.1530/ERC-23-0245
Medical disclaimer
This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions about a medical condition or before making decisions about treatment. Never disregard professional medical advice or delay seeking it because of something you have read here.
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