Glucagonoma overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2]
Overview
A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in up to a 1000-fold overproduction of the hormone glucagon. Alpha cell tumors are commonly associated with glucagonoma syndrome, though similar symptoms are present in cases of pseudoglucagonoma syndrome in the absence of a glucagon-secreting tumor. Glucagonoma was first described in 1942 by Becker. In 1966 McGavran was first to report a case with hyperglucagonemia associated with cutaneous changes. In 1970, Wilkinson described the typical skin eruption in glucagonoma as necrolytic migratory erythema.[1][2] On microscopic histopathological analysis, findings of glucagonoma are epidermal necrosis, subcorneal pustules, either isolated or associated with necrosis of the epidermis, confluent parakeratosis, epidermal hyperplasia, and marked papillary dermal angioplasia and suppurative folliculitis. Glucagonoma must be differentiated from certain skin lesions (acrodermatitis enteropathica, psoriasis, pellagra, eczema) and other causes of hyperglucagonemia (infection, diabetes mellitus, Cushing syndrome, renal failure, acute pancreatitis, severe stress, and prolonged fasting). The incidence of glucagonoma is approximately 1 per 20,000,000 individuals worldwide.[3] Glucagonoma affects men and women equally. The median age at diagnosis of glucagonoma is 52.5 years. Common risk factors in the development of glucagonoma include positive family history of multiple endocrine neoplasia type 1.[2][4] If left untreated, patients with glucagonoma may progress to develop necrolytic migratory erythema, cheilosis, stomatitis, diarrhea, polyuria, and polydipsia.The presence of metastasis is associated with a particularly poor prognosis among patients with glucagonoma. The 10 year event free survival rate is less than 51.6% with metastasis and 64.3% without metastasis. According to The American Joint Committee on Cancer (AJCC), there are four stages of glucagonoma based on the TNM staging sysytem.[5] Symptoms of glucagonoma include necrolytic migratory erythema, cheilosis, stomatitis, diarrhea, polyuria, and polydipsia. A positive family history of multiple endocrine neoplasia type 1 may be present. Common physical examination findings of glucagonoma include tachycardia, fever, rash, muscle atrophy, cotton wool spots, flame hemorrhage, and dot and blot hemorrhage on fundoscopic examination of the eye may be present. Laboratory findings consistent with the diagnosis of glucagonoma include serum glucagon concentration of 1000pg/ml or greater.[6][7] Findings on abdominal CT scan suggestive of glucagonoma include reinforced mass in the arterial phase of the enhanced CT scan.[8] Abdominal MRI is helpful in the diagnosis of glucagonoma. On abdominal MRI, glucagonoma is characterized by a mass which is hypointense on T1-weighted MRI and hyperintense on T2-weighted MRI.[8] Abdominal ultrasound scan may be helpful in the diagnosis of glucagonoma. Findings on ultrasound scan suggestive of glucagonoma is hypoechoic tumor in the distal pancreas.[9] Other imaging studies for glucagonoma include positron emission tomography scan and somatostation receptor scintigraphy. Other diagnostic study for glucagonoma includes biopsy, which demonstrates epidermal necrosis, subcorneal pustules, either isolated or associated with necrosis of the epidermis, confluent parakeratosis, epidermal hyperplasia, and marked papillary dermal angioplasia and suppurative folliculitis. The predominant therapy for glucagonoma is surgical resection. Adjunctive chemotherapy may be required. Surgery is the mainstay of treatment for glucagonoma. The feasibility of surgery depends on the stage of glucagonoma at diagnosis.[6] Secondary prevention measures of glucagonoma include routine glucagon levels and imaging at scheduled intervals after treatment.[10]
==Historical Perspective==
Glucagonoma was first described in 1942 by Becker. In 1966 McGavran was first to report a case with hyperglucagonemia associated with cutaneous changes. In 1970, Wilkinson described the typical skin eruption in glucagonoma as necrolytic migratory erythema.[1][2] The predominant therapy for glucagonoma is surgical resection. Adjunctive chemotherapy may be required.
Pathophysiology
On microscopic histopathological analysis, findings of glucagonoma are epidermal necrosis, subcorneal pustules, either isolated or associated with necrosis of the epidermis, confluent parakeratosis, epidermal hyperplasia, and marked papillary dermal angioplasia and suppurative folliculitis.
Causes
There are no established causes for glucagonoma.[4]
Differential Diagnosis
Glucagonoma must be differentiated from certain skin lesions (acrodermatitis enteropathica, psoriasis, pellagra, eczema) and other causes of hyperglucagonemia (infection, diabetes mellitus, Cushing syndrome, renal failure, acute pancreatitis, severe stress, and prolonged fasting).
Epidemiology and Demographics
The incidence of glucagonoma is approximately 1 per 20,000,000 individuals worldwide.[3] Glucagonoma affects men and women equally. The median age at diagnosis of glucagonoma is 52.5 years.
Risk Factors
Common risk factors in the development of glucagonoma include positive family history of multiple endocrine neoplasia type 1.[2][4]
Screening
According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for glucagonoma.[11]
Natural History, Complications and Prognosis
If left untreated, patients with glucagonoma may progress to develop necrolytic migratory erythema, cheilosis, stomatitis, diarrhea, polyuria, and polydipsia.The presence of metastasis is associated with a particularly poor prognosis among patients with glucagonoma. The 10 year event free survival rate is less than 51.6% with metastasis and 64.3% without metastasis.
Staging
According to The American Joint Committee on Cancer (AJCC), there are four stages of glucagonoma based on the TNM staging sysytem.[5]
History and Symptoms
Symptoms of glucagonoma include necrolytic migratory erythema, cheilosis, stomatitis, diarrhea, polyuria, and polydipsia. A positive family history of multiple endocrine neoplasia type 1 may be present.
Physical Examination
Common physical examination findings of glucagonoma include tachycardia, fever, rash, muscle atrophy, cotton wool spots, flame hemorrhage, and dot and blot hemorrhage on fundoscopic examination of the eye may be present.
Laboratory Findings
Laboratory findings consistent with the diagnosis of glucagonoma include serum glucagon concentration of 1000pg/ml or greater.[6][7]
CT
Findings on abdominal CT scan suggestive of glucagonoma include reinforced mass in the arterial phase of the enhanced CT scan.[8]
MRI
Abdominal MRI is helpful in the diagnosis of glucagonoma. On abdominal MRI, glucagonoma is characterized by a mass which is hypointense on T1-weighted MRI and hyperintense on T2-weighted MRI.[8]
Ultrasonography
Abdominal ultrasound scan may be helpful in the diagnosis of glucagonoma. Findings on ultrasound scan suggestive of glucagonoma is hypoechoic tumor in the distal pancreas.[9]
Other Imaging Findings
Other imaging studies for glucagonoma include positron emission tomography scan and somatostation receptor scintigraphy.
Other Diagnostic Studies
Other diagnostic study for glucagonoma includes biopsy, which demonstrates epidermal necrosis, subcorneal pustules, either isolated or associated with necrosis of the epidermis, confluent parakeratosis, epidermal hyperplasia, and marked papillary dermal angioplasia and suppurative folliculitis.
Medical Therapy
The predominant therapy for glucagonoma is surgical resection. Adjunctive chemotherapy may be required.
Surgery
Surgery is the mainstay of treatment for glucagonoma. The feasibility of surgery depends on the stage of glucagonoma at diagnosis.[6]
Primary Prevention
There is no established method for prevention of glucagonoma.
Secondary Prevention
Secondary prevention measures of glucagonoma include routine glucagon levels and imaging at scheduled intervals after treatment.[10]
References
- ↑ 1.0 1.1 Glucagonoma. Wikipedia. https://en.wikipedia.org/wiki/Glucagonoma. Accessed on October 13, 2015.
- ↑ 2.0 2.1 2.2 2.3 Afsharfard A, Atqiaee K, Lotfollahzadeh S, Alborzi M, Derakhshanfar A (2012). "Necrolytic migratory erythema as the first manifestation of glucagonoma". Case Rep Surg. 2012: 974210. doi:10.1155/2012/974210. PMC 3434377. PMID 22970401.
- ↑ 3.0 3.1 Cardoso Filho Fde A, Feitosa RG, Fechine CO, Matos CM, Cardoso AL, Cardoso DL (2015). "Glucagonoma syndrome associated with necrolytic migratory erythema". Rev Assoc Med Bras. 61 (3): 203–6. doi:10.1590/1806-9282.61.03.203. PMID 26248239.
- ↑ 4.0 4.1 4.2 Glucagonoma. U.S. National Library of Medicine. https://www.nlm.nih.gov/medlineplus/ency/article/000326.htm
- ↑ 5.0 5.1 Stage Information for Pancreatic Neuroendocrine Tumors (Islet Cell Tumors). http://www.cancer.gov/types/pancreatic/hp/pnet-treatment-pdq#section/_199
- ↑ 6.0 6.1 6.2 6.3 Zhang M, Xu X, Shen Y, Hu ZH, Wu LM, Zheng SS (2004). "Clinical experience in diagnosis and treatment of glucagonoma syndrome". Hepatobiliary Pancreat Dis Int. 3 (3): 473–5. PMID 15313692.
- ↑ 7.0 7.1 Glucagonoma. Wikipedia. https://en.wikipedia.org/wiki/Glucagonoma. Accessed on October 15,2015
- ↑ 8.0 8.1 8.2 8.3 Lv WF, Han JK, Liu X, Wang SC, Pan BO, Xu AO (2015). "Imaging features of glucagonoma syndrome: A case report and review of the literature". Oncol Lett. 9 (4): 1579–1582. doi:10.3892/ol.2015.2930. PMC 4356379. PMID 25789004.
- ↑ 9.0 9.1 Koike N, Hatori T, Imaizumi T, Harada N, Fukuda A, Takasaki K; et al. (2003). "Malignant glucagonoma of the pancreas diagnoses through anemia and diabetes mellitus". J Hepatobiliary Pancreat Surg. 10 (1): 101–5. PMID 12918465.
- ↑ 10.0 10.1 Halvorson SA, Gilbert E, Hopkins RS, Liu H, Lopez C, Chu M; et al. (2013). "Putting the pieces together: necrolytic migratory erythema and the glucagonoma syndrome". J Gen Intern Med. 28 (11): 1525–9. doi:10.1007/s11606-013-2490-5. PMC 3797362. PMID 23681843.
- ↑ USPTF.http://http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=glucagonoma