eMedicine Specialties > Endocrinology > Multiple Endocrine Disease and Miscellaneous Endocrine Disease
Glucagonoma: Treatment & Medication
Updated: Nov 20, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Currently, active drugs used to treat glucagonoma do not exist, although some drugs can cause partial regression of a neoplastic mass or improvements in the symptoms of necrolytic migratory erythema (NME).10
- In the literature, good results have been obtained with doxorubicin and streptozotocin (5-fluorouracil [5-FU] and streptozotocin), via selective damage of islets cells.9
- Long-acting octreotide, analogous to human somatostatin, causes NME symptom regression in some, but not all, patients.8,9,11,12
- The remission of glucagonoma through treatment with dacarbazine has been described in a single patient.
Surgical Care
Once a glucagonoma is identified, the optimal management is surgical resection, which is the only curative therapy.10,13,14
- In some patients, removal of the tumor may reverse symptoms.
- Patients with liver metastases and severe symptoms caused by tumor bulk or hormone-release syndromes may benefit from procedures that reduce hepatic arterial blood flow to metastases, including hepatic arterial occlusion with embolization or chemoembolization that causes a necrosis of the metastases without damaging the healthy hepatic parenchyma, which is supplied from the portal circulation.15,16 This treatment may also be combined with systemic chemotherapy in selected patients.
- Multimodal therapeutic interventions including liver transplantation are reported, but the results need further studies to confirm and validate such time and cost expensive procedure.17
- Beyond neoplasm removal, resect healthy surrounding parenchyma and locoregional lymph nodes, which can occasionally be metastatic or, more rarely, the primary site of the tumor.
- Several authors have reported the clinical palliation of symptoms from surgical debulking of the tumor.18
- Although first performed in 1996, laparoscopic resection of pancreatic endocrine tumors has seen only limited use, because there has not been a great deal of data about the safety, feasibility, indications for, and outcomes after such intervention. In 2008, however, Fernández-Cruz and colleagues reported on 49 patients who underwent laparoscopic pancreatic surgery.19 The authors concluded that such surgery is a safe, feasible means of treating benign endocrine pancreatic tumors.
Consultations
The occurrence of mucocutaneous lesions, endocrine disturbances, and optic and psychic disturbances may be very helpful for differential diagnosis, therapy, and needed consultations (from dermatologists, neurologists, endocrinologists, ophthalmologists).
Diet
In patients with glucagonoma, providing a supplemental protein supply in order to furnish amino acids is useful. In more severe cases, such supplementation can be administered intravenously. The administration of essential fatty acids (ie, olive oil), zinc, vitamins, and minerals is also helpful.
Activity
Mild exercise is usually not harmful in patients with glucagonoma.
Medication
Worldwide, octreotide is the only drug used for the treatment of glucagonomas.8,11,12 In patients with diffuse metastases, antiproliferative drugs may be useful for palliating symptoms.
Antisecretory agents
These medications include drugs with a multitude of endocrine and nonendocrine effects, including the inhibition of glucagon, VIP, and GI peptides.11
Octreotide (Sandostatin)
Synthetic analog of the hypothalamic peptide somatostatin that inhibits the secretion of pituitary and GI hormones, inducing an increase in the intestinal absorption of water and electrolytes, a decrease in pancreatic and gastric acid secretions, and a delay in intestinal transit time. Octreotide acts primarily on somatostatin receptor subtypes II and V. It inhibits GH secretion and has a multitude of other endocrine and nonendocrine effects, including the inhibition of glucagon, VIP, and GI peptides.
Adult
100 mcg SC tid/qid
Administer IV over 5 min in emergencies
Pediatric
Not established
May reduce effects of cyclosporine; patients on insulin, oral hypoglycemics, beta blockers, and calcium channel blockers may need dosage adjustments
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects are primarily related to altered GI motility and include nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; because of alteration in counterregulatory hormones (ie, insulin, glucagon, GH), hypoglycemia or hyperglycemia may be observed; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; because of inhibition of TSH secretion, hypothyroidism may also occur; exercise caution in patients with renal impairment; cholelithiasis may occur
Antineoplastic agents
These medications inhibit cell growth and differentiation.
Doxorubicin (Adriamycin, Rubex)
May be helpful for the palliation of symptoms in patients with progressive disease. The dosage is related to body surface area.
Adult
60-75 mg/m2 IV single dose q3-4wk, maximum cumulative dose 550 mg/m2 or 400 mg/m2 with previous or concomitant treatment (eg, daunorubicin, cyclophosphamide, irradiation of cardiac region)
Pediatric
Not established
May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels of doxorubicin; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity of doxorubicin; cyclophosphamide increases cardiac toxicity of doxorubicin
Documented hypersensitivity; severe CHF; cardiomyopathy; impaired cardiac function; preexisting myelosuppression; previous treatment with complete cumulative doses of doxorubicin, idarubicin, and/or daunorubicin
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause nausea and reddish stain of urine (not blood in urine) in the short term and toxicity of heart, oral mucosa, hair (alopecia), and hematopoietic system; extravasation may occur, resulting in severe tissue necrosis; caution in patients with impaired hepatic function
Fluorouracil (Adrucil)
Useful for the palliation of symptoms in patients with progressive disease.
Adult
15 mg/kg/d IV (continuous 24 h infusion) for 5 consecutive d
Pediatric
Not established
Allopurinol decreases toxicity; cimetidine increases plasma levels
Documented hypersensitivity; potentially serious infection; bone marrow depression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Nausea, oral and GI ulcers; may depress immune system and cause bone marrow suppression; caution in severe renal impairment, adjust dose
Streptozocin (Zanosar)
Helpful for the palliation of symptoms in patients with progressive disease. The dosage is related to body surface area. Streptozocin may sometimes cause complete disease remission. The drug's administration must be suspended only when the desired response or toxicity occurs. Streptozocin may induce severe nephrotoxic effects.
Adult
500 mg/m2 IV for 5 consecutive d q4-6wk
Pediatric
Not established
Loop diuretics, aminoglycosides, and amphotericin B may enhance nephrotoxicity
Documented hypersensitivity; severe renal impairment
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Streptozocin-induced nephrotoxicity may be irreversible and lead to death; may cause hypoglycemia and hyperglycemia; caution in diabetic patients
Dacarbazine (DTIC-Dome)
Administration in patients with glucagonoma not established; however, dacarbazine may be helpful for the palliation of symptoms in patients in whom surgery is not feasible. Complete disease remission has been reported in only 1 patient.
Adult
300 mg/m2 IV for 5 consecutive d q3-4wk
Pediatric
Not established
None reported
Documented hypersensitivity; severe chronic hepatic impairment
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May depress immune system and cause bone marrow suppression; caution in severe renal impairment, adjust dose
More on Glucagonoma |
| Overview: Glucagonoma |
| Differential Diagnoses & Workup: Glucagonoma |
 Treatment & Medication: Glucagonoma |
| Follow-up: Glucagonoma |
| Multimedia: Glucagonoma |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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Further Reading
Related eMedicine topics:
Glucagonoma Syndrome
Diabetes Mellitus, Type 2 [Endocrinology]
Diabetes Mellitus, Type 2 [Pediatrics: General Medicine]
Diabetes Mellitus, Type 2 - A Review
Multiple Endocrine Neoplasia
Multiple Endocrine Neoplasia Type 1
Multiple Endocrine Neoplasia, Type 2
Neoplasms of the Endocrine Pancreas
Pancreas, Islet Cell Tumors
Keywords
glucagonoma, glucagon, glucagonoma syndrome, alpha-cell tumor, alpha-cell adenoma, alpha cell, alpha cells, alpha-2 cell, alpha-2 cells, diabetes, diabetes mellitus, diabetes mellitus type 2, pancreas, hyperglycemia, hyperglycemic, neuroendocrine, 4D syndrome, neuroendocrine tumor, islet cell, islet cells, islet cell pancreatic tumor, pancreatic tumor, pancreas tumor, insulin, insulinoma, glucagon overproduction, hypoaminoacidemia, weight loss, normochromic and normocytic anemia, necrolytic migratory erythema, NME, hyperglucagonemia, pancreas, octreotide, Sandostatin, peptide hormone, bioactive peptide, tumor of the pancreas, multiple endocrine neoplasia type1, MEN I, islet celltumor
