Glucagonoma Guidelines

Updated: Dec 16, 2022
  • Author: Ricardo R Correa Marquez, MD, EsD, FACP, FACE, FAPCR, CMQ, ABDA, FACHT; Chief Editor: George T Griffing, MD  more...
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Guidelines

Guidelines Summary

The following organizations have issued guidelines for the diagnosis and management of glucagonoma:

  • National Comprehensive Cancer Network (NCCN) [43]
  • North American Neuroendocrine Tumor Society (NANETS) [36, 38]

Diagnosis

The NCCN guidelines recommend the following testing for the diagnosis of glucagonoma [43] :

  • Glucagon and blood glucose
  • Multiphasic computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen with or without the pelvis

The following testing may be appropriate [43] :

  • Somatostatin receptor (SSTR) positron emission tomography (PET)/CT or SSTR-PET/MRI
  • Chest CT with or without contrast
  • Endoscopic ultrasound
  • Biochemical evaluation when clinically indicated
  • Consider genetic testing and counseling for inherited genetic syndromes

Overall, the NANETS guidelines concur with the recommendations above. With regard to screening patients for inherited genetic syndromes, NANETS guidelines recommend that patients with glucagonoma undergo a thorough history (including family history) and physical examination (including skin examination) to identify symptoms and signs of multiple endocrine neoplasia type 1 (MEN1), von Hippel-Lindau (VHL) syndrome, neurofibromatosis type 1 (NF1), or tuberous sclerosis complex type 1 and 2 (TSC1-2). If any of those syndromes is suggested, the patient should be referred to a medical geneticist for further evaluation. [38]   

Testing for MEN1 is indicated in patients who have any other MEN1-associated tumors such as the following [38] :

  • Pa parathyroid adenoma or multigland hyperplasia
  • Thymic or bronchial neuroendocrine tumor
  • Pituitary adenoma
  • Adrenal nodule

Treatment

The NCCN's recommended treatment for symptoms and/or tumor control in locoregional disease includes octreotide long-acting release (LAR) 20–30 mg IM or lanreotide 120 mg SC every 4 weeks. For added symptom control, octreotide 100–250 mcg SC TID can be considered. Diabetes and hyperglycemia should be treated as appropriate. The recommended surgical intervention is distal pancreatectomy, peripancreatic lymphadenectomy, and splenectomy. [43]

NANETS also recommends the somatostatin analogues octreotide or lanreotide as first-line treatment of glucagonoma and glucagonoma syndrome. [38] Localized, biochemically confirmed glucagonoma should be resected for control of the tumor and management of glucagonoma syndrome. [36]

For metastatic disease, NCCN guidelines recommend resection of metastases and primary tumor, if complete resection is possible. [43] The NANETS guideline conference reached no consensus on the benefit of resection of primary tumors in patients with metastases. The guidelines do suggest that factors to be considered in individual cases include the following [36] :

  • Location of the tumor
  • Patient age and morbidities
  • Ability to treat or avoid local complications 
  • Possibility of improved response to peptide receptor radionuclide therapy (PRRT)

For progressive disease, the NCCN guidelines recommend managing clinically significant symptoms as appropriate. Octreotide LAR or lanreotide (if the patient is not already receiving it) should be considered. Alternative options for disease progression include the following [43] :

  • Clinical trial
  • Everolimus
  • Sunitinib
  • Temozolomide with capecitabine
  • PRRT with 177Lu-dotatate (if SSTR-positive and progression on octreotide LAR or lanreotide)
  • Other cytotoxic chemotherapy
  • Consider belzutifan in the setting of germline VHL alteration
  • Consider liver-directed therapy for liver-predominant disease
  • Palliative radiation therapy for symptomatic bone metastases