Diagnosis and follow-up of glucagonomas and other glucagon-producing tumors
Assessing diabetic patients with problematic hyper- or hypoglycemic
Immunoassay
Plasma EDTA
Patient Preparation: Fasting (8 hours)
Supplies: Sarstedt 5 mL Aliquot Tube (T914)
Collection Container/Tube: Lavender top (EDTA)
Submission Container/Tube: Plastic vial
Specimen Volume: 2 mL
Collection Instructions:
1. Pre-chill tube at 4 degrees C before drawing the specimen.
2. Draw into the pre-chilled tube, and process as follows:
a. After drawing specimen, chill tube in wet ice for 10 minutes.
b. Centrifuge in a refrigerated centrifuge or in chilled centrifuge carrier.
c. Immediately after centrifugation, aliquot plasma into a plastic vial, and freeze.
If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen
0.45 mL
Gross hemolysis | Reject |
Gross lipemia | OK |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Plasma EDTA | Frozen (preferred) | 90 days |
Diagnosis and follow-up of glucagonomas and other glucagon-producing tumors
Assessing diabetic patients with problematic hyper- or hypoglycemic
Glucagon is a single-chain polypeptide of 29 amino acids that is derived from a larger precursor peptide (big plasma glucagon) that is cleaved upon secretion. The main sites of glucagon production are the hypothalamus and pancreatic alpha-islet cells. The function of hypothalamic glucagon is incompletely understood and currently no clinical disorders of hypothalamic glucagon function have been defined. Pancreatic islet glucagon is secreted in response to hypoglycemia, with resultant increases in blood glucose concentration. Glucagon's hyperglycemic effect is produced by stimulating hepatic glycogenolysis and gluconeogenesis; it has no effect on muscle glycogen. Once blood glucose levels have normalized, glucagon secretion ceases.
Excessive glucagon secretion can lead to hyperglycemia. Excessive and inappropriate glucagon secretion can sometimes be observed in diabetes, in particular during ketoacidosis, and can complicate management of the disorder. In rare cases, it also can occur in tumors of the pancreatic islets (glucagonoma), carcinoid tumors and other neuroendocrine neoplasms, and hepatocellular carcinomas. Patients with glucagon-secreting tumors may present with classic glucagonoma syndrome, consisting of necrolytic migratory erythema, diabetes, and diarrhea but can also have more subtle symptoms and signs.
Decreased or absent glucagon response to hypoglycemia can be seen in type I diabetes (insulin-dependent diabetes) and can contribute to severe and prolonged hypoglycemic responses.
Glucagon is routinely measured along with serum glucose, insulin, and C-peptide levels, during the mixed-meal test employed in the diagnostic workup of suspected postprandial hypoglycemia. However, it plays only a minor role in the interpretation of this test.
< or =6 hours: 100-650 pg/mL
1-2 days: 70-450 pg/mL
2-4 days: 100-650 pg/mL
4-14 days: declining gradually to adult levels
>14 days: < or =80 pg/mL (range based on 95% confidence limits)
Glucagon levels are inversely related to blood glucose levels at all ages. This is particularly pronounced at birth and shortly thereafter, until regular feeding patterns are established. This explains the higher levels immediately after birth, which then first fall as the glucagon release mobilizes the
For SI unit Reference Values, see https://www.mayocliniclabs.com/order-tests/si-unit-conversion.html
Elevated glucagon levels in the absence of hypoglycemia may
Inappropriate elevations in glucagon levels in hyperglycemic
In diabetic patients, low glucagon levels (undetectable or in the
Results obtained with different glucagon assays can differ substantially. This can be caused by use of different calibration standards. Different glucagon assays may also exhibit variable cross-reactivity with different isoforms of glucagon, not all of which are biologically active. Some assays, including this one, remove biologically inactive isoforms before measurement, while others do not. All these factors contribute to the differences between different assays. Therefore, serial measurements should always be performed using the same assay.
The heterogeneity of plasma glucagon is well established. It has at least 3 major components. In addition to the biologically active glucagon (MW 3500) and its possible precursor (MW 9000), there also is big plasma glucagon (BGP) of unknown biological significance. By using ethanol extraction, BPG (considered to be an interfering factor in the glucagon assay) is removed. Therefore, the assay measures only biologically active glucagon and its precursors.
Precise reference ranges for appropriate glucagon responses for given blood glucose ranges are not well established and vary widely from assay to assay. Expert advice should be sought when interpreting inappropriately low glucagon levels or when interpreting glucagon, insulin, and C-peptide levels obtained during mixed-meal testing.
Diabetics, obese subjects, acromegalics, and patients with Cushing syndrome have higher glucagon levels.
Tumor marker tests, including glucagon, are not specific for malignancy. All immunometric assays can, on rare occasions, be subject to hooking at extremely high analyte concentrations (false-low results), heterophilic antibody interference (false-high results), or autoantibody interference (unpredictable effects). If the laboratory result does not fit the clinical picture, these possibilities should be considered.
1. Tomassetti P, Migliori M, Lalli S, et al: Epidemiology, clinical features and diagnosis of gastroenteropancreatic endocrine tumours. Ann Oncol. 2001;12 Suppl 2:S95-99
2. Jhiang G, Zhang BB: Glucagon and regulation of glucose metabolism. Am J Physiol Metab. 2003;284:E671-E678
3. vanBeek AP, de Haas ER, van Vloten WA, et al: The glucagonoma syndrome and necrolytic migratory erythema: a clinical review. Eu J Endocrinol. 2004;151:531-537
4. Cruz-Bautista I, Lerman I, Perez-Enriquez B, et al: Diagnostic challenge of glucagonoma: case report and literature review. Endocr Pract. 2006 Jul-Aug;12(4):422-426
5. Falconi M, Eriksson B, Kaltsas G, et al: ENETS Consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology. 2016;103(2):2153-2171
Big plasma glucagon (BPG), which is considered to be biologically inactive, is extracted using ethanol prior to assay of the specimen. Following ethanol extraction, glucagon reacts with an anti-glucagon antibody that is attached to magnetic beads. After incubation and washing, a second detection antibody is added and attaches to any bead-bound glucagon, forming a sandwich assay. A streptavidin-phycoerythrin (SPE) tag binds to the glucagon-antibody complex. Laser-based fluorescent analysis of the resulting glucagon-antibody-SPE complex is performed on the Luminex 200 instrument.(Package insert: Human Glucagon Magnetic Bead Kit, Millipore Sigma; Rev. 12/26/2018)
Monday, Wednesday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
82943
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
GLP | Glucagon, P | 2338-2 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
9358 | Glucagon, P | 2338-2 |