Approach Considerations
Search for a source of infection. Studies should be considered to rule out the possibility of a concurrent occult infection contributing to the new hypoglycemic episode (eg, complete physical examination, chest radiography (particularly in diabetic patients presenting with hypoglycemia), urinalysis, blood cultures).
Check liver function tests, serum insulin levels, and cortisol and thyroid levels. Insulin radioimmunoassay may be warranted if an islet cell tumor is suspected (elevated insulin levels).
Proinsulin normally represents less than 20% of total immunoreactive insulin. In patients with islet-cell tumors, proinsulin may contribute as much as 70% of insulin immunoreactivity.
Provocative tests involving the administration of arginine, leucine, calcium, glucagon, or tolbutamide are generally of limited value, because their sensitivity or specificity is inadequate.[11]
Other causes of hypoglycemia should be properly investigated (see Differentials). For example, a morning cortisol level determination and/or adrenocorticotropic hormone (ACTH) stimulation testing should be performed if adrenal insufficiency is suspected.
See a diagnostic algorithm for hypoglycemia below.
Diagnostic algorithm. A systematic approach is often required to establish the true cause of hypoglycemia, using an algorithmic approach. Glucose and Insulin Levels
During hypoglycemic episodes, patients should test their glucose at home to document hypoglycemia that is occurring with the episodes. Take into consideration that meter readings may not be accurate enough to establish the diagnosis.
Test glucose and insulin levels simultaneously to document low glucose levels occurring in conjunction with inappropriate insulin levels.
Keep in mind that whole blood glucose values may be spuriously low in polycythemia rubra vera because of the unequal distribution of glucose between erythrocytes and plasma, excessive glycolysis by erythrocytes, or both. Low blood glucose values in leukemia are due to excessive glycolysis by leukocytes and in hemolytic crisis from excessive glycolysis by nucleated erythrocytes. In the polycythemic patient or in serum of the leukemic or hemolytic patient, prompt measurement of glucose in plasma to which an antiglycolytic agent has been added should provide accurate results.
Oral glucose tolerance test
Administer an oral glucose tolerance test if reactive hypoglycemia is suspected. An oral glucose tolerance test provides little benefit for the evaluation of fasting hypoglycemia. Perform the test for 5 hours while simultaneously testing glucose and insulin levels. To be meaningful, low blood sugar (< 50 mg/dL [< 2.78 mmol/L]) during the test should be accompanied by typical symptoms. Response to a mixed meal may be more representative.
72-hour fasting plasma glucose
A supervised fast is the most reliable diagnostic test for the evaluation of fasting hypoglycemia. Continue the fast for as long as 72 hours or until symptoms develop in the presence of hypoglycemia (blood sugar < 45 mg/dL (2.5 mmol/L) for women; < 55 mg/dL (3.05 mmol/L) for men). Obtain simultaneous insulin levels every 6 hours, when glucose is low and when symptoms develop. Glucose and/or glucagon must be administered after blood sample withdrawal to abort hypoglycemic symptoms.
For overnight fasting plasma glucose levels, symptoms of hypoglycemia may develop when the blood sugar is below 60 mg/dL (3.33 mmol/L).
C-Peptide Levels
Obtain C-peptide levels any time an elevated insulin level is obtained. Endogenous hyperinsulinemia from insulinoma is associated with elevated C-peptide concentrations with concurrent hypoglycemia. Exogenous hyperinsulinemia from injected insulin results in low concentrations of C-peptide, both because of the effect of the associated hypoglycemia and because of the direct suppressive effect of insulin on the pancreatic beta cell.[6]
C-peptide levels are elevated in insulinoma, normal or low with exogenous insulin, and elevated with oral sulfonylureas.
Radiologic Studies
For the evaluation of insulinomas, computed tomography (CT) scanning and ultrasonography often are not helpful, because most of these tumors are small. Magnetic resonance imaging (MRI) may yield better results.
Selective percutaneous transhepatic venous sampling often is helpful for localizing an insulinoma to the head, body, or tail of the pancreas, and selective arteriography is also often helpful in localizing insulin-secreting lesions. Octreotide scanning localizes insulinomas in approximately 50% of cases.
Retroperitoneal tumors that are producing insulinlike growth factor (IGF) are usually imaged easily using a CT scan.
Hill NR, Thompson B, Bruce J, et al. Glycaemic risk assessment in children and young people with Type 1 diabetes mellitus. Diabet Med. Jul 2009;26(7):740-3. [Medline].
Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. Aug 5 2009;[Medline].
Prolonged Nocturnal Hypoglycemia Is Common During 12 Months Of Continuous Glucose Monitoring In Children And Adults With Type 1 Diabetes. Diabetes Care. Mar 3 2010;[Medline].
Swinnen SG, Dain MP, Aronson R, et al. A 24-week, randomized, treat-to-target trial comparing initiation of insulin glargine once-daily with insulin detemir twice-daily in patients with type 2 diabetes inadequately controlled on oral glucose-lowering drugs. Diabetes Care. Mar 3 2010;[Medline].
Ito T, Otsuki M, Igarashi H, et al. Epidemiological Study of Pancreatic Diabetes in Japan in 2005: A Nationwide Study. Pancreas. Feb 22 2010;[Medline].
Chen L. A literature review of intensive insulin therapy and mortality in critically ill patients. Clin Nurse Spec. Mar-Apr 2010;24(2):80-6. [Medline].
Garza H. Minimizing the risk of hypoglycemia in older adults: a focus on long-term care. Consult Pharm. Jun 2009;24 Suppl B:18-24. [Medline].
Boucai L, Southern WN, Zonszein J. Hypoglycemia-associated Mortality Is Not Drug-associated but Linked to Comorbidities. Am J Med. Nov 2011;124(11):1028-35. [Medline]. [Full Text].
Feil DG, Rajan M, Soroka O, et al. Risk of hypoglycemia in older veterans with dementia and cognitive impairment: implications for practice and policy. J Am Geriatr Soc. Dec 2011;59(12):2263-72. [Medline].
Pugh SK, Doherty DA, Magann EF, et al. Does hypoglycemia following a glucose challenge test identify a high risk pregnancy?. Reprod Health. Jul 14 2009;6:10. [Medline].
Lin YY, Hsu CW, Sheu WH, Chu SJ, Wu CP, Tsai SH. Use of therapeutic responses to glucose replacement to predict glucose patterns in diabetic patients presenting with severe hypoglycaemia. Int J Clin Pract. Aug 2009;63(8):1161-6. [Medline].
Egi M, Bellomo R, Stachowski E, et al. Hypoglycemia and outcome in critically ill patients. Mayo Clin Proc. Mar 2010;85(3):217-24. [Medline].
Goh HK, Chew DE, Miranda IG, Tan L, Lim GH. 24-Hour observational ward management of diabetic patients presenting with hypoglycaemia: a prospective observational study. Emerg Med J. Oct 2009;26(10):719-23. [Medline].
Sinert R, Su M, Secko M, Zehtabchi S. The utility of routine laboratory testing in hypoglycaemic emergency department patients. Emerg Med J. Jan 2009;26(1):28-31. [Medline].
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