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Hypoglycemia Workup

  • Author: Osama Hamdy, MD, PhD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
 
Updated: Jul 05, 2016
 

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. 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.[15]

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 oft Diagnostic algorithm. A systematic approach is often required to establish the true cause of hypoglycemia, using an algorithmic approach.
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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. Also measure the beta-hydroxybutyrate serum level. Glucose and/or glucagon must be administered after blood sample withdrawal to abort hypoglycemic symptoms. The diagnosis of insulinoma is likely if the patient, at the conclusion of the fast, has neuroglycopenic symptoms, a fall in plasma glucose to less than 45 mg/dL (< 2.5 mmol/L), inappropriately elevated beta-cell polypeptides (insulin, proinsulin, and C-peptide levels), and a beta-hydroxybutyrate level of less than 2.7 mmol/L.

For overnight fasting plasma glucose levels, symptoms of hypoglycemia may develop when the blood sugar is below 60 mg/dL (3.33 mmol/L).

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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.[11]

C-peptide levels are elevated in insulinoma, normal or low with exogenous insulin, and elevated with oral sulfonylureas.

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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.

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Contributor Information and Disclosures
Author

Osama Hamdy, MD, PhD Medical Director, Obesity Clinical Program, Director of Inpatient Diabetes Program, Joslin Diabetes Center; Assistant Professor of Medicine, Harvard Medical School

Osama Hamdy, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association

Disclosure: Received consulting fee from Merck Inc for speaking and teaching; Received consulting fee from Abbott Nutrition for consulting; Received grant/research funds from Metagenics for research support; Received grant/research funds from Neurometrix for research support.

Coauthor(s)

Kenneth J Snow, MD Associate Chief, Adult Diabetes, Joslin Clinic

Kenneth J Snow, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Vellore A R Srinivasan, MSc, PhD Professor of Biochemistry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth University, India

Disclosure: Received salary from Sri Balaji Vidyapeeth University, Mahatma Gandhi Medical College and Research Institute campus , Pondicherry ( Puducherry ) , India . P.C. 607 402 for employment.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Vasudevan A Raghavan, MBBS, MD, MRCP(UK) Director, Cardiometabolic and Lipid (CAMEL) Clinic Services, Division of Endocrinology, Scott and White Hospital, Texas A&M Health Science Center College of Medicine

Vasudevan A Raghavan, MBBS, MD, MRCP(UK) is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Heart Association, Endocrine Society, National Lipid Association, and Royal College of Physicians

Disclosure: Nothing to disclose.

David S Schade, MD Chief, Division of Endocrinology and Metabolism, Professor, Department of Internal Medicine, University of New Mexico School of Medicine and Health Sciences Center

David S Schade, MD is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Federation for Medical Research, Endocrine Society, New Mexico Medical Society, New York Academy of Sciences, and Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Diagnostic algorithm. A systematic approach is often required to establish the true cause of hypoglycemia, using an algorithmic approach.
 
 
 
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