eMedicine Specialties > Endocrinology > Diabetes Mellitus

Hypoglycemia: Differential Diagnoses & Workup

Author: Vasudevan A Raghavan, MBBS, MD, MRCP, Assistant Professor, Department of Internal Medicine, Divisions of Endocrinology, Diabetes and Metabolism and Cardiovascular Sciences, Ohio State University; Co-director of The Ross Heart Hospital Comprehensive Lipid Management Clinic, Ohio State University Medical Center
Coauthor(s): Vellore A R Srinivasan, MSc, PhD, Associate Professor, Department of Biochemistry, Sri Balaji Vidyapeeth University, Mahatma Gandhi Medical College and Research Institute campus, Puducherry, India; Kenneth J Snow, MD, Associate Chief, Adult Diabetes, Joslin Clinic
Contributor Information and Disclosures

Updated: Aug 18, 2009

Overview
Differential Diagnoses & Workup
Treatment & Medication
Follow-up
Multimedia

Differential Diagnoses

Addison Disease	Hypopituitarism (Panhypopituitarism)
Adrenal Crisis	Insulin Resistance
Alcoholism	Insulinoma
Anxiety Disorders	Pseudohypoglycemia
Cardiogenic Shock

Workup

Laboratory Studies

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.
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 during the test should be accompanied by typical symptoms. Response to a mixed meal may be more representative.
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 for women, <55 mg/dL 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.
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.
Other causes of hypoglycemia should be properly investigated. For example, a morning cortisol level determination and/or adrenocorticotropic hormone (ACTH) stimulation testing should be performed if adrenal insufficiency is suspected.
Remember 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.

Imaging Studies

For the evaluation of insulinomas, CT scan and ultrasound often are not helpful because most of these tumors are small. MRI may be better.
Selective arteriography often is helpful.
Selective percutaneous transhepatic venous sampling often is helpful for localizing an insulinoma to the head, body, or tail of the pancreas.
Octreotide scanning localizes insulinomas in approximately half the cases.
Intraoperative ultrasound can be used as a diagnostic aid.
Retroperitoneal tumors that are producing insulin-like growth factor (IGF) usually are imaged easily using a CT scan.

Other Tests

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 generally are of limited value because their sensitivity or specificity is inadequate.⁵
Diagnostic algorithm: A systematic approach is often required to establish the true cause of hypoglycemia, using an algorithmic approach. One such algorithm is given below (see image below and Image 1).

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

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

More on Hypoglycemia

Overview: Hypoglycemia

Differential Diagnoses & Workup: Hypoglycemia

Treatment & Medication: Hypoglycemia

Follow-up: Hypoglycemia

Multimedia: Hypoglycemia

References

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].
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].
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].
Cryer PE, Polonsky KS. Glucose homeostasis and hypoglycemia. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR, eds. Williams Textbook of Endocrinology. 9^th ed. Philadelphia, Pa: WB Saunders; 1998:939-71.
Field JB. Hypoglycemia. Definition, clinical presentations, classification, and laboratory tests. Endocrinol Metab Clin North Am. Mar 1989;18(1):27-43. [Medline].
Ibarra JD Jr. Hypoglycemia. Postgrad Med. Feb 1972;51(2):88-93. [Medline].
Koch B. Selected topics of hypoglycemia care. Can Fam Physician. Apr 2006;52:466-71. [Medline].
Service FJ. Classification of hypoglycemic disorders. Endocrinol Metab Clin North Am. Sep 1999;28(3):501-17, vi. [Medline].
Service FJ. Diagnostic approach to adults with hypoglycemic disorders. Endocrinol Metab Clin North Am. Sep 1999;28(3):519-32, vi. [Medline].
Service FJ. Hypoglycemia. Endocrinol Metab Clin North Am. Dec 1997;26(4):937-55. [Medline].
Service FJ. Hypoglycemic disorders. N Engl J Med. Apr 27 1995;332(17):1144-52. [Medline].
Shamoon H. Hypoglycemia. In: Endocrinology and Metabolism. 3^rd ed. New York, NY: McGraw-Hill; 1995:1251-69.

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Keywords

hypoglycemia, blood sugar, blood glucose, low blood sugar, high blood sugar, type 2 diabetes, diabetes mellitus, plasma glucose disorder, glucose disorder, low blood sugar, Whipple triad, decreased glucose, insulin-producing tumor, neuroglycopenic symptoms, reactive hypoglycemia, fasting hypoglycemia, hypoglycemic disorder, hypoglycemic

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Contributor Information and Disclosures

Author

Vasudevan A Raghavan, MBBS, MD, MRCP, Assistant Professor, Department of Internal Medicine, Divisions of Endocrinology, Diabetes and Metabolism and Cardiovascular Sciences, Ohio State University; Co-director of The Ross Heart Hospital Comprehensive Lipid Management Clinic, Ohio State University Medical Center
Vasudevan A Raghavan, MBBS, MD, MRCP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, Endocrine Society, National Lipid Association, and Royal College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Vellore A R Srinivasan, MSc, PhD, Associate Professor, Department of Biochemistry, Sri Balaji Vidyapeeth University, Mahatma Gandhi Medical College and Research Institute campus, Puducherry, India
Disclosure: Sri Balaji Vidyapeeth University, Mahatma Gandhi Medical College and Research Institute campus , Pondicherry ( Puducherry ) , India . P.C. 607 402 Salary Employment

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, and Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Yoram Shenker, MD, Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison
Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

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eMedicine Specialties > Endocrinology > Diabetes Mellitus

Hypoglycemia: Differential Diagnoses & Workup

Differential Diagnoses

Other Problems to Be Considered

Workup

Laboratory Studies

Imaging Studies

Other Tests

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

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

More on Hypoglycemia

References

Further Reading

Keywords

Contributor Information and Disclosures

Author

Coauthor(s)

Medical Editor

Pharmacy Editor

Managing Editor

CME Editor

Chief Editor