AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Hypoglycemia is considered present when serum glucose level is less than 50 mg/dL. However, more specifically, it is defined as a decrease in the blood glucose level or its tissue utilization that results in demonstrable signs or symptoms. These signs or symptoms usually include altered mental status and/or sympathetic nervous system stimulation. The glucose level at which an individual becomes symptomatic is highly variable.

Pathophysiology

The organ systems that manifest the signs and symptoms of hypoglycemia are the central and autonomic nervous systems.

Hypoglycemia can be due to alimentary problems, idiopathic causes, fasting, insulinoma, endocrine problems, extrapancreatic causes, hepatic disease, and miscellaneous causes.

Mortality/Morbidity

Delay in treatment can result in profound sequelae, including death.

• Acute sequelae include coma, cardiac dysrhythmia, and death.
• The risk of permanent neurologic deficits increases with prolonged hypoglycemia; such deficits can include hemiparesis, memory impairment, diminished language skills, decreased abstract thinking capabilities, and ataxia.
• Because the consequences of hypoglycemia can be devastating and an antidote is readily available, diagnosis and treatment must be rapid in any patient with suspected hypoglycemia, regardless of the cause.

Sex

Females are affected by hypoglycemia more than males.

Age

Hypoglycemia affects predominantly older adults.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients often have a history of diabetes mellitus.
• A history of insulin usage or ingestion of an oral hypoglycemic agent may be known, and possible toxic ingestion should be considered.
• Inquire if the patient is taking any new medications.
• Obtaining an accurate medical history may be difficult if the patient's mental status is altered.
• The medical history may include diabetes mellitus, renal insufficiency/failure, alcoholism, hepatic cirrhosis/failure, other endocrine diseases, or recent surgery.
• The patient's medication and drug history should be reviewed carefully for potential causes of hypoglycemia.
• The social history may include ethanol intake and nutritional deficiency.
• Review systems for weight reduction, fatigue, somnolence, nausea and vomiting, and headache.
• Look for other symptoms suggesting infection.
• Central nervous system
• • Headache
  • Confusion
  • Personality changes
• Cardiovascular system - Palpitations
• GI symptoms
• • Hunger
  • Nausea
  • Belching
• Adrenergic symptoms
• • Sweating
  • Anxiety
  • Tremulousness
  • Nervousness

Physical

Physical findings are nonspecific in hypoglycemia and generally are related to the central and autonomic nervous systems.

• Assess vital signs for hypothermia, tachypnea, tachycardia, hypertension, and bradycardia (neonates).
• The head, eyes, ears, nose, and throat (HEENT) examination may indicate blurred vision, pupils normal to fixed and dilated, icterus (usually cholestatic due to hepatic disease), and parotid pain (due to endocrine causes).
• Cardiovascular disturbances may include tachycardia (bradycardia in neonates), hypertension or hypotension, and dysrhythmias.
• Respiratory disturbances may include dyspnea, tachypnea, and acute pulmonary edema.
• GI disturbances may include nausea and vomiting, dyspepsia, and abdominal cramping.
• Skin may be diaphoretic and warm or show signs of dehydration with decrease in turgor.
• Neurologic conditions include coma, confusion, fatigue, loss of coordination, combative or agitated disposition, stroke syndrome, tremors, convulsions, and diplopia.

Causes

• Causes of hypoglycemia are varied, but it is seen most often in diabetic patients.
• Hypoglycemia may result from medication changes or overdoses, infection, diet changes, metabolic changes over time, or activity changes; however, no acute cause may be found.
• Careful consideration should be given to all diabetic patients presenting with hypoglycemia. New medications, activity changes, and infection should be considered.
• Early in the course of non–insulin-dependent diabetes, patients may experience episodes of hypoglycemia several hours after meals. The symptoms generally are brief and respond spontaneously.
• Patients with no prior history of hypoglycemia require a complete workup to find a potentially treatable disease.
• Drugs that may be related to hypoglycemia include the following: oral hypoglycemics, sulfonamide, phenylbutazone, insulin, bishydroxy coumarin, salicylates, p-aminobenzoic acid, propoxyphene, haloperidol, stanozolol, ethanol, hypoglycin, carbamate insecticide, disopyramide, isoniazid, methanol, methotrexate, pentamidine, sulfonamide, tricyclic antidepressants, cytotoxic agents, organophosphates, propranolol plus ethanol, didanosine, chlorpromazine, quinine, sulfa drugs, fluoxetine, sertraline, fenfluramine, trimethoprim, 6-mercaptopurine, thiazide diuretics, thioglycolate, tremetol, ritodrine, disodium ethylenediaminetetraacetic acid (EDTA), clofibrate, angiotensin converting enzyme (ACE) inhibitors, and lithium.
• Factitious hypoglycemia or self-induced hypoglycemia can be seen in health care workers or in relatives who care for diabetic family members at home. Further discussion, including the diagnostic use of C-peptide levels and hemoglobin A1C, can be found in the articles Diabetes Mellitus, Type 1 - A Review and Diabetes Mellitus, Type 2 - A Review.
• Other causes include the following:
• • GI surgery
  • Idiopathic
  • Hepatic disease
  • Islet cell tumor/extrapancreatic tumor
  • Exercise (in diabetic patients)
  • Pregnancy
  • Renal glycosuria
  • Ketotic hypoglycemia of childhood
  • Adrenal insufficiency
  • Hypopituitarism
  • Enzyme deficiency
  • Large tumors (eg, mesenchymal tumors, epithelial tumors, endothelial tumors)
  • Sepsis
  • Starvation
  • Artifact

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Hypoglycemic agents (eg, insulin, oral hypoglycemic agents)
Drugs/toxins (eg, ethanol, salicylates, beta-blockers, pentamidine)
Endocrine disorders (eg, Addison disease, glucagon deficiency, carcinomas, extrahepatic tumors)
Hepatic disease (eg, cirrhosis, galactose intolerance, fructose intolerance, glycogen storage diseases)
Nutritional disorders (eg, prolonged starvation prior to anesthesia, protein calorie malnutrition, L-leucine-sensitive hypoglycemic defect in children, low-calorie ketogenic diet, renal disease)
Autoimmune disorders (eg, Graves disease)
Other (eg, Jamaican vomiting sickness, ingestion of ethanol-containing mouthwash or cologne [children], gastric surgery, potassium administration during periodic attacks of paralysis, excessive muscular activity, diarrhea [childhood])
CNS disorders
Psychogenic

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Treatment and disposition of hypoglycemia are guided by the history and the clinical picture. Serum glucose should be measured frequently and used to guide treatment, because clinical appearance alone may not reflect the seriousness of the situation.
• Hypoglycemia is defined according to the following serum glucose levels:
• • <50 mg/dL in men
  • <45 mg/dL in women
  • <40 mg/dL in infants and children
• If the cause of hypoglycemia is other than oral hypoglycemic agents or insulin in a diabetic patient, other lab tests may be necessary.
• • C-peptide measurement: This measurement is elevated in insulinoma, normal or low with exogenous insulin, and elevated with oral sulfonylureas.
  • Check liver function tests, serum insulin, and cortisol and thyroid levels.
• 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.
• • Complete physical examination
  • Chest radiograph
  • Urinalysis
  • Blood cultures

Imaging Studies

• Performing an abdominal CT scan or an ultrasound to rule out an abdominal tumor may be appropriate in the patient with new-onset hypoglycemia and no clear etiology.
• In diabetic patients presenting with hypoglycemia, perform a chest radiograph to rule out infection.

Other Tests

• Plasma glucose overnight fasting - <60 mg/dL (3.33 mmol/L)
• Plasma glucose 72-hour fasting
• • <45 mg/dL (2.5 mmol/L) for females
  • <55 mg/dL (3.05 mmol/L for males
• Oral glucose tolerance - <50 mg/dL (<2.78 mmol/L)
• Insulin radioimmunoassay - Insulin levels elevated if islet cell tumor present

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

Treatment of hypoglycemia consists of correcting the glucose deficiency and directing further treatment to the underlying cause.

• EMS care generally consists of drawing serum glucose or Accucheck prior to administering D50 in the field. This procedure usually is performed in the case of an unconscious patient or a patient with altered mental status.
• Many advanced cardiac life support (ACLS)-trained and first responders are able to perform simple bedside glucose testing. This procedure should be part of the normal protocol for any EMS unit.
• When hypoglycemia is found and treated in the diabetic patient, the patient may awaken and not desire transport.
• Considering the multiple causes of a sudden episode of hypoglycemia in a patient with previously well-controlled diabetes, advising transport and ED evaluation is prudent.

See Medscape's Diabetes & Endocrinology Resource Center for more information.

Emergency Department Care

• The initial approach should include the following: ABCs, intravenous (IV) access, oxygen, monitoring, and Accucheck. Administration of glucose as part of the initial evaluation of altered mental status often corrects hypoglycemia.
• As was the case in the field, treatment should not be withheld while waiting for a laboratory glucose value. Because the brain uses glucose as its primary energy source, neuronal damage may occur if treatment of hypoglycemia is delayed.
• • A hyperglycemic patient with an altered mental status may receive a bolus of glucose. This procedure is unlikely to harm the patient with high glucose; however, the delay in giving glucose to the hypoglycemic patient may be detrimental.
  • If an Accucheck can be performed immediately, awaiting the results of this test (available within 1 minute) before deciding whether to administer glucose is reasonable.
• Once the diagnosis of hypoglycemia is made, search carefully for the cause in the previously healthy patient.
• In the diabetic patient, search diligently for the cause (eg, medication changes, dietary changes, new metabolic changes, recent illness, occult infection) of the episode.

Consultations

• Consultation is guided generally by determination of the underlying cause of hypoglycemia.
• Endocrinology, toxicology, or infectious disease subspecialists may be consulted, but, in general, an internal medicine or family practice specialist can manage hypoglycemia and determine its underlying etiology.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The mainstay of therapy for hypoglycemia is glucose. Other medications may be administered based on the underlying cause or the accompanying symptoms; however, these medications are not addressed in this article.

Drug Category: Glucose supplement

This agent is used to raise the patient's serum glucose.

Drug Category: Glucose-elevating agents

These agents can act in the pancreas or the peripheral tissues to increase blood glucose levels.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients with no known cause or no previous episodes of hypoglycemia must be admitted for further evaluation.
• • For overdose, accidental ingestion, or therapeutic misadventures with oral hypoglycemics, little correlation exists between the amount of oral hypoglycemic agent ingested and the length or depth of coma. These patients require admission.
  • Inadequate data are available to predict the extent or the time course of hypoglycemia in children.
• Chlorpropamide has demonstrated refractory hypoglycemia for up to 6 days after ingestion. Asymptomatic patients who have ingested hypoglycemic agents should be observed for the development of hypoglycemia, because the onset of action and the half-life are extremely variable. The length of observation is based on the ingested agent.
• Admission criteria
• • No obvious cause
  • Oral hypoglycemic agent
  • Long-acting insulin
  • Persistent neurologic deficits
• Discharge may be considered after a high carbohydrate meal in the following situations:
• • Obvious cause is found and treated.
  • Episode is reversed rapidly.

Further Outpatient Care

• For patients on either short-acting insulin or hypoglycemic agents who have not eaten and have had their hypoglycemia reversed rapidly, a high carbohydrate meal prior to discharge is recommended.
• A competent adult who has been directed to monitor fingerstick glucose measurements closely during the remainder of the day should accompany the patient after discharge.

Deterrence/Prevention

• Patients must be counseled as to the causes and the early signs and symptoms of hypoglycemia. This counseling is particularly important for those patients who have a history of prior episodes of hypoglycemia or who are newly diagnosed diabetics.
• General outpatient diabetic education or inpatient diabetic teaching is indicated.

Complications

• Prolonged hypoglycemia may cause permanent neurologic deficit or death.
• Unrecognized infection causing hypoglycemia in diabetic patients may result in recurrent hypoglycemic spells or progression of the infection.

Prognosis

• The prognosis for this condition is excellent if detected and treated early.

Patient Education

• Diabetic patients with episodes of hypoglycemia need education in nutrition, checking glucose levels at home, and early signs and symptoms of hypoglycemia.
• Recognition of early symptoms is paramount for self-treatment.
• For excellent patient education resources, see eMedicine's Diabetes Center. Also, visit eMedicine's patient education article, Low Blood Sugar.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Discharging a patient following a hypoglycemic episode that is likely the result of a long-acting oral hypoglycemic medication is a potential pitfall. Any patient for whom the cause is not identified readily may have a recurrence of hypoglycemia with resultant sequelae.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Altuntas Y, Bilir M, Ucak S, Gundogdu S. Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function. Eur J Obstet Gynecol Reprod Biol. Apr 1 2005;119(2):198-205. [Medline].
• Bourcigaux N, Arnault-Ouary G, Christol R, et al. Treatment of hypoglycemia using combined glucocorticoid and recombinant human growth hormone in a patient with a metastatic non-islet cell tumor hypoglycemia. Clin Ther. Feb 2005;27(2):246-51. [Medline].
• Ellenhorn MJ, Barceloux DG. Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 1988:440-61.
• Goldfrank LR. Goldfrank's Toxicologic Emergencies. 1994:577-88.
• Haddad LM, Winchester JF. Clinical Management of Poisoning and Drug Overdose. 2^nd ed. 1990:1475-6.
• Hoffman RS, Goldfrank LR. The poisoned patient with altered consciousness. Controversies in the use of a 'coma cocktail'. JAMA. Aug 16 1995;274(7):562-9. [Medline].
• Kahn RC, Shechter Y. Insulin, oral hypoglycemic agents, and the pharmacology of the endocrine pancreas. In: Goodman and Gilman's: The Pharmacologic Basis of Therapeutics. 8^th ed. 1993:1463-84.
• Leiken JB, Palouchek FP. Poisoning and Toxicology Handbook. 1996-1997.
• Martin FI, Hansen N, Warne GL. Attempted suicide by insulin overdose in insulin-requiring diabetics. Med J Aust. Jan 15 1977;1(3):58-60. [Medline].
• McEvoy GK. Drug Information. 1986.
• Paterson KR, Paice BJ, Lawson DH. Undesired effects of biguanide therapy. Adverse Drug React Acute Poisoning Rev. 1984;3(3):173-82. [Medline].
• Patrick AW, Williams G. Adverse effects of exogenous insulin. Clinical features, management and prevention. Drug Saf. Jun 1993;8(6):427-44. [Medline].
• Ragland G. Hypoglycemia. In: Tintinalli J, et al, eds. Emergency Medicine: A Comprehensive Study Guide. 1996:939-46.

Article Last Updated: Nov 26, 2008