para />
Usually divided into two syndromes
Screening infants for hypoglycemia is appropriate when pregnancy was complicated by maternal diabetes.
Cases of hypoglycemia observed in children taking propranolol for infantile hemangioma
Associated with indomethacin when treating patent ductus arteriosus
Geriatric Considerations
COMMONLY ASSOCIATED CONDITIONS
- Severe liver disease; alcoholism
- Addison disease; adrenocortical insufficiency
- Myxedema
- Malnutrition (patients with renal failure)
- GI surgery
- Panhypopituitarism
- Insulinoma
DIAGNOSIS
HISTORY
- CNS (neuroglycopenic) symptoms predominate with gradual glucose reduction:
- Headache
- Confusion
- Light-headedness
- Fatigue and weakness
- Visual disturbances
- Changes in personality
- Adrenergic symptoms: more prominent in acute drop in glucose
- Anxiety
- Tremulousness
- Dizziness
- Diaphoresis
- Warmth/flushing
- Heart palpitations
- GI symptoms
PHYSICAL EXAM
- CNS (neuroglycopenic) symptoms predominate with gradual glucose reduction:
- Convulsions
- Coma
- Hypotension
- Adrenergic symptoms: more prominent in acute drop in glucose
- Tremulousness
- Diaphoresis
- Warmth/flushing
- Heart palpitations
DIFFERENTIAL DIAGNOSIS
CNS disorders
- Psychogenic
- Pseudohypoglycemia: Symptoms of hypoglycemia or self-diagnosis in patients in whom low blood glucose may not be detectable and may be impossible to convince that they do not suffer from hypoglycemia after all tests are found to be normal.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Blood glucose ≤45 mg/dL (≤2.5 mmol/L) when symptomatic followed by symptom resolution with feeding (2)[C]
- Plasma glucose overnight fasting: ≤60 mg/dL (≤3.33 mmol/L); confirm on ≥2 occasions (2)[C].
- Plasma glucose 72-hour fasting: ≤45 mg/dL (≤2.5 mmol/L) for females; ≤55 mg/dL (≤3.05 mmol/L) for males; fasting may be ended when Whipple triad is achieved or hypoglycemia is demonstrated (2)[C].
- Abdominal CT to rule out abdominal tumor
Follow-Up Tests & Special Considerations
- Misinterpretation of glucose tolerance tests may lead to misdiagnosis of hypoglycemia; ≥1/3 of normal patients have hypoglycemia, with or without symptoms, during the 4-hour glucose tolerance test. These patients may be at future risk for type 2 diabetes.
- C-peptide measurement (2)[C]
- Check liver studies, serum insulin, adrenocorticotrophic hormone (ACTH), and cortisol. Serum insulin should be suppressed when glucose is <60 mg/dL.
- Serum β-hydroxybutyrate (2)[C]
- Insulin radioimmunoassay: Elevated insulin levels suggest islet cell hyperplasia or tumor.
- Drugs that may alter lab results: Many drugs can affect glucose levels; refer to drug or laboratory reference.
Diagnostic Procedures/Other
- For definitive diagnosis, patient should have
- Documented low glucose levels
- Symptoms when glucose levels are low
- Evidence that symptoms are relieved specifically by ingestion of sugar or other food
- Identification of the specific type of hypoglycemia
- Serum β-hydroxybutyrate <2.7 mg/dL in the presence of high serum insulin, C-peptide, and low serum glucose suggests excessive insulin production (2)[C].
TREATMENT
GENERAL MEASURES
- Outpatient except for severe cases; may also be inpatient for testing
- Oral carbohydrate for alert patient without drug overdose (2 to 3 tbsp of sugar in glass of water or fruit juice, 1 to 2 cups of milk, piece of fruit, or several soda crackers)
- If unable to swallow: Use glucagon IM or SC.
- If caused by medication or nutrients: Avoid or control causative agents.
- If triggered by meals: Try high-protein diet with carbohydrate restriction.
- Nonhypoglycemic hypoglycemia or pseudohypoglycemia
- Many patients (often women aged 20 to 45 years) present with diagnosis of reactive hypoglycemia (self-diagnosed or misinterpretation of tests).
- Symptoms may pertain to chronic fatigue and somatic complaints (stress often plays a role in these symptoms).
- Management difficult; listening is important. Try 120-g carbohydrate diet.
- Counseling may be useful for stress and other problems.
MEDICATION
- Once diagnosis is established, begin therapy appropriate for underlying disorder.
- If unable to swallow: glucagon 1 mg (1 unit) IM or SC. If no response, give IV bolus of 25 to 50 g of 50% glucose solution followed by continuous infusion until patient able to take by mouth.
- Postsurgical gastrectomy patients unresponsive to dietary changes may benefit from propantheline, psyllium, fiber, or oat bran, which delays gastric emptying.
- Insulinoma
SURGERY/OTHER PROCEDURES
If islet cell tumor (insulinoma) or other insulin-secreting tumor, surgery is treatment of choice; if inoperable, diazoxide may relieve symptoms (1)[C].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Hypoglycemia unresponsive to oral intake
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Exercise routine or daily activity may need to be reevaluated.
- Patients with recurrent hypoglycemia should have glucose source at hand for immediate ingestion during symptoms.
Patient Monitoring
- Depends on type and severity of symptoms and treatment of underlying cause
- Hypoglycemia from sulfonylureas can last for hours to days depending on half-life and renal function.
DIET
- High protein, high fiber, complex carbohydrates from multigrain, and whole foods in moderation
- Frequent small feedings (six daily)
- Avoid fasting.
PATIENT EDUCATION
- Dietary instruction
- Counseling for stress, if appropriate
- Recognition of early symptoms of hypoglycemia and how to take corrective action
PROGNOSIS
Favorable, with appropriate treatment
COMPLICATIONS
- Insulinoma: If tumor identified and removed, some surgical risk is involved.
- Organic brain syndrome: may occur with extensive, prolonged hypoglycaemia
REFERENCES
11 Guettier JM, Gorden P. Hypoglycemia. Endocrinol Metab Clin North Am. 2006;35(4):753-766.22 Service FJ. Hypoglycemic disorders. N Engl J Med. 1995;332(17):1144-1152.33 Kagansky N, Levy S, Rimon E, et al. Hypoglycemia as a predictor of mortality in hospitalized elderly patients. Arch Intern Med. 2003;163(15):1825-1829.44 Mannucci E, Monami M, Mannucci M, et al. Incidence and prognostic significance of hypoglycemia in hospitalized non-diabetic elderly patients. Aging Clin Exp Res. 2006;18(5):446-451.55 Nirantharakumar K, Marshall T, Hodson J, et al. Hypoglycemia in non-diabetic in-patients: clinical or criminal? PLoS One. 2012;7(7):e40384.66 Ben Salem C, Fathallah N, Hmouda H, et al. Drug-induced hypoglycaemia: an update. Drug Saf. 2011;34(1):21-45.
ADDITIONAL READING
- Bharmal SV, Moyes V, Ahmed S, et al. Hypoglycaemia: possible mediation by chromium salt medication. Hormones (Athens). 2010;9(2):181-183.
- Cansu DU, Korkmaz C. Hypoglycaemia induced by hydroxychloroquine in a non-diabetic patient treated for RA. Rheumatology (Oxford). 2008;47(3):378-379.
- Chan TY. Outbreaks of severe hypoglycaemia due to illegal sexual enhancement products containing undeclared glibenclamide. Pharmacoepidemiol Drug Saf. 2009;18(12):1250-1251.
- Lawrence KR, Adra M, Keir C. Hypoglycemia-induced anoxic brain injury possibly associated with levofloxacin. J Infect. 2006;52(6):e177-e180.
- Pollak PT, Mukherjee SD, Fraser AD. Sertraline-induced hypoglycemia. Ann Pharmacother. 2001;35(11):1371-1374.
- Singh M, Jacob JJ, Kapoor R, et al. Fatal hypoglycemia with levofloxacin use in an elderly patient in the post-operative period. Langenbecks Arch Surg. 2008;393(2):235-238.
- Yamada C, Nagashima K, Takahashi A, et al. Gatifloxacin acutely stimulates insulin secretion and chronically suppresses insulin biosynthesis. Eur J Pharmacol. 2006;553(1-3):67-72.
SEE ALSO
- Hypoglycemia, Diabetic; Insulinoma
- Algorithm: Hypoglycemia
CODES
ICD10
- E16.2 Hypoglycemia, unspecified
- E16.1 Other hypoglycemia
- P70.4 Other neonatal hypoglycemia
- E16.0 Drug-induced hypoglycemia without coma
ICD9
- 251.2 Hypoglycemia, unspecified
- 579.3 Other and unspecified postsurgical nonabsorption
- 775.6 Neonatal hypoglycemia
- 251.1 Other specified hypoglycemia
SNOMED
- 302866003 Hypoglycemia (disorder)
- 197483008 Post gastrointestinal tract surgery hypoglycemia (disorder)
- 52767006 Neonatal hypoglycemia (disorder)
- 237639008 Alimentary hypoglycemia (disorder)
CLINICAL PEARLS
- Symptoms coincide with low blood glucose levels and resolve with PO/IV glucose or glucagon.
- Avoid known agents/nutrients that trigger hypoglycemia.
- Treat underlying cause.