• CNS (neuroglycopenic) symptoms predominate with gradual glucose reduction:
  • Headache
  • Confusion
  • Lightheadedness
  • 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:
  • Hunger
  • Nausea
  • Belching

• 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

LabInitial Labs Blood glucose ≤45 mg/dL (≤2.5 mmol/L) when symptomatic followed by symptom resolution with feeding (1,2)[C]:

• Plasma glucose overnight fasting: ≤60 mg/dL (≤3.33 mmol/L); confirm on 2 or more 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; fast may be ended when Whipple triad is achieved or hypoglycemia is demonstrated (2)[C]

Follow-Up and Special Considerations

• Oral glucose tolerance: ≤50 mg/dL (≤2.78 mmol/L) (1,2)[C]
• 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 (2)[C].
• Serum b-hydroxybutyrate
• Insulin radioimmunoassay: Elevated insulin levels suggest islet cell hyperplasia or tumor (2)[C].
• Drugs may alter lab results: Many drugs can affect glucose levels; refer to drug or laboratory reference (2)[C].

ImagingInitial Imaging Approach Abdominal CT to rule out abdominal tumor

Diagnostic Procedures/Other

• For definitive diagnosis, patient should have (2)[C]:
  • 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 b-hydroxybutyrate <2.7 mg/dL in the presence of high serum insulin, C-peptide, and low serum glucose suggests excessive insulin production.

CNS disorders:

• Psychogenic
• Pseudohypoglycemia: Symptoms of hypoglycemia or self-diagnosis in patients in whom low blood glucose may not be detectable and who may be impossible to convince that they do not suffer from hypoglycemia after all tests are found to be normal