What is the appropriate workup for hypoglycemia (low blood sugar)?

From the Guidelines

The workup for hypoglycemia should begin with a thorough history and physical examination, followed by laboratory testing during a hypoglycemic episode using Whipple's triad (symptoms of hypoglycemia, low plasma glucose, and resolution of symptoms after glucose administration) as recommended by the most recent guidelines 1. The initial step in evaluating hypoglycemia is to assess the patient's symptoms, medical history, and current medications, as certain medications such as insulin or sulfonylureas can increase the risk of hypoglycemia 1.

Key Components of Hypoglycemia Workup

• A comprehensive metabolic panel, complete blood count, insulin level, C-peptide, proinsulin, beta-hydroxybutyrate, sulfonylurea screen, and antibodies against insulin should be included in the initial laboratory tests 1.
• For suspected reactive hypoglycemia, a 5-hour oral glucose tolerance test may be appropriate, while a supervised 72-hour fast is the gold standard diagnostic test for suspected insulinoma or other causes of fasting hypoglycemia 1.
• Imaging studies such as CT, MRI, or endoscopic ultrasound may be necessary if an insulinoma is suspected, and additional testing should be tailored to the clinical context, including cortisol levels for suspected adrenal insufficiency, growth hormone for hypopituitarism, or liver function tests for hepatic dysfunction 1.

Importance of Recent Guidelines

The most recent guidelines from 2023 emphasize the importance of reviewing the occurrence and risk for hypoglycemia at every encounter and investigating as indicated, using validated tools to assess awareness of hypoglycemia 1.

Treatment and Prevention

Glucose (approximately 15–20 g) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L), although any form of carbohydrate that contains glucose may be used 1. Glucagon should be prescribed for all individuals at increased risk of level 2 or 3 hypoglycemia, and caregivers or family members should know how to administer it 1. Hypoglycemia unawareness or one or more episodes of level 3 hypoglycemia should trigger hypoglycemia avoidance education and reevaluation and adjustment of the treatment plan to decrease hypoglycemia 1. Insulin-treated patients with hypoglycemia unawareness, one level 3 hypoglycemic event, or a pattern of unexplained level 2 hypoglycemia should be advised to raise their glycemic targets to strictly avoid hypoglycemia for at least several weeks 1. Ongoing assessment of cognitive function is suggested with increased vigilance for hypoglycemia by the clinician, patient, and caregivers if impaired or declining cognition is found 1.

From the Research

Hypoglycemia Workup

• The evaluation and management of adults with hypoglycemic disorders, including those with diabetes mellitus, is crucial 2.
• The Endocrine Society Clinical Practice Guideline recommends evaluating and managing hypoglycemia only in patients who meet Whipple's triad: symptoms, signs, or both consistent with hypoglycemia, a low plasma glucose concentration, and resolution of those symptoms or signs after the plasma glucose concentration is raised 2.
• In patients with hypoglycemia without diabetes mellitus, the differential diagnosis includes accidental, surreptitious, or malicious hypoglycemia, endogenous hyperinsulinism, and other potential causes 2.
• Laboratory tests, such as plasma glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, and circulating oral hypoglycemic agents, can help diagnose endogenous hyperinsulinism during an episode of hypoglycemia 2.

Documentation of Hypoglycemia Assessment

• A retrospective cohort study found that documentation of hypoglycemia assessment was significantly more prevalent among patients seen in endocrinology clinics than in primary care clinics 3.
• The study also found that hypoglycemia was identified by patients in 38.2% of encounters, and treatment was modified in 30% of primary care and 46% of endocrinology clinic encounters 3.
• The odds of hypoglycemia assessment documentation were highest among patients treated with hypoglycemia-prone medications and those seen in endocrinology clinics 3.

Laboratory Tests for Hypoglycemia

• While basic metabolic panels and complete blood counts can provide valuable information on electrolyte imbalances and metabolic disorders, they are not directly related to hypoglycemia workup 4, 5, 6.
• However, these tests can help identify underlying conditions that may contribute to hypoglycemia, such as kidney disorders or metabolic syndrome 4, 5, 6.