Approach to hypoglycemia (pediatrics): Clinical sciences

Hypoglycemia refers to a plasma glucose concentration that’s less than the lower limit of normal for age. Because the brain primarily relies on glucose as an energy source, prolonged hypoglycemia can cause serious adverse effects, such as seizures and permanent brain injury.

Infants less than 48 hours old frequently have transient physiologic hypoglycemia, while persistent hypoglycemia beyond 48 hours of life can be caused by medications or substances, as well as conditions unique to infancy and childhood, including inborn errors of carbohydrate metabolism, hypopituitarism, hyperinsulinism, fatty acid oxidation defects, disorders of gluconeogenesis, and ketotic hypoglycemic disorders.

Now, if a pediatric patient presents with hypoglycemia, you should first perform an ABCDE assessment to determine if your patient is unstable or stable. If unstable, stabilize the airway, breathing, and circulation. Next, obtain a fingerstick or heel stick glucose level, and obtain IV access to give IV dextrose. In addition, begin continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. Finally, if needed, provide supplemental oxygen.

Here’s a clinical pearl! Be sure to consider sepsis in a newborn infant with hypoglycemia, especially if they are unstable or have temperature instability.

Now, let’s go back to the ABCDE assessment and discuss stable patients. In this case, first, obtain a focused history and physical examination, as well as bedside glucose followed by a critical lab sample to confirm the plasma glucose level. Clinical manifestations of hypoglycemia differ based on age, with newborns and infants displaying symptoms like poor feeding, lethargy, or irritability; while an older child may report weakness, drowsiness, confusion, or hunger.

Meanwhile, the physical exam in a newborn or infant might reveal pallor, jitteriness, and occasionally, seizures; while an older child may display confusion, diaphoresis, or weakness. In both cases, the bedside glucose will be less than 50 to 60 milligrams per deciliter. Finally, if the plasma glucose is less than 50 milligrams per deciliter in newborns under 48 hours of age, and less than 60 milligrams per deciliter in infants or children over 48 hours of age, you can diagnose hypoglycemia.

Here’s a clinical pearl! Hypoglycemic disorders are much less common in older children, so always assess verbal patients for the Whipple triad before beginning further evaluation. Criteria include a documented low plasma glucose concentration, signs or symptoms consistent with hypoglycemia, and relief of those signs or symptoms after ingesting glucose.

Once you diagnose hypoglycemia, your first step is to assess your patient’s age. For infants less than 48 hours old, consider transient hypoglycemia, which is common in the first 2 days of life due to transient physiologic hyperinsulinism. These infants are often small or large for gestational age, preterm, or infants of a diabetic mother.

In this case, give your patient glucose, either by feeding the infant, or by giving IV dextrose if they are unable to feed. Next, reassess the blood glucose level after 48 hours of age. If the hypoglycemia has resolved by that time, diagnose transient hypoglycemia of the newborn.

On the other hand, hypoglycemia that persists after 48 hours of age is likely to be pathologic, so in this case you should consider a persistent hypoglycemic disorder.

Before we proceed with an evaluation, let’s go back and discuss hypoglycemic patients who present after 48 hours of age. In these patients, consider the possibility of medication or other substance effects, especially if your patient has diabetes. Some common medications associated with hypoglycemia include insulin, sulfonylureas, or beta-blockers. Additionally, alcohol ingestion frequently causes hypoglycemia in children, since it’s often found in mouthwash and can be accidentally ingested. If there’s a known or suspected ingestion of any, your patient is likely dealing with medication- or substance-induced hypoglycemia!

On the flip side, if you rule out medications and substances associated with hypoglycemia, you should consider a persistent hypoglycemic disorder. In this case, begin your workup by assessing the timing of hypoglycemia in relation to a feeding, since this can provide clues to the underlying cause.

If your patient’s hypoglycemia is only postprandial, consider an inborn error of carbohydrate metabolism. Your next step is to order labs, including urine non-glucose reducing substances and molecular genetic testing, and don’t forget to review your patient’s newborn screen results, if available. Now, if urine non-glucose reducing substances are positive, and the newborn screen detects no GALT activity, you can diagnose galactosemia. However, if urine non-glucose reducing substances are positive, and genetic testing confirms a mutation of ALDOB, diagnose hereditary fructose intolerance.

Now, let’s switch gears and consider cases in which hypoglycemia occurs randomly or during a period of fasting. In this case, your first step is to order labs, including a comprehensive metabolic panel, or CMP; serum ketones, which are typically measured as beta-hydroxybutyrate; as well as lactate and free fatty acids. During your workup, be sure to collect blood samples during an episode of hypoglycemia!

Next, assess whether or not there’s acidosis. If the serum bicarbonate is 18 milliequivalents per liter or greater, there’s no acidosis, so look for features suggestive of hypopituitarism. These include midline defects, such as cleft lip and palate, cholestatic jaundice, and microphallus if your patient is biologically male.

If any of these features are present, consider hypopituitarism, and check serum IGF-1 and cortisol levels. If they’re both low, order provocative tests of both growth hormone and ACTH secretion, as well as an MRI of the brain. Inadequate hormone response to stimulation as well as MRI findings demonstrating a pituitary defect, such as an absent septum pellucidum, confirms congenital hypopituitarism.