PATHOPHYSIOLOGY

Normal plasma glucose is maintained by the complex interaction of hormones that regulate the production and utilization of glucose. Glucose is produced from the breakdown of glycogen stores or from conversion of alternate substrates to glucose.

The clinical manifestations of hypoglycemia can be divided into two categories: those associated with activation of the autonomic nervous system and those associated with decreased glucose utilization by the brain. At blood glucose levels between 50 and 70 mg/dL, autonomic symptoms including diaphoresis, tachycardia, tremulousness, weakness, dizziness, pallor, nausea, and hunger are generally found. At blood glucose levels less than 50 mg/dL, neuroglycopenic symptoms, including lethargy, irritability, confusion, abnormal behavior, seizure, and coma can be seen. Recurrent episodes of hypoglycemia may lead to developmental delays, learning disabilities, and behavioral problems.

The history in a hypoglycemic patient can provide important clues to the underlying cause of abnormal glucose homeostasis. First, it is critical to determine whether the hypoglycemia occurs during a fed or a fasting state. If the child develops hypoglycemia just after eating, the specific contents of the preceding meal may provide clues to the underlying problem. For example, children with galactosemia or defects of organic acid metabolism may develop hypoglycemia shortly after consuming milk products or protein, respectively. Inquiring about food aversions may be helpful, as many children learn to avoid foods that make them sick. Given the predictability of the processes that maintain plasma glucose based on duration of fast (Table 27-1), one can gain additional diagnostic clues based on the time since previous meal. A notable increase in the typical duration of fasting occurs as infants consolidate their overnight sleep; infants may present with new-onset hypoglycemia during this transition period.

The child’s past medical history should also be thoroughly explored. Birth history should be gathered, as being large for gestational age suggests hyperinsulinemia. If prior episodes of hypoglycemia have occurred, it is important to determine the age of onset. Inborn errors of metabolism generally present within the first 2 years of life, whereas ketotic hypoglycemia, cortisol deficiency, and growth hormone deficiency generally present after 1 year of age. The possibility of past hypoglycemic episodes that were not diagnosed as such should also be considered; a history of unexplained seizures or recurrent respiratory infections (hyperventilation secondary to metabolic acidosis) may actually represent episodes of hypoglycemia. Children who are hypoglycemic after an overnight fast may awaken irritable or lethargic or request juice upon awakening. A careful developmental history should be obtained, because recurrent or prolonged hypoglycemia may manifest as delayed acquisition of milestones.

The patient’s family history may provide clues to a hereditary cause of hypoglycemia. In particular, it is important to inquire about a history of Reye syndrome, sudden infant death syndrome (or unexplained childhood death), and other family members with hypoglycemia, as this may suggest an inborn error of metabolism.

Finally, a history of ingestions should also be considered, particularly in young children. Hypoglycemia can be secondary to the consumption of alcohol, oral hypoglycemic agents, β-adrenergic blockers, aspirin, or other substances.

In addition to performing a thorough physical examination, clinicians should pay particular attention to specific physical findings that can provide diagnostic clues in children with hypoglycemia. Table 27-2 highlights some of these physical findings.