List of causes of hypoglycemia

Hypoglycemia is a common problem with an increasing incidence in critically ill or extremely low birthweight infants.[1] Its potential association with brain damage and neurodevelopment delay make it an important topic.[1] If not due to maternal hyperglycemia, in most cases it is multifactorial, transient and easily supported. In a minority of cases, hypoglycemia turns out to be due to significant hyperinsulinism, hypopituitarism or an inborn error of metabolism and presents more of a management challenge.[1][2]

• Transient neonatal hypoglycemia
  • Prematurity, intrauterine growth retardation, perinatal asphyxia
  • Maternal hyperglycemia due to diabetes or iatrogenic glucose administration
  • Sepsis
  • Prolonged fasting (e.g., due to inadequate breast milk or condition interfering with feeding)
• Congenital hypopituitarism
• Congenital hyperinsulinism,[1] several types, both transient and persistent
• Inborn errors of carbohydrate metabolism such as glycogen storage disease

Single episodes of hypoglycemia may occur due to gastroenteritis or fasting, but recurrent episodes nearly always indicate either an inborn error of metabolism, congenital hypopituitarism, or congenital hyperinsulinism. A list of common causes:

• Prolonged fasting
  • Diarrheal illness in young children, especially rotavirus gastroenteritis
• Idiopathic ketotic hypoglycemia
• Isolated growth hormone deficiency, hypopituitarism
• Insulin excess
  • Hyperinsulinism due to several congenital disorders of insulin secretion
  • Insulin injected for type 1 diabetes
  • Hyperinsulinism-hyperammonemia syndrome (HIHA) due to glutamate dehydrogenase 1 gene. Can cause intellectual disability and epilepsy in severe cases.[3]
• Gastric dumping syndrome (after gastrointestinal surgery)
• Other congenital metabolic diseases; some of the common include
  • Maple syrup urine disease and other organic acidurias
  • Type 1 glycogen storage disease
  • Type III glycogen storage disease. Can cause less severe hypoglycemia than type I
  • Phosphoenolpyruvate carboxykinase deficiency, causes metabolic acidosis and severe hypoglycemia.
  • Disorders of fatty acid oxidation
  • Medium chain acylCoA dehydrogenase deficiency (MCAD)
  • Familial Leucine sensitive hypoglycemia[4]
• Accidental ingestions including pharmacy misfills
  • Sulfonylureas, propranolol and others
  • Ethanol (mouthwash, alcoholic beverages)

By far, the most common cause of severe hypoglycemia in this age range is insulin injected for type 1 diabetes. Circumstances should provide clues fairly quickly for the new diseases causing severe hypoglycemia. All of the congenital metabolic defects, congenital forms of hyperinsulinism, and congenital hypopituitarism are likely to have already been diagnosed or are unlikely to start causing new hypoglycemia at this age. Body mass is large enough to make starvation hypoglycemia and idiopathic ketotic hypoglycemia quite uncommon. Recurrent mild hypoglycemia may fit a reactive hypoglycemia pattern, but this is also the peak age for idiopathic postprandial syndrome, and recurrent "spells" in this age group can be traced to orthostatic hypotension or hyperventilation as often as demonstrable hypoglycemia.

• Insulin-induced hypoglycemia
  • Insulin injected for type 1 diabetes
  • Factitious insulin injection (Munchausen syndrome)
  • Insulin-secreting pancreatic tumor (Insulinoma)
  • Reactive hypoglycemia and idiopathic postprandial syndrome
• Addison's disease
• Sepsis
• Adams Disease

The incidence of hypoglycemia due to complex drug interactions, especially involving oral hypoglycemic agents and insulin for diabetes, rises with age. Though much rarer, the incidence of insulin-producing tumors also rises with advancing age. Most tumors causing hypoglycemia by mechanisms other than insulin excess occur in adults.

• Insulin-induced hypoglycemia
  • Insulin injected for diabetes
  • Factitious insulin injection (Munchausen syndrome)
  • Excessive effects of oral Anti-diabetic medication, beta-blockers, or drug interactions
  • Insulin-secreting neuroendocrine tumor (insulinoma) of the pancreas
  • Alcohol induced hypoglycemia often linked with ketoacidosis (depletion of NAD+ leads to a block of gluconeogenesis)
  • Alimentary (rapid jejunal emptying with exaggerated insulin response)
    • After gastrectomy dumping syndrome or bowel bypass surgery or resection
  • Reactive hypoglycemia and Idiopathic postprandial syndrome
• Tumor hypoglycemia, Doege-Potter syndrome
• Acquired adrenal insufficiency
• Acquired hypopituitarism
• Immunopathologic hypoglycemia[5]