When a Child Comes to the Emergency Department Altered...

Donna Moro-Sutherland, MD; Ghazala Sharieff, MD


July 30, 2010


Teaching Points: Hypoglycemia With Non-Anion Gap Acidosis

The precise definition of hypoglycemia in infants and children continues to be controversial. Most agree that a plasma glucose level < 35-45 mg/dL in neonates and a plasma glucose level < 55 mg/dL in children defines hypoglycemia. The symptoms of hypoglycemia can be divided into 2 categories: autonomic response and neuroglycopenia.

During the autonomic response to hypoglycemia, the child may appear weak, sweating, tachycardic, and tremulous, with feelings of nervousness or hunger. These symptoms are generally apparent when the glucose concentration is between 40 and 70 mg/dL.

The neuroglycopenic stage generally occurs after prolonged hypoglycemia with serum glucose level < 50 mg/dL. Symptoms include lethargy, irritability, and confusion or behavior that is out of character for the child. In extreme cases, the child may experience seizures and coma.

Immediate management involves obtaining critical samples and administering parenteral glucose, especially when serum glucose level is ≤ 40 mg/dL.

Blood tests that should be drawn immediately include:

  • Glucose;

  • Lactate;

  • Insulin, cortisol, growth hormone, C-peptide, total and free carnitine, acylcarnitine profile; and

  • Beta hydroxybutyrate

Other tests that are helpful include:

  • Serum electrolytes (for calculation of anion gap);

  • Liver function tests;

  • Ammonia;

  • Toxicology studies (ie, salicylates, ethanol, and sulfonylurea);

  • Serum amino acids; and

  • Urinalysis (for ketones, reducing substances, and urine organic acid analysis)

A good starting point for evaluating hypoglycemia is to determine whether the patient has ketotic or nonketotic hypoglycemia (Table 1).

Table 1. Differential Diagnosis of Hypoglycemia

Ketotic Hypoglycemia Nonketotic Hypoglycemia
Endocrine deficiencies: primary or secondary adrenal insufficiency, pituitary disturbances (ie, GH or ACTH deficiency), and hypothyroidism Hyperinsulinemia: islet cell adenomas, islet cell dysplasia; typically presents in the first year of life.
Idiopathic ketotic hypoglycemia: most common form of childhood hypoglycemia; presents between age 19 months and 5 years, and remits before age 8-9 years Disorders of gluconeogenesis: fructose-1,6-diphosphatase deficiency, galactosemia
Organic aciduria: anion gap metabolic acidosis, ketosis, elevated lactate level, neutropenia, thrombocytopenia Defects in fatty acid metabolism: MCAD, VLCAD
Glycogen storage disorders  

ACTH = adrenocorticotropin hormone; GH = growth hormone; MCAD = medium-chain acyl-CoA dehydrogenase deficiency; VLCAD = very-long-chain acyl-CoA dehydrogenase deficiency

What about the serum anion gap?
Children with metabolic acidosis can be classified into 2 groups on the basis of the serum anion gap: a normal anion gap and an elevated anion gap metabolic acidosis. The following mnemonics may help emergency physicians direct the care of their patients (Table 2).

Table 2. Causes of Metabolic Acidosis

Elevated Anion Gap Acidosis: MUDPILES Normal Anion Gap Acidosis: USEDCARP
M: Methanol U: Ureterostomy
U: Uremia S: Small bowel fistulas
D: Diabetic ketoacidosis, Diarrheal dehydration E: Extra chloride (hyperalimentation)
P: Paraldehyde D: Diarrhea
I: Inborn errors of metabolism, Iron, Isoniazid C: Carbonic anhydrase inhibitors (acetazolamide)
L: Lactic acidosis (hypoxia, sepsis, idiopathic) A: Adrenal insufficiency
E: Ethanol, Ethylene glycol R: Renal tubular acidosis
S: Salicylates P: Pancreatic fistula

The anion gap, especially if elevated, can help direct laboratory evaluation and management. It is less helpful if the history does not support many of the causes for a normal anion gap acidosis. For the patient in this case, the normal anion gap acidosis helped to exclude several of the early considerations (ie, inborn errors of metabolism) in the ED.

All emergency physicians have had a child present to the ED with ketotic hypoglycemia. An extensive workup is initiated each time, only to find out that the ultimate cause remains unknown. The hypoglycemia occurs in association with an intercurrent infection or at times of fasting for 12 hours or more. The child's symptoms resolve after the administration of glucose in the ED.

Final Diagnosis: Idiopathic Ketotic Hypoglycemia

Idiopathic ketotic hypoglycemia (IKH) is a physiologic process in which children experience an unusual degree of episodic hypoglycemia after a brief period of caloric deprivation. It is felt to be the most common cause of hypoglycemia in childhood and occurs most commonly in children age 19 months to 5 years. Symptoms typically remit spontaneously by 8-9 years of age. Children generally present in the morning hours after a fast of 10-16 hours. These children are often experiencing an intercurrent illness (eg, upper respiratory tract infection) at the time of presentation. Symptoms associated with IKH include weakness, palpitations, tremulousness, nausea, sweating, headache, anxiety, and personality changes. In a study by Dalyand colleagues,[1] children were found most often to have generalized lethargy. Symptoms included sleepiness, fatigue, decreased energy, or inability to awaken normally from sleep. The management of IKH involves preventing future episodes of hypoglycemia, especially during times when the child is most vulnerable. One recommendation involves frequent meals, achieving adequate hydration with sugar-containing fluids if the child is vomiting, and bringing the child promptly to medical attention when symptoms of hypoglycemia are exhibited.


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