Hypoglycemia

Published on 06/06/2015 by admin

Filed under Pediatrics

Last modified 06/06/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 846 times

72 Hypoglycemia

Hypoglycemia is often the initial manifestation of a disorder of energy metabolism and regulation. The accurate diagnosis of the underlying condition facilitates institution of disease-specific therapy that can prevent long-term complications such as seizures, developmental delay, permanent brain damage, and even death. In children, the most common cause of persistent hypoglycemia is hyperinsulinism, a disorder affecting approximately 1 in 20,000 children in the United States.

Etiology and Pathogenesis

In children, as in adults, blood glucose levels are maintained within a narrow range in the postabsorptive and fed state. Thus, normal fasting blood glucose levels should be above 70 mg/dL. A lower level of 50 mg/dL is recommended for diagnostic purposes only. The classic diagnostic triad of hypoglycemia, also known as “Whipple’s triad,” consists of a blood glucose level less than 50 mg/dL, symptoms of hypoglycemia, and resolution of symptoms with normalization of the blood glucose level.

To recognize the different causes of hypoglycemia, it is helpful to understand the fundamentals of energy homeostasis (Figure 72-1). In the fed state, as glucose levels increase, so do insulin levels. Insulin stimulates glucose uptake into cells for use as a source of energy and metabolic intermediate or for storage (see Chapter 4, Figure 4-1). Insulin has other effects that influence energy metabolism; in the liver, insulin inhibits glycogenolysis, gluconeogenesis, and ketogenesis. In the fasted state, insulin secretion is suppressed, allowing glycogenolysis and gluconeogenesis to commence, followed by fatty-acid oxidation, which leads to ketogenesis. In the absence of glucose, the brain uses ketones (e.g., β-hydroxybutyrate and acetoacetate) as energy sources. Insulin secretion from pancreatic β-islet cells is suppressed in the fasted state, and there is increased secretion of counterregulatory hormones that maintain blood glucose levels by stimulating glycogenolysis and gluconeogenesis, such as glucagon, cortisol, growth hormone, and epinephrine. Disorders that impair insulin regulation and counterregulatory hormone secretion, as well as storage or production of glucose, can result in hypoglycemia.

Clinical Presentation

The symptoms of hypoglycemia can result from two different mechanisms. An adrenergic response (e.g., fight or flight) typically is triggered in response to a rapid decrease in blood glucose, as occurs with postprandial hypoglycemia (PPH). By contrast, the slower decline in blood glucose that occurs with fasting hypoglycemia may not trigger an obvious adrenergic response but can manifest as loss of consciousness caused by neuroglycopenia (Figure 72-2). In general, hypoglycemia in infants and children is fasting hypoglycemia. Hypoglycemia in neonates can present with irritability, shakiness, difficulty feeding, hypothermia, pallor, hypotonia, and seizures. In children, symptoms include sweatiness, unsteadiness, headache, hunger, nausea, weakness, tachycardia, change in mentation, and seizures. If symptoms suggestive of hypoglycemia are present, it is imperative, if possible, to send a blood specimen for a glucose level to the laboratory to confirm that hypoglycemia is at the root of the symptoms.

Differential Diagnosis

The differential diagnosis of hypoglycemia is expansive and includes not only disorders of carbohydrate metabolism but also disorders of fat oxidation, hormone deficiencies, and medication-induced hypoglycemia (Box 72-1). It is perhaps most useful to separate these disorders into those associated with hyperinsulinism and those associated with appropriately suppressed levels of insulin. Not included in this classification is transient neonatal hypoglycemia, typically seen within the first 6 hours of life, caused by immaturity of fasting mechanisms and poor glucose stores in premature infants and breastfed infants. In these cases, the hypoglycemia improves with feedings and typically resolves within the first day of life.

Box 72-1 Differential Diagnosis of Hypoglycemia in Infants and Children

ATCH, adrenocorticotropic hormone; F-1,6-Pase, fructose-1,6-biphosphatase; GDH, glutamate dehydrogenase; GSD 0, glycogen synthase deficiency; GSD 1a, glucose-6-phosphatase deficiency; GSD 1b, glucose-6-phosphate translocase deficiency; GSD 3; debrancher enzyme deficiency; GSD 6, glycogen phosphorylase deficiency; GSD 9, phosphorylase kinase deficiency; KATP, adenosine triphosphate–sensitive potassium; PPH, postprandial hypoglycemia; SCHAD, short-chain 3-hydroxyacyl-CoA dehydrogenase.

Hypoglycemia Secondary to Excessive and Inappropriate Insulin

Permanent Hypoglycemia (Congenital Hyperinsulinism)

The most common cause of persistent hypoglycemia in infants and children is congenital hyperinsulinism (CHI). In general, infants with CHI are large for gestational age and develop severe hypoglycemia shortly after birth. They require large amounts of intravenous (IV) glucose to maintain blood glucose above 70 mg/dL. During hypoglycemia (blood glucose <50 mg/dL), these infants have inappropriately normal or elevated serum insulin levels (although insulin levels may not be detected in all assays), suppressed free fatty acids and β-hydroxybutyrate, and a glycemic response to glucagon. Additional laboratory tests that may help distinguish specific forms of hyperinsulinism include ammonia (glutamate dehydrogenase hyperinsulinism), 3-hydroxy-butyrylcarnitine (short chain 3-hydroxacyl Co-A dehydrogenase hyperinsulinism), and abnormally processed transferrin (congenital disorders of glycosylation). Mutations in at least six genes have been associated with hyperinsulinism: the sulfonylurea receptor 1 (SUR-1), potassium inward rectifying channel (Kir6.2), glucokinase (GK), glutamate dehydrogenase (GDH), short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), and ectopic expression on the β-cell plasma membrane of SLC16A1 (encodes monocarboxylate transporter 1 [MCT1]). Ectopic expression of MCT-1 on the plasma membrane of pancreatic β cells leads to exercise-induced hyperinsulinism.

Buy Membership for Pediatrics Category to continue reading. Learn more here