Abnormalities in the secretion of counterregulatory hormonesthat produce hypoglycemia usually involve GH, cortisol, orboth. Deficiencies in glucagon and epinephrine secretion arerare. GH and cortisol deficiency occur as a result of hypopituitarism. Hypopituitarism results from congenital hypoplasiaor aplasia of the pituitary or, more commonly, from deficiencyof hypothalamic releasing factors (see Chapter 173). Clues tothis diagnosis in infants include the presence of hypoglycemia in association with midline facial or neurologic defects(e.g., cleft lip and palate or absence of the corpus callosum), pendular (roving) nystagmus (indicating visual impairment frompossible abnormalities in the development of the optic nerves,
Heart, kidney, muscle, brain
Brain, blood cells
Figure 172-1 Regulation of serum glucose.
represents inhibitions. EPI, Epinephrine; FFA, free fatty acid; GH, growth hormone; TG, triglyceride.
which can occur in septo-optic dysplasia), and the presence ofmicrophallus and cryptorchidism in boys (indicating abnormalities in gonadotropin secretion). Jaundice and hepatomegaly alsocan occur, simulating neonatal hepatitis. Despite the presence ofGH deficiency, these infants are usually of normal size at birth.
Deficient cortisol secretion also can occur in primary adrenal insufficiency, resulting from a variety of causes. In infants it often results from congenital adrenal hyperplasia, most frequently as a result of 21-hydroxylase deficiency (see Chapters 177 and 178). In older children, primary adrenal insufficiency is seen most frequently in Addison disease and other disorders (see Chapter 178).
Confirmation of GH or cortisol deficiency as the cause of hypoglycemia requires the detection of low serum GH and cortisol concentrations during an episode of hypoglycemia or after other stimulatory testing. In contrast to hyperinsulinism, serum and urine ketones are positive at the time of hypoglycemia and FFAs are elevated. Treatment involves supplementation of the deficient hormones in physiologic doses.
Sufficient energy stores in the form of glycogen, adipose tissue, and muscle are necessary to respond appropriately to hypoglycemia. Deficiencies in these stores are a common cause of hypoglycemia in neonates who are small for gestational age or premature (see Chapter 60). Beyond the early neonatal period, energy stores are usually sufficient to meet the metabolic requirements except in malnourished children.
A common cause of new-onset hypoglycemia is idiopathicketotic hypoglycemia, usually seen in children between 18months and 5 years of age. Patients have symptoms of hypoglycemia after a period of prolonged fasting, often in the settingof an intercurrent illness with decreased feeding. Children withthis disorder are often thin and small and may have a history ofbeing small for gestational age. Defective mobilization of alanine from muscle to fuel gluconeogenesis is thought to be the cause, although the condition may derive mostly from havinglower fuel reserves. Because there are no specific diagnostic testsfor this disorder, ketotic hypoglycemia is a diagnosis of exclusion.
Treatment involves avoidance of fasting and frequent feedings of a high-protein, high-carbohydrate diet. Patients may require hospitalization for IV glucose infusion if they cannot maintain adequate oral intake during a period of illness. The disorder usually resolves spontaneously by 7 to 8 years of age.
Maintenance of normal serum glucose concentrations in thefasting state requires glucose production via glycogenolysisand gluconeogenesis and the production of alternative energysources (FFAs and ketones) via lipolysis and fatty acid oxidation.