Hyperinsulinemia

- the most common cause of persistent hypoglycemia in early infancy.
- may be macrosomic (anabolic effects of ~ in utero)
- onset is from birth to 18 mo,depending on severity
- when less severe, hypoglycemia may appear after the first few weeks to mos, when feeding is less frequent i.e esp overnight, and hyperinsulinemia prevents mobilization of endogenous glucose
- steroids or diazoxide (a HTN med) can increase blood glucose levels.

Common presenting features
- increasing appetite/demand for feeds
- wilting spells
- jitteriness
- frank seizures

Lab indicators
- rapid development of fasting hypoglycemia after 4-8 hours (vs other cause of hypoglycemia, ie in nonhyperinsulemic causes, it takes on average 18 hours fasting to reach hypoglycemia, vs 2.1 hrous.
- need for high rates of glucoes infusion, often > 10-15 mg/kg/min
- absence of ketonemia or acidosis
- elevated c-peptide  or proinsulin levels at time of hypoglycemia.
- there will usually be a good response to glucagon (increase by 40 mg/dL glucose) implying that although insulin restrains glucose mobilization, glycogenolytic mechs are still intact.

Useful tests
- IGF BP-1. Secretion is acutely inhibited by insulin; concentrations are low during hyperinsulinism induced hypoglycemia. In normal hypoglycemic patients (ie fasting) IGF BP-1 levels should be higher, because insulin levels should be low.

DDX
- once endogenous hyperinsulinism has been established through measurements taken at the time of spontaneous or fasting hypoglycemia, the ddx includes:

• familial and non-familial hyperinsulinism of infancy
• B-cell hyperplasia or adenoma

Congenital hyperinsulinism (or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), formerly called nesidioblastosis) can be broken down into three entities

• autosomal recessive, defective K+-channel regulation associated with insulin secr by B-cell
• autsomal dominant, less severe clinical features, presenting later i.e usually @ 1 year, and even as delayed as age 30.
• sporadic/auto dominant: assoc with mild hyper ammonemia. Diet and diazoxide control sx, but pancratectomy may be indicated.

Leucine-sensitive hypoglycemia is a from of the hyperinsulinemia-hyperammonemia syndrome. Leucine is a potent amino acid for stimulating insulin secretion.

r/o Munchausen syndrome by proxy

Beckwith Wiedemann
Soto Syndrome

After the first 12 mo of life, hyperinsulinemic states are uncommmon until islet cell adenomas appear. Consider this dx in any child older than 5 years presenting with hypoglycemia. Consider MEN Type I (multiple endocrine adenomatosis) Wermer syndrome

Rare association with hypoglycemia: antibodies to insulin or the insulin receptor.