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Congenital Adrenal Hyperplasia

State mandated newborn screening was initiated in the early 1960's for the identification of infants affected with phenylketonuria. In subsequent years, newborn screening was expanded to include tests for hypothyroidism, galactosemia, hemoglobinopathy and congenital adrenal hyperplasia. CAH is an autosomal recessive disorder that affects approximately 1 in 10,000 newborns and results in deficient secretion of cortisol. Decreased cortisol synthesis leads to elevated ACTH levels, which produces adrenal hyperplasia. Five different enzyme deficiencies can cause CAH, but deficiency of 21-alpha-hydroxylase accounts for more than 90% of cases. Impaired 21-hydroxylase activity causes deficient production of cortisol and aldosterone. Depending on the extent of the enzyme deficiency, CAH may present as either a salt losing (75% of cases) or a non-salt losing disorder during the newborn period. Patients with the salt losing disorder have severe cortisol and aldosterone deficiencies that result in adrenal crisis during the second week of life. Symptoms include poor feeding, lethargy, vomiting, dehydration, hypotension and ambiguous genitalia. Laboratory findings include hyponatremia, hyperkalemia, hypocapnia and hypoglycemia. Patients with the non-salt losing form have sufficient mineralocorticoid production to avoid adrenal crisis and usually present with ambiguous genitalia.

Both types of CAH are associated with genital abnormalities because 21-hydroxylase deficiency prevents precursor hormones, such as 17-hydroxyprogesterone (17-OHP), from entering the cortisol metabolic pathway. These precursors accumulate and spill over into the androgen metabolic pathway, forming androstenedione and testosterone. Increased androgens cause masculinization of female newborns leading to ambiguous genitalia at birth and virilization later in life. In both sexes, excess androgens during childhood can result in precocious puberty, premature growth acceleration, early epiphyseal fusion, and adult short stature. CAH screening is performed by measuring levels of 17-OHP in dried blood spots.

Levels of < 50 ng/mL are considered normal for a normal weight infant of 2250 grams or greater. The reference range is adjusted higher for lower birth weight infants: <135 ng/mL for <1250 g, <90 ng/mL for 1250 to 1749 g and <65 for 1750 to 2249 g body weight. Both types of CAH produce elevated levels of 17-OHP.

The timing of blood sampling is very important in interpretation of results. In all newborn infants, 17-OHP concentrations are high on the first day of life and fall during the first week. Blood samples drawn after the second day of life allow good discrimination of 17-OHP levels between normal and affected infants.

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