is present shortly after birth, but acute crisis usually does not occur until the second week of life TABLE 89.6 CLINICAL AND LABORATORY FEATURES OF VARIOUS FORMS OF CONGENITAL ADRENAL HYPERPLASIA FIGURE 89.1 Adrenal steroid hormone biosynthesis The pathways for the synthesis of adrenal steroid hormones (adrenal cortex) and catecholamines (adrenal medulla) are arranged from left to right Synthesis of all compounds originates from cholesterol in the mitochondria of the adrenal cortex Subsequent conversions are shown with enzyme names located next to open arrows , and gray lines indicating enzymatic blocks in the various forms of congenital adrenal hyperplasia (CAH) Mineralocorticoids (aldosterone) are produced in the zona glomerulosa, glucocorticoids (cortisol) in the zona fasciculata, and androgens (testosterone) and estrogens (estradiol) in the zona reticularis Cortically produced cortisol is required for full induction of the medullary conversion of norepinephrine to epinephrine (Courtesy of Joseph Majzoub, MD, Children’s Hospital Boston.) Triage Consider CAH as etiology of ill-appearing neonate; recognize importance of quickly visualizing genitalia and obtaining point-of-care blood glucose Initial Assessment/H&P The appearance of symptoms of salt-wasting crisis can be insidious, with a history of poor feeding, lack of weight gain, lethargy, irritability, and vomiting The nonspecific symptoms may lead to consideration of diagnoses other than CAH and delay initiation of treatment Examination of the child should include the vital signs and an assessment of the degree of dehydration In severe cases, there may be shock and metabolic acidosis The genitalia should be examined carefully because the degree of ambiguity of the genitalia varies considerably Virilized females may have an enlarged clitoris and fusion of the labial folds An undervirilized male may have a small phallus and/or hypospadias The presence of gonads in the inguinal canals or labioscrotal fold is suggestive of a male karyotype Hyperpigmentation of the labioscrotal folds and the nipples is occasionally present in the neonatal period; however, it is rarely prominent enough to alert the examiner to the possibility of CAH Management/Diagnostic Testing In the ED, the most urgent investigations are plasma electrolytes and blood glucose The combination of hyperkalemia and hyponatremia is often the first clue to the diagnosis of CAH, especially in males The plasma potassium is elevated, but in the presence of vomiting and diarrhea, the rise may be blunted Potassium levels between and 12 mEq/L are occasionally encountered, and can paradoxically be seen without any clinical cardiac dysfunction or ECG changes The plasma bicarbonate level is usually low, reflecting the metabolic acidosis that results from the retention of hydrogen ions in exchange for sodium loss The blood glucose is usually normal; however, hypoglycemia may occur secondary to the lack of cortisol and the reduced caloric intake during the acute illness Serum should be drawn for determination of an adrenal steroid profile to include cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, and if possible, ACTH Ideally, blood should be obtained for these tests before the administration of hydrocortisone For the child in crisis, the diagnosis must be based on physical findings and electrolyte abnormalities, and treatment must be instituted before the definitive results of the adrenal steroid profile are available Emergency glucocorticoid therapy, delivered at the stress dose of hydrocortisone 50 mg/m2/day should be administered to any patient with known CAH or other form of adrenal insufficiency in the setting of temperature above 38.5°C, emesis and/or diarrhea, bony fracture of any type, or in the setting of altered mental status or shock If the patient appears ill, an initial dose of hydrocortisone 50 mg/m2 may be given either intramuscularly or intravenously, followed by that dose divided in four and given every hours If the patient is not illappearing and is tolerating oral fluids and medications, their usual daily dose may be tripled and given in three equal parts daily, or hydrocortisone 50 mg/m2/day may be given orally in three equal parts daily if the home dose cannot be readily established Correction of Hyperkalemia, Hypoglycemia, and Acidosis Infants with CAH tolerate hyperkalemia far better than older children and adults, with potassium levels as high as 12 mEq/L reported without clinical signs Volume restoration with normal saline is the major and, usually, the only measure needed to lower the potassium In the presence of arrhythmias, IV 10% calcium gluconate mL/kg can be given for its membrane-stabilizing properties Therapy with glucose and insulin is contraindicated because of the danger of precipitating hypoglycemia If hypoglycemia is found at the time of presentation, it should be treated acutely by the administration of dextrose (0.25 g/kg) intravenously and by the subsequent inclusion of 10% dextrose in the infusate Acidosis generally does not require specific treatment; however, the low serum bicarbonate may take days to fully correct Bicarbonate therapy is reserved for patients with both severe acidosis (pH