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Current Evidence Acute adrenal insufficiency occurs when the adrenal cortex fails to produce enough glucocorticoid and mineralocorticoid in response to stress Because the production of corticosteroids by the adrenal cortex is under pituitary and hypothalamic control, adrenal insufficiency can result from either an adrenal (primary) or hypothalamic–pituitary (secondary) disorder Specific adrenal problems resulting in adrenal insufficiency include inborn errors of hormonal biosynthesis (discussed in the Congenital Adrenal Hyperplasia section), autoimmune destructive processes, X-linked adrenoleukodystrophy, and adrenal hemorrhage Hypothalamic–pituitary causes include CNS tumors, trauma, and radiation therapy for a variety of neoplastic disorders Exogenous administration of glucocorticoids also suppresses the adrenal–pituitary axis, an effect that often lasts well beyond the cessation of corticosteroid therapy TABLE 89.5 COMMON CAUSES OF ACUTE ADRENAL INSUFFICIENCY IN CHILDREN Primary adrenal insufficiency Adrenoleukodystrophy (X-linked) Congenital adrenal hyperplasia Autoimmunity Tuberculosis Meningococcal septicemia Adrenal hemorrhage Secondary adrenal insufficiency Suppression of adrenocorticotropic hormone by pharmacologic doses of glucocorticoid administration Pituitary or hypothalamic tumors Central nervous system surgery or irradiation Structural abnormalities (septo-optic dysplasia) Congenital hypopituitarism Glucocorticoids are essential for withstanding stress; therefore, adrenal insufficiency is most likely to be manifested during an intercurrent infection or after trauma Mineralocorticoids, especially aldosterone, play an important role in salt and water homeostasis by promoting salt reabsorption in the distal renal tubules and collecting ducts Mineralocorticoid production is primarily regulated by the renin–angiotensin system; thus, adrenal insufficiency resulting from hypothalamic–pituitary causes is rarely associated with a lack of aldosterone However, aldosterone deficiency is a common feature in primary adrenal insufficiency Because of the nature of the pituitary–adrenal axis, primary adrenal insufficiency is accompanied by significantly elevated ACTH levels Clinical Considerations Clinical Recognition Adrenal insufficiency is generally recognized in patients with general fatigue associated with weight loss and abnormal electrolytes or more acutely in critically ill patients who decompensate after a minor prodrome and not respond to early interventions Triage In children with known adrenal insufficiency, early assessments should focus on vital signs and mental status Initial Assessment/H&P Children with a primary adrenal defect are more likely to have had a gradual onset of symptoms, such as general malaise, anorexia, fatigue, and weight loss Salt craving and postural hypotension may also have been noted Waterhouse–Friderichsen syndrome, or acute adrenal infarction, should be considered in a patient with fulminant sepsis and hypotension unresponsive to vasopressors or inotropes, especially if due to meningococcemia A child with secondary adrenal insufficiency is more likely to have a history of neurosurgical procedures, head trauma, CNS pathology, or chronic disease necessitating the prolonged use of glucocorticoids Findings on physical examination are more likely to be characteristic of the precipitating illness or trauma rather than specifically suggestive of adrenal insufficiency Although a lack of glucocorticoid and aldosterone can be associated with hypotension and dehydration, a better clue to the possibility of adrenal insufficiency is inappropriately rapid decompensation in the face of metabolic stress Hyperpigmentation may be present in primary adrenal insufficiency, especially of long duration Red hair and peripheral eosinophilia may be noted in Addison disease or autoimmune destruction of the adrenals Management/Diagnostic Testing Biochemical evidence suggestive of adrenal insufficiency includes hyponatremia, hyperkalemia, hypoglycemia, and hemoconcentration Metabolic acidosis and hypercalcemia may be present The definitive diagnosis depends on the demonstration of an inappropriately low level of cortisol in the serum Blood should be obtained for the measurement of both cortisol and ACTH at baseline if the diagnosis is suspected, but should not delay the administration of hydrocortisone if the patient is critically ill For stable children, cortisol measurement can be measured 60 minutes after IV or IM administration of 0.25 mg of a synthetic ACTH preparation (i.e., cosyntropin) Although ACTH dosing practice varies across institutions, we recommend using weight-based dosing (15 mCg/kg) as follows: Cosyntropin 101.3°F [38.5°C]), emesis/diarrhea, fracture, altered mental status, or shock Current Evidence Inborn errors of adrenal steroid biosynthesis are grouped under the term congenital adrenal hyperplasia (CAH) Two major modes of presentation occur in early infancy and require prompt diagnosis and treatment: acute salt-losing crisis and ambiguous genitalia ( Table 89.6 ) CAH may also present in children as precocious virilization This form of CAH warrants investigation, but it does not require emergency management The most common form of CAH presenting in infancy is 21-hydroxylase deficiency, which is recessively inherited and accounts for 90% of all cases Clinically apparent salt wasting develops in approximately two-thirds of affected patients In the United States, the incidence of 21-hydroxylase deficiency is approximately in 15,000 live births The enzymes 21-hydroxylase, 11β-hydroxylase, 3βhydroxysteroid dehydrogenase, and 20,22-desmolase are involved in the production of both cortisol and aldosterone ( Fig 89.1 and Table 89.6 ) Because the hypothalamic–pituitary axis is under feedback control by cortisol, the lack of production of this hormone caused by the enzyme deficiency results in a significant increase in ACTH In turn, ACTH stimulates the adrenal to increase steroid hormone production Because cortisol synthesis is impaired, the precursors of cortisol accumulate significantly The symptoms and signs characteristic of each enzymatic deficiency reflect either the absence of cortisol or aldosterone or the accumulation of their precursors Impairment of mineralocorticoid synthesis by 21-hydroxylase, 3β-hydroxysteroid dehydrogenase, and 20,22-desmolase deficiency can result in salt wasting Although 11βhydroxylase deficiency also blocks aldosterone production, the immediate precursor to the block, deoxycorticosterone, has potent mineralocorticoid activity Thus, instead of developing salt loss, patients with this enzyme defect often develop hypertension during childhood Androgenic compounds accumulate in 21-hydroxylase and 11β-hydroxylase deficiencies Females with these defects are virilized in utero and are born with ambiguous genitalia; therefore, females are often identified in the newborn period Some female infants are so virilized that they are mistaken as males with bilateral cryptorchidism Males have normal genital development; therefore, the diagnosis is generally missed until they present with saltwasting crisis during infancy or with evidence of precocious puberty during childhood Deficiency of 3β-hydroxysteroid dehydrogenase leads to underproduction of testosterone Boys with this deficiency are undervirilized because only weak androgens are produced, whereas girls are mildly virilized because of these weak androgens Lack of cortisol renders the patient more susceptible to hypoglycemia and reduces the tolerance to severe stress, such as dehydration Clinical Considerations Clinical Recognition CAH may manifest at birth with the discovery of ambiguous genitalia, between and weeks of age when the baby presents with acute salt-losing crisis, or during childhood with the onset of precocious puberty The affected child may come to the ED for any of these reasons Although all US states now screen newborns for CAH, the results may not be available for to weeks and the acute salt-losing crisis may occur before this time Furthermore, the report of an abnormal test result may precipitate a visit to the ED: Unless the child is ill, consultation with a pediatric endocrinologist is highly recommended before initiating therapy Salt wasting ... minute Cosyntropin ≥8.34 kg: 250 mCg IV over minute Results are unlikely to be available on an emergency basis Treatment of adrenal crisis with shock is based upon rapid volume expansion and... immediately with fluid resuscitation, glucocorticoids, and careful monitoring of electrolytes Administer emergency glucocorticoid therapy (50 mg/m2) to patients with known AI/congenital adrenal hyperplasia... children as precocious virilization This form of CAH warrants investigation, but it does not require emergency management The most common form of CAH presenting in infancy is 21-hydroxylase deficiency,