Pediatric emergency medicine trisk 471

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 do 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 <4.17 kg: 62.5 mCg IV over 1 minute
Cosyntropin 4.17 to 8.34 kg: 125 mCg IV over 1 minute
Cosyntropin ≥8.34 kg: 250 mCg IV over 1 minute
Results are unlikely to be available on an emergency basis.
Treatment of adrenal crisis with shock is based upon rapid volume expansion and the
administration of glucocorticoids. Immediate management consists of 50 to 100 mg/m2 of


hydrocortisone intravenously. In the absence of a body surface area calculation, hydrocortisone
can be given as 1 to 2 mg/kg in critical illness. Subsequent management is hydrocortisone 50
mg/m2/24 hrs given intravenously continuously or divided every 6 hours. Volume expansion is
accomplished with normal saline (20 to 60 mL/kg) in the first hour, followed by fluids
appropriate for maintenance and replacement. Additional Na+ may be needed in primary
adrenal insufficiency because of ongoing urinary Na+ losses. These fluids should contain 10%
dextrose and should not contain potassium until the serum potassium is within the normal
range.
Mineralocorticoid therapy is rarely important in the acute phase, provided fluid therapy is
adequate; however, patients with primary adrenal insufficiency may need replacement with a

mineralocorticoid for long-term management. Hydrocortisone acts at the mineralocorticoid
receptor when dosed at stress levels of 50 mg/m2/day. Subsequent long-term therapy can be
accomplished with fludrocortisone. Specific therapy directed toward correction of the
hyperkalemia is rarely required unless cardiac ECG changes (peaked T wave, prolonged QRS
duration) or arrhythmias are present. Hypoglycemia is remedied by the use of dextrose and by
the hyperglycemic effects of glucocorticoids. The precipitating factor, such as infection, also
requires appropriate therapy.
Improvement in peripheral circulation and blood pressure should occur quickly with
therapy. Dramatic improvement often occurs in all parameters within hours after the first dose
of glucocorticoid. Because adrenal crisis is commonly brought on by another stress such as
infection, the symptoms of malaise, anorexia, and lethargy may take longer to resolve.
Clinical Indications for Discharge or Admission
Once instituted, high-dose glucocorticoid therapy should be continued for 48 hours, and
adequate hydration should be maintained either orally or intravenously. The patient known to
be at risk for adrenal insufficiency should wear an identifying bracelet to alert ED personnel to
this possibility.

CONGENITAL ADRENAL HYPERPLASIA
Goal of Treatment
To rapidly initiate treatment for acute salt-wasting crisis and adrenal insufficiency.
CLINICAL PEARLS AND PITFALLS
ED presentations include ambiguous genitalia, acute salt-wasting crisis, and
precocious puberty.
Patients with acute salt-wasting crisis must be recognized and treated 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 (CAH) with fever (T >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 1 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 2 and 5 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 2 to
3 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