The adrenal cortex produces two main hormones: glucocorticoid (cortisol), mineralocorticoid (aldosterone), and in addition, adrenal androgens. Acute adrenal insufficiency (AI) results from deficiency of glucocorticoids (cortisol) and mineralocorticoids (aldosterone) secreted by the adrenal cortex.

AI is classified into primary (adrenocortical failure), secondary (pituitary), or tertiary (hypothalamic) types. AI, due to withdrawal from exogenous steroid administration, is the most common cause of adrenal crisis. In infants, a common cause of primary AI is congenital adrenal hyperplasia (CAH).

Acquired AI results from autoimmune, infectious, infiltrative, hemorrhagic, or toxic causes.

Glucocorticoid deficiency impairs gluconeogenesis and glycogenolysis, and decreases the sensitivity of the vascular system to angiotensin II and norepinephrine, resulting in hypoglycemia, tachycardia, and mild hypotension. Aldosterone deficiency causes decreased sodium retention by the kidney, osmotic diuresis, hyponatremia, hypovolemia, and dehydration. In addition, it causes a decreased distal renal tubular exchange of potassium and hydrogen ions for sodium ions, leading to hyperkalemia and acidosis. Androgen deficiency in primary AI leads to underdeveloped secondary sexual characteristics in prepubertal children. In addition, in primary AI, the lack of negative feedback from cortisol on the anterior pituitary causes oversecretion of adrenocorticotropic hormone (ACTH) and propiomelanocortin that in turn stimulate skin hyperpigmentation (Fig. 78-1).

ETIOLOGY AND EPIDEMIOLOGY

One of the most common causes of AI in North America is the abrupt withdrawal of glucocorticoids while on prolonged or chronic treatment.¹ Children who have been on glucocorticoid therapy for 2 to 4 weeks or longer tend to have prolonged suppression of the hypothalamo—pituitary axis, leading to transient secondary AI after treatment is stopped.² The most common cause of primary AI in infants is CAH, with an incidence of 1 in 10,000 to 18,000 live births.³ In long-term studies of children with AI, most have primary AI, and of these, approximately 72% are found to have CAH.^4,5

CAH results from a deficiency in the enzymatic activity of one of the enzymes in the cortisol biosynthetic pathway, the most common being 21-hydroxylase deficiency. Mortality for CAH is five times that of the general population. This has improved with the present recommendation for universal screening of newborns.^6,7 Other rarer forms of congenital primary AI are congenital adrenal hypoplasia, adrenal aplasia or hemorrhage associated with a traumatic delivery,⁸ familial isolated glucocorticoid deficiency, adrenoleukodystrophy (ALD), and the “triple A syndrome,” AI, alacrima, and achalasia of the esophagus (Table 78-1).