Acute Adrenal Insufficiency
EPIDEMIOLOGY
The exact incidence of acute adrenal insufficiency in the neonate is unknown but likely mirrors the incidence of the underlying causes of the adrenal failure. Newborn screening and heightened awareness have resulted in earlier diagnosis of congenital adrenal hyperplasia (CAH) before an acute crisis develops. The incidence of adrenal suppression from pharmacological doses of steroids is likely underestimated, and the exact frequency of adrenal crises in these cases is not known.
PATHOPHYSIOLOGY AND PRESENTATION
An essential component of the normal stress response is the adrenal gland. Cortisol production is increased during stress to maintain hemodynamic stability and glucose homeostasis. In these instances, cortisol prevents hypotension by promoting water and sodium retention, increasing angiotensinogen synthesis in the liver, increasing the vascular reactivity to vasoconstrictors, promoting the enzymatic conversion of norepinephrine to epinephrine, decreasing capillary permeability, and decreasing nitric oxide and other vasodilatory mediators.1 Cortisol also prevents hypoglycemia by decreasing glucose uptake in the muscle, promoting catabolism of protein and muscle to produce substrates for gluconeogenesis, and increasing expression of gluconeogenic enzymes.1 Aldosterone is the primary mineralocorticoid produced in the adrenal cortex and exerts effects on the kidney by stimulating reabsorption of sodium and secretion of potassium and hydrogen ions. If an inadequate cortisol response occurs in the face of physiologic stress, the infant will develop an acute adrenal crisis.
Central Adrenal Insufficiency
In infants with central adrenal failure, ACTH (corticotropin) is deficient. ACTH primarily regulates glucocorticoid production and secretion. The renin-aldosterone system is controlled by systemic volume and blood pressure and is unaffected in cases of central adrenal failure; thus, the neonate will not have the severe hyperkalemia or hyponatremia that accompanies mineralocorticoid deficiency. The infant will still be at risk for hypotension, milder hyponatremia, and hypoglycemia.
Primary Adrenal Insufficiency
The adrenal cortex is affected in primary adrenal insufficiency; thus, the neonate may have both cortisol and mineralocorticoid deficiency. These infants are at risk for a salt-wasting adrenal crisis consisting of marked hyperkalemia, hyponatremia, dehydration, and hypotension.
Acute Adrenal Failure or Crisis
In the neonate, adrenal failure can result in complete circulatory collapse and metabolic dysregulation termed an adrenal crisis. Other clinical features of acute adrenal failure include severe hyperkalemia and hyponatremia and hypoglycemia, including seizure, hypotension, dehydration, prolonged jaundice, fever, vomiting, and acidosis (Table 104–1). Left untreated, the crisis will progress to shock and death.
Table 104-1 Clinical Features of Acute Adrenal Failure
Hypoglycemia
Hyponatremia
Hyperkalemia
Hypotension
Circulatory failure
Apnea
Fever
Vomiting
Jaundice/hyperbilirubinemia
Acidosis
DIFFERENTIAL DIAGNOSIS
Any form of adrenal insufficiency, whether from primary or central causes (Table 104-2), can present as acute adrenal failure or crisis. Transient forms of adrenal insufficiency may also present acutely. An infant who has been exposed to prolonged courses of steroids is at risk for the development of an adrenal crisis. In these cases, suppression of the hypothalamic-pituitary-adrenal (HPA) axis from exogenous steroids may take several weeks to months to resolve, and if the infant develops an intercurrent illness or undergoes surgery, the infant may not be able to mount the appropriate stress response.2 In addition, infants exposed to steroids in utero may also have suppression of the HPA axis postnatally. The degree and duration of suppression appear to be related to the dose and duration of antecedent steroid exposure.2,3 Adrenal hemorrhage in a large infant after traumatic deliveries can present with acute adrenal failure and cardiodynamic instability from blood loss. Infants with known adrenal insufficiency can develop an adrenal crisis if subjected to additional severe stress such as major illness or surgery.4
Table 104-2 Differential Diagnosis of Adrenal Failure
