Adrenal Insufficiency

Walter L. Miller

Signs and symptoms of adrenal insufficiency are listed in Table 534-1. Most patients with chronic adrenal insufficiency have weakness, fatigue, anorexia, weight loss, hypotension, and hyper-pigmentation. Patients with acute adrenal insufficiency may have hypotension, shock, weakness, apathy, confusion, anorexia, nausea, vomiting, dehydration, abdominal or flank pain, hyperthermia, and hypoglycemia. Deficient adrenal androgen secretion will compromise the acquisition of virilizing secondary sexual characteristics (pubic and axillary hair, acne, axillary odor) in female adolescents.

Table 534-1. Signs and Symptoms of Adrenal Insufficiency

Many conditions will cause adrenal insufficiency, including congenital adrenal hyperplasia (CAD), hypopituitarism with corticotropin (ACTH) deficiency, and primary adrenal disorders. Primary adrenal insufficiency is commonly termed Addison disease; in adults, over 80% of Addison disease is due to autoimmune adrenalitis. The adrenal disorders of infants, children, and adolescents differ from those of adults and are shown in Table 534-2. Adrenal disorders are typically divided into chronic and acute causes, but many acute presentations reflect emergence of an undiagnosed underlying chronic or developmental process. Acute presentations may be triggered by intercurrent illness, trauma, or surgery, with poor fluid and sodium intake. A correct diagnosis facilitates long-term management and genetic counseling and assessing associated features.^1-3

ACUTE PRIMARY ADRENAL INSUFFICIENCY

Acute adrenal crisis commonly occurs in the child with undiagnosed chronic adrenal insufficiency at the time of additional stress (major illness, trauma, or surgery). The presenting symptoms and signs include abdominal pain, fever, hypoglycemia with seizures, weakness, apathy, nausea, vomiting, anorexia, hyponatremia, hypochloremia, acidemia, hyperkalemia, hypotension, shock, cardiovascular collapse, and death. Treatment requires fluid and electrolyte resuscitation, ample doses of glucocorticoids, chronic glucocorticoid and mineralocorticoid replacement, and treatment of the precipitating illness.

Massive adrenal hemorrhage with shock from blood loss can occur in large infants following traumatic delivery.⁴ A palpable flank mass can be distinguished from renal vein thrombosis by microscopic rather than gross hematuria; the diagnosis is confirmed by computerized tomography or ultrasonography.⁵ Massive adrenal hemorrhage may also be associated with meningococcemia (Waterhouse-Friderichsen syndrome). A similar adrenal crisis may also occur rarely with septicemia from Streptococcus, Pneumococcus, Pseudomonas, diphtheria, and methicillin-sensitive or resistant Staphylococcus.⁶

CHRONIC PRIMARY ADRENAL INSUFFICIENCY

Symptoms and signs of chronic adrenal insufficiency are shown in Table 534-1. In primary chronic adrenal insufficiency, the low concentrations of plasma cortisol stimulate the hypersecretion of ACTH, leading to hyperpigmentation, especially in skin exposed to sun and in flexor surfaces such as knees, elbows, and knuckles.

Diagnosis of adrenal insufficiency requires measurement of a low morning cortisol level with a high ACTH, confirmed by a minimal response of cortisol to a 60-minute intravenous ACTH test. Hyponatremia, hyperkalemia, low aldosterone, and elevated plasma renin activity (PRA) suggest a disturbance in mineralocorticoid production. Treatment requires physiologic glucocorticoid and mineralocorticoid replacement therapy.

Causes of primary chronic adrenal insufficiency are discussed below.

AUTOIMMUNE ADRENALITIS

Autoimmune adrenalitis is rare in children. The diagnosis of autoimmune adrenalitis is based on finding antiadrenal antibodies. About half of adult patients with autoimmune adrenalitis also have autoimmune disease of another endocrine tissue. Some of these autoimmune polyendocrine syndromes (APSs) are more prevalent in childhood.

TYPE 1 AUTOIMMUNE POLYENDOCRINE SYNDROME

APS1, or autoimmune polyendocrinopathy-candidiasis-ectodermal dysplasia (APECED), is characterized by chronic mucocutaneous candidiasis, autoimmune Addison disease, and hypoparathyroidism^7,13; at least 2 of these features must be present to make the diagnosis. The age of onset is highly variable. Chronic mucocutaneous candidiasis usually appears in early childhood and affects the mouth and nails. The hypoparathyroidism typically presents with clinical hypocalcemia during mid- or late childhood, but hypocalcemia may be masked by untreated adrenal insufficiency. The adrenal disorder usually presents in childhood or adolescence; autoimmune adrenal disease may be a presenting feature in about 5% of cases.¹³ Additional autoimmune features include alopecia and vitiligo; gastritis, chronic diarrhea, and malabsorption with or without pernicious anemia; hypergonadotropic hypogonadism (especially in women); and, less commonly, hepatitis, thyroiditis, interstitial nephritis, myositis, dental enamel hypoplasia, acquired asplenia, and type 1 diabetes mellitus. Keratoconjunctivitis is an associated feature that requires careful monitoring and treatment to prevent blindness. APS1 is common among people of Finnish (1:15,000), Sardinian, and Iranian Jewish (1:9000) ancestry.¹ APS1 is caused by recessively inherited mutations in the AIRE (for autoimmune regulator) gene.^14,15

Table 534-2. Causes of Adrenal Insufficiency

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