Addison disease primary adrenal insufficiency

Addison Disease:
Primary adrenal insufficiency (hypocortisolism and hypoaldosteronism) is
often termed Addison disease. Addison disease is relatively rare, occurring most often in adults
30 to 60 years of age, although it may appear at any time. The most common cause of Addison
disease in the United States is autoimmune destruction of the adrenal cortex and it is more
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common in women. Other causes include infections (tuberculosis, fungal infections, human
immunodeficiency virus [HIV]), infiltrative diseases (amyloidosis, metastatic carcinoma), or
bilateral adrenal hemorrhage. Adrenoleukodystrophy and adrenomyeloneuropathy are two rare
types of X-linked adrenal deficiency that lead to symptoms of hypocortisolism and progressive
neurologic symptoms. Pathophysiology. Addison disease is characterized by inadequate
corticosteroid and mineralocorticoid synthesis and elevated serum ACTH levels (loss of negative
feedback). Before clinical manifestations of hypocortisolism are evident, more than 90% of total
adrenocortical tissue must be destroyed. Idiopathic Addison disease (organ-specific autoimmune
adrenalitis) causes adrenal atrophy and hypofunction and is an organ-specific autoimmune
disease. (Autoimmunity is discussed in Chapter 9.) It may occur in childhood (type 1) or
adulthood (type 2). 21-Hydroxylase autoantibodies and autoreactive T cells specific to adrenal
cortical cells are present in 50% to 70% of individuals with idiopathic Addison disease; this
percentage increases in younger persons and in those with other autoimmune diseases. This
deficiency allows the proliferation of immunocytes directed against specific antigens within the
adrenocortical cells. The adrenal glands in idiopathic Addison disease are smaller than normal
and may be misshapen. Several genes have been identified. Idiopathic Addison disease often is
associated with other autoimmune diseases and in such cases is known as autoimmune
polyendocrine syndrome (APS). APSI (APS type I) is inherited as autosomal recessive with
childhood onset and includes Addison disease, hypoparathyroidism, mucocutaneous candidiasis,
and other less common symptoms. APSII (APS type II) is more common and involves Addison
disease, immune thyroid disease, diabetes mellitus, celiac disease, and hypogonadism. The
symptoms of Addison disease are primarily a result of hypocortisolism and hypoaldosteronism
and are often vague and not well-defined. With mild to moderate hypocortisolism, symptoms
usually begin with weakness and easy fatigability. Skin changes, including hyperpigmentation
and vitiligo, may occur. As the condition progresses, anorexia, nausea, vomiting, and diarrhea
may develop. Symptoms of mineralocorticoid deficiency include hypovolemia, postural
hypotension and dizziness, dehydration, hyperkalemia, and salt craving. Of greatest concern is
the development of hypotension that can progress to complete vascular collapse and shock. This
is known as adrenal crisis or addisonian crisis, and develops with undiagnosed disease, acute