Table 20.7 . Individuals with chronic adrenocortical insufficiency may develop an acute crisis after any stress that taxes their limited physiologic reserves. In patients maintained on exogenous corticosteroids, rapid withdrawal of steroids or failure to increase steroid doses in response to an acute stress may precipitate a similar adrenal crisis, because of the inability of the atrophic adrenals to produce glucocorticoid hormones. Massive adrenal hemorrhage may destroy enough of the adrenal cortex to cause acute adrenocortical insufficiency. This condition may occur in patients maintained on anti-coagulant therapy, in postoperative patients who develop disseminated intravascular coagulation, during pregnancy, and in patients suffering from overwhelming sepsis; in the latter setting, it is known as the Waterhouse-Friderichsen syndrome (
Fig. 20.40 ). This catastrophic syndrome is classically associated with Neisseria meningitidis septicemia but can also be caused by other organisms. Waterhouse-Friderichsen syndrome can occur at any age but is somewhat more common in children. The basis for the adrenal hemorrhage is uncertain but may be attributable to direct bacterial seeding of small vessels in the adrenal, the development of disseminated intravascular coagulation (Chapter 4), endotoxin-induced vasculitis, or some form of hypersensitivity vasculitis.
ChronicAdrenocorticalInsufficiency:AddisonDisease
Addison disease, or chronic adrenocortical insufficiency, is an uncommon disorder resulting from progressive destruction of the adrenal cortex. More than 90% of all cases are attributable to one of four disorders: autoimmune adrenalitis, tuberculosis, the acquired immune deficiency syndrome (AIDS), or metastatic cancer (see
Table 20.7 • Autoimmune adrenalitis accounts for 60% to 70% of cases and is by far the most common cause of primary adrenal insufficiency in countries where infectious causes are uncommon. As the name implies, there is autoimmune destruction of steroid-producing cells, and autoantibodies to several key steroidogenic enzymes have been detected in affected patients. Autoimmune adrenalitis may occur in association with several distinct autoimmune polyendocrine syndromes (APS). The best characterized of these is APS1, which is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome http://ebooksmedicine.net
Fig.20.40Waterhouse-Friderichsensyndrome.Bilateraladrenalhemor-rhageinaninfantwithoverwhelmingsepsis,resultinginacuteadrenalinsuf-ficiency.Atautopsy,theadrenalglandsweregrosslyhemorrhagicandshrunken;inthisphotomicrograph,littleresidualcorticalarchitectureisdiscernible.
21. It is characterized by mucocutaneous candidiasis and abnormalities of skin, dental enamel, and nails (ectodermal dystrophy) occurring in association with a combination of organ-specific autoimmune disorders that result in destruction of target organs. The AIRE protein is involved in the expression of tissue antigens in the thymus and the elimination of T cells specific for these antigens (Chapter 5). Individuals with APS1 develop autoantibodies against IL-17 and IL-22, which are the principal effector cytokines secreted by TH17 T cells (Chapter 5). Because these two TH17-derived cytokines are crucial for defense against fungal infections, affected patients develop chronic mucocutaneous candidiasis.