Autoimmune adrenalitis

Patients with autoimmune adrenal insufficiency may have other autoimmune disorders such as type 1 diabetes mel-litus and autoimmune thyroiditis. 

Addisons disease, results from progressive destruction or dysfunction of the adrenal glands by a local disease process or systemic disorder (Box 51-12), Worldwide, infectious diseases are the most common cause of primary adrenal insufficiency and include tuberculosis, fongal infections (histoplasmosis and cryptococcosis), and cytomegalovirus infections. Autoimmune adrenalitis accounts for more than 70% of cases reported in the Western world, with adrenal autoantibodies noted in more than 75% of cases,. The adrenal glands are atrophic, with loss of cortical cells but an intact medulla. Almost 50% of patients with autoimmune adrenalitis have an associated autoimmune disease with autoimmune thyroid disease the most common. 

Betterle C, Dal Pra C, Mantero F, Zanchetta R (2002) Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocrinol Rev, 23 327-364. 

REPLACEMENT THERAPY Adrenal insufficiency can result from structural or functional lesions of the adrenal cortex (primary adrenal insufficiency or Addison s disease) or from structural or functional lesions of the anterior pituitary or hypothalamus (secondary adrenal insufficiency). In developed countries, primary adrenal insufficiency most frequently is secondary to autoimmune adrenal disease, whereas tuberculous adrenalitis is the most frequent etiology in underdeveloped countries. Other causes include adrenalectomy, bilateral adrenal hemorrhage, neoplastic infiltration of the adrenal glands, acquired immunodeficiency syndrome, inherited disorders of the steroidogenic enzymes, and X-Unked adrenoleukodystrophy. Secondary adrenal insufficiency resulting from pituitary or hypothalamic dysfunction generally presents in a more insidious manner than does the primary disorder, probably because mineralocorticoid biosynthesis is preserved. 

Autoimmune—accounts for 70%-90% of all cases of primary adrenal insufficiency... 

The presence of anti-adrenal antibodies is suggestive of an autoimmune etiology. 

Named after Thomas Addison who first described the clinical condition in the mid 1850s, Addison s disease is one of the commonest endocrinopathies. At one time, most cases of Addison s were due to infection, usually by tuberculosis, of the adrenal cortex but nowadays the likely cause is autoimmune destruction of the tissue, and may be associated with dysfunction of other endocrine glands. 

Autoimmune polyglandular syndrome-Chron c autoimmune thyroiditis may occur in association with other autoimmune disorders. Treat patients with concomitant adrenal insufficiency with replacement glucocorticoids prior to initiation of treatment. Failure to do so may precipitate an acute adrenal crisis when thyroid hormone therapy is initiated. Patients with diabetes mellitus may require upward adjustments of their antidiabetic therapeutic regimens. Nontoxic diffuse goiter or nodular thyroid disease Use caution when administering levothyroxine to patients with nontoxic diffuse goiter or nodular thyroid disease in order to prevent precipitation of thyrotoxicosis. If the serum TSH is already suppressed, do not administer levothyroxine. 

Examples of some conditions which are known,or are believed to be, to be autoimmune responses include myasthenia gravis (destruction of acetylcholine receptors), rheumatic fever (a streptococcal infection challenges the immune system and then the immune system mistakes heart tissue for another strep infection), Addison s disease (destruction of the adrenal glands), arthritis (an infection of unknown origin starts the immune response but somehow IgG becomes changed, enough so as to start another IgM response - this time to the body s own IgG), pernicious anemia (inability to process vitamin B12)- insulin-dependent diabetes mellitus (IDDM or type I diabetes), multiple sclerosis, aspermatogenesis, and photosensitivity. 

Adrenal insufficiency can be associated with hypothyroidism (either by autoimmune destruction or due to hypophyseal disease) and carries the risk of acute Addisonian crisis if thyroid substitution precedes glucocorticoid therapy. The diagnostic problem presented by the fact that a few patients with central hypothyroidism have a moderately increased serum TSH should be kept in mind (62). 

Of 62 initially autoantibody-negative patients treated with interferon alfa for chronic hepatitis C for a mean of 8 months, three developed antibodies to 21b-hydroxylase, a sensitive assay of adrenocortical autoimmunity (528). However, there were no cases of Addison s disease or subclinical adrenal insufficiency. This study suggested that the adrenal cortex is another potential target organ of autoimmune effects of interferon alfa, along with thyroid and pancreatic islet cells. 

Autoimmune polyglandular syndrome with progressive thyroid autoimmunity, type 1 diabetes mellitus, amenorrhea, and adrenal insufficiency has been reported in a 51-year-old woman treated with interferon alfa for chronic hepatitis C (545). Pancreas and pituitary gland autoantibodies, which were undetectable before interferon alfa treatment, were present at the time of diagnosis. After withdrawal, she recovered normal thyroid function, but was still insulin dependent with amenorrhea and adrenal insufficiency. 

Several relatively common disorders result in aldosterone secretion abnormalities and aberrations of electrolyte status. In Addison s disease, the adrenal cortex is often destroyed through autoimmune processes. One of the effects is a lack of aldosterone secretion and decreased Na+ retention by the patient. In a typical Addison s disease patient, serum [Na+] and [CL] are 128 and 96 meq/L, respectively (see Table 16.2 for normal values). Potassium levels are elevated, 6 meq/L or higher, because the Na+ reabsorption system of the kidney, which is under aldosterone control, moves K+ into the urine just as it moves Na+ back into plasma. Thus, if more Na+ is excreted, more K+ is reabsorbed. Bicarbonate remains relatively normal. The opposite situation prevails in Cushing s disease, however, in which an overproduction of adrenocorticosteroids, especially cortisol, is present. Glucocorticoids have mild mineralocorticoid activities, but ACTH also increases aldosterone secretion. This may be caused by an oversecretion of ACTH by a tumor or by adrenal hyperplasia or tumors. Serum sodium in Cushing s disease is slightly elevated, [K+] is below normal (hypokalemia), and metabolic alkalosis is present. The patient is usually hypertensive. A more severe electrolyte abnormality is seen in Conn s syndrome or primary aldosteronism, usually caused by an adrenal tumor. Increased blood aldosterone levels result in the urinary loss of K+ and H+, retention of Na+ (hypernatremia), alkalosis, and profound hypertension. 

Tsigos C, Chrousos GP (1994) Physiology of the hypothalamic-pituitary-adrenal axis in health and dysregulation in psychiatric and autoimmune disorders. Endocrinol Metab Clin North America 23 451 166. 

DEFICIENCY In Addison s disease, there is adrenal conical insufficiency of both glucocorticoids and mineraiocorticoids. The patient may have hypotension, low serum sodium, weakness, and excess skin pigmentation. The condition may be secondary to autoimmune disease affeetiiig the adreiiul gland, or infection (e.g. Tb, AIDS). 

Autoimmune oophoritis Resistant ovary syndrome Polycystic ovary syndrome Adrenal disorders (congenital adrenal hyperplasia)... 

Premature ovarian failure (idiopathic, autoimmune, injury) Antimetabolite therapy Adrenal disorders... 

Most cases of Addison disease are a result of idiopathic atrophy of the adrenal cortex induced by autoimmune responses, although a number of other causes of adrenal cortex destruction have been described. Hypoadrenocorticism results in decreased production of cortisol and, in some... 

As described, in Addison s disease adrenal cortex function is inadequate. The most common cause of Addison s disease is the autoimmune destruction of the adrenal gland. (The major cause of adrenal insufficiency before the 1920s was tuberculosis of the adrenal gland.) Addison s disease also results from prolonged glucocorticoid therapy. (Recall that certain glucocorticoids are used as anti-inflammatory chugs.)... 

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