Autoimmune disorders, thyroid disease

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. 

Interferons are contraindicated in individuals with autoimmune hepatitis or other autoimmune disease, uncontrolled thyroid disease, severe cardiac disease, severe renal or hepatic impairment, seizure disorders, and CNS dysfunction. Immunosuppressed transplant recipients should not receive interferons. Interferons should be used with caution in persons who have myelosuppression or who are taking myelosuppressive drugs. Preparations containing benzyl alcohol are associated with neurotoxicity, organ failure, and death in neonates and infants and therefore are contraindicated in this population. Interferons should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 

Graves disease is considered to be an autoimmune disorder in which helper T lymphocytes stimulate lymphocytes to synthesize antibodies to thyroidal antigens. The antibody described previously (TSH-R Ab [stim]) is directed against the TSH receptor site in the thyroid cell membrane and has the capacity to stimulate growth and biosynthetic activity of the thyroid cell. Spontaneous remission occurs but some patients require years of antithyroid therapy. 

Possible mechanisms need to be clarified. Since thyroid autoantibodies are detected in most patients who develop thyroid disorders, the induction or exacerbation of preexisting latent thyroid autoimmunity is the most attractive hypothesis. This is in accordance with the relatively frequent occurrence of other autoantibodies or clinical autoimmune disorders in patients who develop thyroid disorders (514). However, 20-30% of patients who develop thyroid diseases have no thyroid antibodies, and it is thus not yet proven that autoimmunity is the universal or primary mechanism. In fact, there were subtle and reversible defects in the intrathyroidal organification of... 

The immunological predisposition to thyroid disorders has been studied in 17 of 439 Japanese patients who had symptomatic autoimmune thyroid disorders during interferon alfa treatment (521). There was a significantly higher incidence of the human leukocyte antigen (HLA)-A2 hap-lotype compared with the general Japanese population (88 versus 41%), suggesting that HLA-A2 is a possible additional risk factor for the development of interferon alfa-induced autoimmune thyroid disease. 

The possibility of autoimmune disorders during interferon alfa treatment has been addressed by many authors. The spectrum of interferon alfa-induced immune diseases includes organ-specific and systemic autoimmune diseases, such as thyroiditis, diabetes, hematological disorders, systemic lupus erythematosus, rheumatoid arthritis, dermatological disease, and myasthenia gravis (156). Several have been discussed in appropriate sections elsewhere in this monograph. The exact role of interferon alfa is usually difficult to ascertain, because the underlying disease, that is chronic hepatitis C, can also be associated with immune-mediated disease. 

Hyperthyroidism results in a hypermetabolic state due to an excess of thyroid hormones. Hyperthyroidism is more common in women (2%) than men (0.1%). Graves disease is an autoimmune disorder that leads to hyperthyroidism, diffuse goiter, ophthalmopathy, dermopathy, and acropachy. Graves disease is the most common cause of hyperthyroidism, more common than multi- or uninodular goiters. 

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. 

Thyrotoxicosis is most commonly caused by Graves disease, which is an autoimmune disorder in which thyroid-stimulating antibody (TSAb) directed against the thyrotropin receptor elicits the same biologic response as thyroid-stimulating hormone (TSH). 

Graves disease An autoimmune disorder in which antibodies overstimulate the production of thyroid hormones leading to a condition of hyperthyroidism, or elevated thyroid hormone synthesis and secretion. 

In developed countries, where iodine deficiency is rare because of the use of iodized salt, autoimmune disorders are a leading cause of thyroid disease. 

The least well characterized autoimmune polyglandular syndrome is the type 3 syndrome. This syndrome is defined by the presence of autoimmune thyroid disease with another autoimmune disease, such as diabetes mellitus type l, autoimmune gastritis, or myasthenia gravis, but in the absence of Addison disease. APGS type 3 primarily involves females (the female to male ratio is 7 1) who have HLA-DR3-associated autoimmune disease and is probably the most common of the autoimmune polyglandular syndrome disorders. Since different and multiple clinical combinations can be found, the classification of this type of autoimmune polyglandular syndrome is probably more complicated than originally anticipated. 

Strieder TGH, Prummel MF, Tijssen JGP, Ended E, Wiersinga WM (2003) Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease. Clin Endocrinol, 59 396-401. 

One of the first retrospective epidemiologic studies of teenage children demonstrated an association of soy consumption in early infancy and a higher prevalence of autoimmune thyroid diseases (Fort et al., 1990). This work was criticized, in part because children were often fed with soy formulas in order to prevent allergic disorders, known to be associated with autoimmune diseases (Chandra, 1997). 

AITD have high concentrations of circulating thyroid autoantibodies (Arai et ai, 2000 Carle et aL, 2006 Feldt-Rasmussen, 1996), for the most part the disorder appears to be the consequence of tissue damage initiated by T lymphocytes (Weetman and McGregor, 1994). Measurement of autoantibodies against thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) has for many years been a major tool in the diagnosis of autoimmune thyroid diseases, such as Hashimotos thyroiditis, primary myxedema and postpartum thyroiditis (Feldt-Rasmussen et ai, 1991 Feldt-Rasmussen, 1996). 

In autoimmune thyroid diseases, a marked gender difference in prevalence is reported with a 5- to 10-fold excess in females (Manji et al., 2006 Rendl and Sailer, 2001). A significant family clustering of Graves disease or Hashimoto s thyroiditis was observed in 40—50% of patients, who reported another family member with thyroid disorders (Manji et al., 2006). 

Hashimoto s disease, named after the physician who first described it. Is an autoimmune disorder in which plasma cells, lymphocytes, and fibrous tissue attack and destroy the thyroid gland. Pitt-Rivers and Tata (57) suggested that the sequence of events in Hashimoto s disease was initiated by injury to some thyroid structure, following which the normally sequestered thyroglobulin would be released and exposed to immunological mechanisms, thus setting into motion a progressive interaction between ... 

Dysthyroid endocrine orbitopathy (EO) or thyroid eye disease is the most common disorder affecting the orbit, usually presents in middle-aged women, and represents the most frequent cause of unilateral or bilateral proptosis in adults (Mueller-Forell and Pitz 2004 Aviv and Miszkiel 2005). EO is predominantly associated with autoimmune hyperthyroidism, which is also referred to as Morbus Basedow or Grave s disease (Mueller-Forell and Pitz 2004), but the orbitopathy may precede thyroid disease or occur with euthyroid or hypothyroidism (Aviv and Miszkiel 2005). EO is associated with edema of all structures of the orbit. The hallmarks of EO, however, are spindle-shaped edema of the intra-orbital muscles, which leaves out the tendons, and enlargement of the intra-orbital fat tissue (Fig. 12.7) (Mueller-Forell and Pitz 2004 Aviv and Miszkiel 2005). Muscular edema usually is most pronounced in... 

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