Chronic autoimmune thyroiditis

The vast majority of hypothyroid patients have thyroid gland failure (primary hypothyroidism). The causes include chronic autoimmune thyroiditis (Hashimoto s disease), iatrogenic hypothyroidism, iodine deficiency, enzyme defects, thyroid hypoplasia, and goitrogens. 

Hypothyroidism, known as myxedema in adults, when severe, is the most common disorder of the thyroid gland. Worldwide, hypothyroidism is most often the result of endemic iodine deficiency. In nonendemic areas, where iodine is sufficient in the diet, chronic autoimmune thyroiditis (Hashimoto s thyroiditis) accounts for the majority of cases. This disorder is primarily characterized by high levels of circulating antibodies against a key enzyme (thyroid peroxidase) in the processing of iodine in the thyroid gland. Blocking antibodies directed at the TSH receptor may also be present. Thyroid destruction may also occur via apoptotic cell death. 

Two studies have provided insights into the incidence and risk factors of the immune-mediated comphcations of interferon alfa in patients with chronic myeloid leukemia. In the first study, 13 of 46 patients had autoimmune manifestations consisting of a combination of autoimmune thyroiditis in four, a direct antiglobulin test without hemolysis in eight, cryoagglutinins in one, Raynaud s phenomenon in two, and chronic autoimmune hepatitis in one (343). Overall, six patients had chnically symptomatic manifestations after a median of 15 months of treatment. In the second study, there were autoimmune diseases in seven of 76 patients after a median of 19 months of treatment, including hypothyroidism in one, immune-mediated hemolysis in two, systemic lupus erythematosus in two, Raynaud s phenomenon in one, and mixed connective tissue disease in one (344). In... 

Thyroid Hypofunction Hypothyroidism is the most common disorder of thyroid function. It can be divided into patients who have a failure of the thyroid gland to produce sufficient thyroid hormone (primary hypothyroidism) and patients in which pituitary or hypothalamic disease is associated with impaired TSH stimulation (central or secondary hypothyroidism). Worldwide, primary hypothyroidism is caused most often by iodine deficiency. In areas where iodine is sufficient, chronic autoimmune thyroiditis (Hashimoto s thyroiditis) accounts for most cases. Other causes include postpartum thyroiditis, surgical removal, or radioactive iodine ablation of the gland. Hypothyroidism present at birth (cretinism) is the most common preventable cause of mental retardation in the world. 

Reported in elderly subjects with and without possible defective organification and autoimmune thyroiditis Chronic nonthyroidal illness Cystic fibrosis... 

The occurrence of thyroid dysfunction in 72 patients treated with interferon alfa plus ribavirin (1.0-1.2 g/day) has been compared with that of 75 age- and sex-matched patients treated with interferon alfa alone for chronic hepatitis C (523). Of the former, 42 patients, and of the latter, 40 patients had received previous treatment with interferon alfa alone. There was no difference in the rate of thyroid autoimmunity (antithyroglobulin, antithyroid peroxidase, and thyroid-stimulating hormone receptor... 

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. 

Preziati D, La Rosa L, Covini G, Marcelli R, Rescalli S, Persani L, Del Ninno E, Meroni PL, Colombo M, Beck-Peccoz P. Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha-2a. Eur J Endocrinol 1995 132(5) 587-93. 

Marazuela M, Garcia-Buey L, Gonzalez-Fernandez B, Garcia-Monzon C, Arranz A, Borque MJ, Moreno-Otero R. Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-alpha 527. therapy. Clin Endocrinol (Oxf) 1996 44(6) 635-42. 

Kakizaki S, Takagi H, Murakami M, Takayama H, Mori M. HLA antigens in patients with interferon-alpha-induced autoimmune thyroid disorders in chronic hepatitis C. J Hepatol 1999 30(5) 794-800. 

Autoimmune urticaria. This seems to be an underlying basis of many cases of chronic idiopathic urticaria. About one third of patients with chronic urticaria spontaneously develop auto-antibodies directed at the receptor FceRI, located on skin mast cells. Chronic stimulation of this receptor leads to chronic hives. Patients often have other autoimmune conditions, such as autoimmune thyroiditis. 

Bystander activation activation of autoreactive cells through nonspecific inflammation and induction of inflammatory cytokines and chemokines is also of pathological consequence in MS. It has been suggested that bystander activation, induced by persistent virus infection or primed by molecular mimicry may activate autoreactive T-cells specific for the CNS (McCoy et al., 2006). Einally, cryptic antigens may also play a role in immune activation. In other immune-mediated diseases such as Chronic Lymphocytic Thyroiditis and Chagas Heart Disease, exposure of cryptic epitopes leads to the activation of autoimmune cells and further contributes to... 

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 (168). 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 intrathjroidal organification of iodine in 22% of antithyroid antibody-negative patients treated with interferon alfa (169). In addition, the acute systemic administration of interferon alfa in volunteers or chronic hepatitis patients reduces TSH concentrations (SED-13,1093) (170), and in vitro studies have suggested that interferon alfa directly inhibits thyrocyte function (SED-13, 1093) (171). Finally, the thyroid autoantibody... 

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. 

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