Endocrine Gland Disorders: Thyroid Disease
المؤلف:
Mary Louise Turgeon
المصدر:
Immunology & Serology in Laboratory Medicine
الجزء والصفحة:
5th E, P387-389
2025-09-22
126
Numerous endocrine gland disorders are attributable to an autoimmune process. Several of the classic and more common disorders are discussed in this section.
The clinical spectrum of autoimmune thyroid disease is very broad. There are two major forms of autoimmune thyroid dis ease, chronic autoimmune thyroiditis and Graves’ disease.
Lymphoid (Hashimoto’s) chronic thyroiditis is a classic example of an organ-specific autoimmune disorder. Other autoimmune disorders affecting the thyroid gland include transient thyroiditis syndrome and idiopathic hypothyroidism.
Lymphoid (Hashimoto’s) Chronic Thyroiditis
Etiology. The exact causative mechanism is unknown but is believed to be related to an autoimmune process in which the development of circulating cytotoxic antibodies eventually destroys the thyroid gland, producing hypothyroidism. This disorder is associated with the presence of human leukocyte antigen (HLA)–DR4 and HLA-DR5. However, these associations are not consistent in different races and ethnic groups.
Epidemiology. Lymphoid thyroiditis can occur at any age but is first diagnosed most often in the third to fifth decades of life; it is much more common in women than in men. The fibrous variant of the disease is more often present in middle-aged and older patients.
The mode of inheritance is unknown. However, a genetic tendency to inherit the trait for the development of antibodies against the thyroid gland is highly possible. It is common to have multiple members of a family develop the same disease (e.g., Graves’ disease, lymphoid thyroiditis).
Signs and Symptoms. Lymphoid thyroiditis is believed to be the most common cause of sporadic goiter. Characteristically, there is a firm, diffusely enlarged, nontender thyroid gland that may be lobulated. Hypothyroidism, however, is a common late sequela of lymphoid thyroiditis, and patients are usually euthyroid when first seen by a physician. Some individuals have clinical and pathologic evidence of the coexistence of Graves’ disease and lymphoid (Hashimoto’s) thyroiditis. Histologically, Hashimoto’s thyroiditis is characterized by diffuse lymphocytic infiltration (Fig. 1).
Fig1. Comparison of histologic architecture of the thyroid gland of normal patient, and patient with Hashimoto’s disease. A, In the normal thyroid, colloid fills the vesicles, but in a diseased gland (B), only isolated deposits of colloid are seen. The cell infiltrate is lymphoid in nature. Note germinal center in lower middle (B). (From Anderson JR, Buchanan WW, Goudie RB: Autoimmunity, Springfield, Ill, 1967, Charles C Thomas.)
Immunologic Manifestations
Patients with lymphoid thyroiditis, as well as other autoimmune thyroid disorders, can demonstrate histologic and immunologic manifestations of the disease. Antibodies to thyroid constituents may be observed in these patients. Antibodies to the following constituents may be demonstrated serologically:
• Thyroglobulin
• Thyroid microsome
• Second colloid antigen (CA2 antigen)
• Thyroid membrane receptors
• Thyronine (T4) and triiodothyronine (T3)
Thyroglobulin. Antithyroglobulin (TgAb) was the first antibody discovered against a thyroid protein, thyroglobulin. Immunofluorescent laboratory methods using fluorescein-labeled anti–human globulin can demonstrate the binding of antithyroglobulin anti body to thin sections of thyroid tissue in abnormal conditions or in approximately 4% of the normal population. The frequency of positive titers gradually increases in the female population with aging. The absence of antithyroglobulin antibodies, however, does not exclude the diagnosis of Hashimoto’s thyroiditis; conversely, the presence of antibodies does not establish the diagnosis because it can be positive in Graves’ disease and is occasionally positive in thyroid cancer and subacute thyroiditis. Testing for antibody may also be used to monitor patients with thyroid cancers.
Thyroid Microsomes. Antibodies directed against thyroid microsomes, antithyroid microsomal antibodies, or antithyroperoxidase antibodies (TPO Abs) can be detected in about 7% of the population, with titers ranging from 1:100 to 1:1600. Even a low titer of antithyroid antibodies correlates with a degree of thyroid involvement by an autoimmune process. The absence of antibodies has been documented in diagnosed cases of autoimmune thyroiditis, which may be explained by special characteristics of the antibody, or because it forms complexes with thyroglobulins in the circulation and escapes detection. The presence of these circulating complexes has been documented in patients with thyroid autoimmune disorders.
Second Colloid Antigen. CA2 antigen is directed against a colloid protein and can be detected by immunofluorescent examination. Antibody to CA2 is present in about 50% of patients who have subacute thyroiditis, and it is detectable in some patients with Hashimoto’s thyroiditis whose sera show no other evidence of abnormal antibodies.
Thyroid Membrane Receptors. The thyroid membrane receptors are a group of immunoglobulin G (IgG) antibodies that interact with receptors on thyroid membranes. They often produce hyperthyroidism that manifests itself clinically, chemically, and histologically. At present, classification of these IgG antibodies is operational, based on their method of detection. Long-acting thyroid stimulator (LATS) and long-acting thyroid stimulator protector (LATS-P) assays are of importance.
Thyronine and Triiodothyronine. Antibodies to T4 and T3 have been found in several patients, most of whom had evidence of a thyroid autoimmune process such as goiter or hypothyroidism. In these cases, the underlying autoimmune process is most likely responsible for the hypothyroidism rather than hormone binding by the circulating antithyronine antibodies.
Diagnostic Evaluation
Fine-needle aspiration biopsy of the thyroid is useful in con junction with clinical evaluation and serologic studies for the diagnosis of lymphocytic thyroiditis.
Histologic examination of thyroid tissue demonstrates variable infiltration of the entire gland with lymphocytes. Germinal lymphoid centers are characteristic and destruction and distortion of normal thyroid follicles are apparent. The thyroid cells remain intact but are hypertrophied, although the usual heterogeneity of small, enlarged thyroid follicles, some containing flat epithelium, can also be seen. In advanced cases, there is almost complete destruction of normal thyroid tissue, with replacement by lymphocytes or fibrous tissue.
When the disease produces hypothyroidism, a slight increase in plasma thyroid-stimulating hormone (TSH) con centration can usually be demonstrated in the early phase, followed by a decrease in serum T4 and eventually by a decrease in serum T3 levels. Antithyroglobulin and/or antithyroid microsomal antibodies are found in moderate to high titers in more than 50% of patients, but the presence of antimicrosomal antibodies is considered to be more diagnostic.
Antibodies directed against thyroid microsomal antigen (thy roid peroxidase antibody [anti-TPO]) can be detected by various techniques (Table 1). Chemiluminescent immunoassay is typically performed to detect anti-TPO autoantibodies. TPO plays a significant role in the biosynthesis of thyroid hormones by catalyzing the iodination of tyrosyl residues in thyroglobulin and the coupling of iodotyrosyl residues to form T4 and T3. Autoantibodies produced against TPO are capable of inhibiting enzyme activity. They are also complement-fixing antibodies that can induce cytotoxic changes in cells and consequently cause thyroid dysfunction. More than 90% of patients with autoimmune thyroiditis (Hashimoto’s thyroiditis) have anti-TPO. Antibodies to TPO have also been found in most patients with idiopathic hypothyroidism (85%) and Graves’ disease (50%).
Table1. Antithyroid Antibody Tests
Graves’ Disease
Graves’ disease is a form of hyperthyroidism. This disease is most likely if a patient has signs and symptoms of hyperthyroidism. Laboratory chemistry assays usually demonstrate low TSH and elevated free T4 levels. Of patients with Graves’ dis ease, 50% exhibit thyroid peroxidase antibody (anti-TPO). TSH receptor antibody (TRAb) can discriminate between Graves’ disease and toxic nodular goiter. In addition, thyroid stimulating immunoglobulin can detect thyroid antibodies for diagnosing Graves’ disease.
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