60: Autoimmune Thyroid Diseases

Key Points

  • Disease summary:

    • Autoimmune thyroid disorders (AITDs) include Graves disease (GD) and Hashimoto thyroiditis (HT). Both are complex genetic diseases caused by the interplay of several genes with environmental triggers (eg, infection) resulting in disruption of normal thyroid function. AITDs are some of the most common autoimmune disorders and can be associated with other autoimmune diseases. Both are found in a higher prevalence among women with the age of onset most frequently between 30 and 50 years.

    • Graves disease: Production of thyrotropin (TSH) receptor stimulating antibodies (TRAb) results in overstimulation of the thyroid gland that causes an excessive production and inappropriate release of thyroid hormones resulting in clinical hyperthyroidism, as well as thyroid enlargement (goiter) due to hypertrophy and hyperplasia of thyroid follicles.

      • Symptoms are related to hyperthyroidism, as well as those that are specific to GD: Graves ophthalmopathy (GO) and Graves dermopathy.

    • Hashimoto disease: Also known as chronic lymphocytic thyroiditis, is the most common cause of hypothyroidism in the industrialized world with a higher prevalence in iodine sufficient areas and among smokers. It is characterized by lymphocytic infiltration of thyroid gland, causing thyroid cell death and resultant hypothyroidism.

      • Symptoms are related to the lack of thyroid hormones (hypothyroidism).

  • Differential diagnosis:

    • GD: Subacute thyroiditis, postpartum thyroiditis, silent thyroiditis, toxic multinodular goiter, toxic adenoma, surreptitious ingestion of thyroid hormones, drug-induced thyroiditis (eg, amiodarone, interferon)

    • HT: Primary myxedema, postpartum thyroiditis, drug-induced hypothyroidism (eg, amiodarone, interferon, lithium)

  • Family history:

    • Familial predisposition to the development of AITD is very common. Several studies have reported a higher frequency of thyroid abnormalities in relatives of patients with AITD, most commonly the presence of thyroid antibodies.

  • Twin studies:

    • It has been reported in several studies that the concordance rate in monozygotic twins is significantly higher than in dizygotic twins, both in GD and in HT. These findings support the notion that there is a clear inherited susceptibility in AITD.

  • Environmental factors:

    • Iodine, infection, smoking, pregnancy, medications

  • Genome-wide associations:

    • There are no genome-wide association studies (GWAS) reported to date. However, several genome-wide linkage and candidate gene studies have been reported. These studies identified several non-MHC susceptibility genes including CTLA4, CD40, PTPN22, thyroglobulin, and TSHR. In addition, the presence of arginine at position 74 of the HLA-DR beta chain was strongly associated with both GD and HT.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria for AITD

Graves Disease

Diagnosis is based on the presence of primary hyperthyroidism plus at least one of the following: (1) clinically evident GO and/or dermopathy, (2) detectable serum TRAb, or (3) diffuse radioactive iodine uptake on thyroid scan.

Diagnostic evaluation should include

  • The initial test to screen patients with symptoms of hyperthyroidism is a serum TSH. A low or undetectable level (normal levels 0.4-4 mU/L) should prompt testing of serum-free thyroxin (fT4) and total triiodothyronine (tT3). A suppressed TSH with a high serum fT4 and/or tT3 confirms primary hyperthyroidism. Note that it is important to test T3 since some patients develop T3 toxicosis and may have normal or low fT4 levels.

  • Serologic markers: Though not necessary for the diagnosis, thyroid antibodies are present in most patients. While the TRAbs that cause GD are not easily measured, if high-sensitivity assays are used, they are detectable in over 95% of patients. TRAbs must be tested in pregnant women with a history of GD as high levels confer risk for neonatal Graves since TRAbs pass the placenta. In addition, thyroid peroxidase antibodies (TPOAbs) are positive in about three-quarters of patients and thyroglobulin antibodies (TgAbs) in about half of patients.

  • Thyroid examination: A diffuse, firm enlargement of thyroid gland is present in most patients and is more common in patients younger than 50 years old. In some patients a bruit can be auscultated over the thyroid because of the increased blood flow to the gland.

  • Imaging studies:

    • Radioactive iodine uptake scan can help distinguish GD from thyrotoxicosis caused by painless thyroiditis or postpartum thyroiditis, toxic multinodular goiter, toxic adenoma, and surreptitious ingestion of thyroid hormones. In GD there is a homogenous increase in radioiodine uptake whereas in the other forms of thyrotoxicosis there is a low or focal radioiodine uptake.

    • Ultrasound with Doppler may also help in the differential diagnosis with other causes of thyrotoxicosis; an increased blood flow to the gland is consistent with GD while low flow with destructive thyroiditis (painless or postpartum thyroiditis or some forms of drug-induced thyroiditis).

    • CT scan of the neck: In patients with symptoms of airway compromise, a computed tomographic (CT) scan of the neck should be done.

Hashimoto Thyroiditis

Diagnosis is made in a patient with primary hypothyroidism plus evidence of autoimmunity.

Diagnostic evaluation should include

Jun 2, 2016 | Posted by in HUMAN BIOLOGY & GENETICS | Comments Off on 60: Autoimmune Thyroid Diseases

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