Hashimoto’s thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto’s disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on there may be no symptoms. Over time the thyroid may enlarge forming a painless goiter. Some people eventually develop hypothyroidism with its accompanying weight gain, feeling tired, constipation, depression, and general pains. After many years the thyroid typically shrinks in size. Potential complications include thyroid lymphoma.
Hashimoto’s thyroiditis is thought to be due to a combination of genetic and environmental factors. Risk factors include a family history of the condition and having another autoimmune disease. Diagnosis is confirmed with blood tests for TSH, T4, and anti-thyroid autoantibodies. Other conditions that can produce similar symptoms include Graves’ disease and nontoxic nodular goiter.
Hashimoto’s thyroiditis is typically treated with levothyroxine. If hypothyroidism is not present some may recommend no treatment while others may treat to try to reduce the size of the goiter. Those affected should avoid eating large amounts of iodine; however, sufficient iodine is required especially during pregnancy. Surgery is rarely required to treat the goiter.
Hashimoto’s thyroiditis affects about 5% of the population at some point in their life. It typically begins between the ages of 30 and 50 and is much more common in women than men. Rates of disease appear to be increasing. It was first described by the Japanese physician Hakaru Hashimoto in 1912. In 1957 it was recognized as an autoimmune disorder.
Signs and symptoms
There are many symptoms that are attributed to Hashimoto’s thyroiditis or Hashimoto’s disease. The most common symptoms include the following: fatigue, weight gain, pale or puffy face, feeling cold, joint and muscle pain, constipation, dry and thinning hair, heavy menstrual flow or irregular periods, depression, panic disorder, a slowed heart rate, and problems getting pregnant and maintaining pregnancy.
Hashimoto’s disease is about seven times more common in women than in men. It can occur in teens and young women, but more commonly shows up in middle age, particularly for men. People who develop Hashimoto’s disease often have family members who have thyroid or other autoimmune diseases, and sometimes have other autoimmune diseases themselves.
The thyroid gland may become firm, large, and lobulated in Hashimoto’s thyroiditis, but changes in the thyroid can also be nonpalpable. Enlargement of the thyroid is due to lymphocytic infiltration and fibrosis rather than tissue hypertrophy. Physiologically, antibodies against thyroid peroxidase (TPO) (also called TPOAb) and/or thyroglobulin cause gradual destruction of follicles in the thyroid gland. Accordingly, the disease can be detected clinically by looking for these antibodies in the blood. It is also characterized by invasion of the thyroid tissue by leukocytes, mainly T-lymphocytes. A rare but serious complication is thyroid lymphoma, generally the B-cell type, non-Hodgkin lymphoma.
The strong genetic component is borne out in studies on monozygotic twins, with a concordance of 38-55%, with an even higher concordance of circulating thyroid antibodies not in relation to clinical presentation (up to 80% in monozygotic twins). Neither result was seen to a similar degree in dizygotic twins, offering strong favour for high genetic aetiology.
Hashimoto’s thyroiditis is associated with CTLA-4 (Cytotoxic T-lymphocyte Antigen-4) gene polymorphisms. CTLA-4 downregulates., i.e. transmits an inhibitory signal to T cells so reduced functioning is associated with increased T-lymphocyte activity. A family history of thyroid disorders is common, with the HLA-DR5 gene most strongly implicated conferring a relative risk of 3 in the UK.
Having other autoimmune diseases is a risk factor to develop Hashimoto’s thyroiditis, and the opposite is also true. Autoimmune diseases most commonly associated to Hashimoto’s thyroiditis include celiac disease, type 1 diabetes, vitiligo, and alopecia.
Preventable environmental factors, including high iodine intake, selenium deficiency, as well as infectious diseases and certain drugs, have been implicated in the development of autoimmune thyroid disease in genetically predisposed individuals.
The genes implicated vary in different ethnic groups and the incidence is increased in people with chromosomal disorders, including Turner, Down, and Klinefelter syndromes usually associated with autoantibodies against thyroglobulin and thyroperoxidase. Progressive depletion of these cells as the cytotoxic immune response leads to higher degrees of primary hypothyroidism, presenting with low T3/T4 levels, and compensatory elevations of TSH.
There are multiple suggested mechanisms by which the pathology of Hashimoto’s thyroiditis develops.
Various autoantibodies may be present against thyroid peroxidase, thyroglobulin and TSH receptors, although a small percentage of people may have none of these antibodies present. As indicated in various twin studies a percentage of the population may also have these antibodies without developing Hashimoto’s thyroiditis. Nevertheless, antibody-dependent cell-mediated cytotoxicity is a substantial factor behind the apoptotic fall-out of Hashimoto’s thyroiditis. Activation of cytotoxic T-lymphocytes (CD8+ T-cells) in response to cell-mediated immune response affected by helper T-lymphocytes (CD4+ T-cells) is central to thyrocyte destruction. As is characteristic of type IV hypersensitivities, recruitment of macrophages is another effect of the helper T-lymphocyte activation, with Th1 axis lymphocytes producing inflammatory cytokines within thyroid tissue to further macrophage activation and migration into the thyroid gland for direct effect.
Gross morphological changes within the thyroid are seen in the general enlargement which is far more locally nodular and irregular than more diffuse patterns (such as that of hyperthyroidism). While the capsule is intact and the gland itself is still distinct from surrounding tissue, microscopic examination can provide a more revealing indication of the level of damage.
Histologically, the hypersensitivity is seen as diffuse parenchymal infiltration by lymphocytes, particularly plasma B-cells, which can often be seen as secondary lymphoid follicles (germinal centers, not to be confused with the normally present colloid-filled follicles that constitute the thyroid). Atrophy of the colloid bodies is lined by Hürthle cells, cells with intensely eosinophilic, granular cytoplasm, a metaplasia from the normal cuboidal cells that constitute the lining of the thyroid follicles. Severe thyroid atrophy presents often with denser fibrotic bands of collagen that remains within the confines of the thyroid capsule.
Managing hormone levels
Hypothyroidism caused by Hashimoto’s thyroiditis is treated with thyroid hormone replacement agents such as levothyroxine, triiodothyronine or desiccated thyroid extract. A tablet taken once a day generally keeps the thyroid hormone levels normal. In most cases, the treatment needs to be taken for the rest of the person’s life. In the event that hypothyroidism is caused by Hashimoto’s thyroiditis, it may be recommended that the TSH levels be kept under 3.0 mIU/L.
Overt, symptomatic thyroid dysfunction is the most common complication, with about 5% of persons with subclinical hypothyroidism and chronic autoimmune thyroiditis progressing to thyroid failure every year. Transient periods of thyrotoxicosis (over-activity of the thyroid) sometimes occur, and rarely the illness may progress to full hyperthyroid Graves’ disease with active orbitopathy (bulging, inflamed eyes). Rare cases of fibrous autoimmune thyroiditis present with severe dyspnea (shortness of breath) and dysphagia (difficulty swallowing), resembling aggressive thyroid tumors – but such symptoms always improve with surgery or corticosteroid therapy. Primary thyroid B cell lymphoma affects fewer than one in a thousand persons, and it is more likely to affect those with long-standing autoimmune thyroiditis.
This disorder is believed to be the most common cause of primary hypothyroidism in North America; as a cause of non-endemic goiter, it is among the most common. Hashimoto’s thyroiditis affects about 5% of the population at some point in their life. About 1 to 1.5 in 1000 people have this disease at any point in time. It occurs between eight and fifteen times more often in women than in men. Though it may occur at any age, including in children, it is most often observed in women between 30 and 60 years of age. It is more common in regions of high iodine dietary intake, and among people who are genetically susceptible.
Also known as Hashimoto’s disease, Hashimoto’s thyroiditis is named after the Japanese physician Hakaru Hashimoto (1881−1934) of the medical school at Kyushu University, who first described the symptoms of persons with struma lymphomatosa, an intense infiltration of lymphocytes within the thyroid, in 1912 in a German publication. The report gave new insight into a condition (hypothyroidism) more commonly seen in areas of iodine deficiency that was occurring in the developed world, and without evident causation by dietary deficiency.
In 1957 it was recognized as an autoimmune disorder and was the first organ-specific one identified.
Pregnant women who are positive for Hashimoto’s thyroiditis may have decreased thyroid function or the gland may fail entirely. If a woman is TPOAb-positive, clinicians can inform her of the risks for themselves and their infants if they go untreated. “Thyroid peroxidase antibodies (TPOAb) are detected in 10% of pregnant women,” which presents risks to those pregnancies. Women who have low thyroid function that has not been stabilized are at greater risk of having an infant with: low birth weight, neonatal respiratory distress, hydrocephalus, hypospadias, miscarriage, and preterm delivery. The embryo transplantion rate and successful pregnancy outcomes are improved when Hashimoto’s is treated. Recommendations are to only treat pregnant women who are TPOAb-positive throughout the entirety of their pregnancies and to screen all pregnant women for thyroid levels. Close cooperation between the endocrinologist and obstetrician benefits the woman and the infant. The Endocrine Society recommends screening in pregnant women who are considered high-risk for thyroid autoimmune disease.
Thyroid peroxides antibodies testing is recommended for women who have ever been pregnant regardless of pregnancy outcome. “…revious pregnancy plays a major role in development of autoimmune overt hypothyroidism in premenopausal women, and the number of previous pregnancies should be taken into account when evaluating the risk of hypothyroidism in a young women .”