Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which
the thyroid gland is attacked by a variety of cell- and antibody-mediated immune processes.
It was the first disease to be recognized as an autoimmune disease. It was first described
by the Japanese specialist Hakaru Hashimoto in Germany in 1912.
Signs and symptoms Hashimoto's thyroiditis very often results
in hypothyroidism with bouts of hyperthyroidism. Symptoms of Hashimoto's thyroiditis include
weight gain, depression, mania, sensitivity to heat and cold, paresthesia, chronic fatigue,
panic, bradycardia, tachycardia, congestive heart failure, high cholesterol, reactive
hypoglycemia, constipation, migraines, muscle weakness, joint stiffness, menorrhagia, myxedematous
psychosis, cramps, memory loss, vision problems, infertility and hair loss.
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 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. Risk factors
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. In addition Hashimoto's thyroiditis may be
associated with CTLA-4 gene polymorphisms that result in reduced functioning of the
gene's products, which are associated with negative regulation of T-lymphocyte activity.
Downregulatory gene polymorphisms affecting CTLA4 are also associated with autoimmune
pathology seen in development of type I diabetes. The strong genetic component underscoring
this theory 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. Neither result was seen to a similar degree in dizygotic twins, offering
strong favour for high genetic aetiology. 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 patients with chromosomal disorders, including Turner, Down's, and Klinefelter
syndromes usually associated with autoantibodies against thyroglobulin and thyroperoxidase.
Progressive depletion of these cells as the cytotoxic immune response develops leads to
higher degrees of primary hypothyroidism, presenting with a poverty of T3/T4 levels,
and compensatory elevations of TSH. Recent research suggests a potential role
for HHV-6 in the development or triggering of Hashimoto's thyroiditis.
Pathophysiology 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 patients 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 in response to cell-mediated immune response
affected by helper T-lymphocytes 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. 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. 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. Diagnosis
Diagnosis is made by detecting elevated levels of anti-thyroid peroxidase antibodies in the
serum. Given the relatively non-specific symptoms
of initial hypothyroidism, Hashimoto's thyroiditis is often misdiagnosed as depression, cyclothymia,
PMS, chronic fatigue syndrome, fibromyalgia and, less frequently, as ED or an anxiety
disorder. On gross examination, there is often presentation of a hard goitre that is not
painful to the touch; other symptoms seen with hypothyroidism, such as periorbital myxedema,
depends on the current state of progression of the response, especially given the usually
gradual development of clinically relevant hypothyroidism. Testing for thyroid-stimulating
hormone, free T3, free T4, and the anti-thyroglobulin antibodies, anti-thyroid peroxidase antibodies
and anti-microsomal antibodies can help obtain an accurate diagnosis. Earlier assessment
of the patient may present with elevated levels of thyroglobulin owing to the transient thyrotoxicosis
as inflammation within the thyroid causes damage to the integrity of thyroid follicle
storage of thyroglobulin; TSH is increased as the pituitary tries to compensate for decreased
T4 .
This exposure of the body to substantial amounts of previously isolated thyroid enzymes is
thought to contribute to the exacerbation of tolerance breakdown, giving rise to the
more pronounced symptoms seen later in the disease. Lymphocytic infiltration of the thyrocyte-associated
tissues often leads to the histologically significant finding of germinal center development
within the thyroid gland. Hashimoto's when presenting as mania is known
as Prasad's syndrome after Ashok Prasad, the psychiatrist who first described it.
Treatment 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 patient's life. In the event that hypothyroidism is
caused by Hashimoto's thyroiditis, it is recommended that the TSH levels be kept under 3.0.
Selenium Although the current clinical practice guidelines
for hypothyroidism in adults do not indicate selenium supplementation, a 1-year study of
46 patients found supplementing 80μg per day of selenium slowed several markers of
disease progression. Another study comparing 100μg and 200μg doses of selenium combined
with levothyroxine in 88 female patients over 9 months found that 200μg was more effective.
A 2013 systemic review found there is still not enough evidence to definitively support
or refute the efficacy of selenium for Hashimoto's thyroiditis, and urges more clinical trials
are needed before efficacy can be proven. As a dietary supplement, the FDA recommends
at least 55μg per day of selenium for adults with a tolerable upper intake level of 400μg.
Low-level laser therapy According to a study published in 2013, near-infrared
low level laser therapy has been shown to be effective in phase two clinical trials
at improving thyroid function. Gluten-free diet
Preliminary studies have suggested a correlation between Hashimoto's thyroiditis and celiac
disease. While it has not been rigorously explored, there are anecdotal reports that
a gluten-free diet may reduce the autoimmune response responsible for thyroid degeneration.
A study published in January 2012 compared a group of confirmed celiac patients to a
control group of healthy individuals, starting a gluten-free diet and continuing for one
year. While there was a higher occurrence of thyroiditis found amongst the celiac group,
there was no reduction in their level of anti-TPO antibody, improvement in thyroid function,
or change in thyroid volume reduction after one year without gluten. The study mentions
that its results disagree with other studies, such as a prospective study published in August
2000 with 90 celiac patients, which found that thyroid-related serum antibodies tended
to reduce during a gluten-free diet. Prognosis
Overt, symptomatic thyroid dysfunction is the most common complication, with about 5%
of patients with subclinical hypothyroidism and chronic autoimmune thyroiditis progressing
to thyroid failure every year. Transient periods of thyrotoxicosis sometimes occur, and rarely
the illness may progress to full hyperthyroid Basedow-Graves disease with active orbitopathy.
Rare cases of fibrous autoimmune thyroiditis present with severe dyspnea and dysphagia,
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 patients, and it is more likely to affect those with long-standing autoimmune
thyroiditis. Epidemiology
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. An average of 1 to 1.5 in
1000 people have this disease. 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.
History
Also known as Hashimoto's disease, Hashimoto's thyroiditis is named after the Japanese physician
Hakaru Hashimoto of the medical school at Kyushu University, who first described the
symptoms of patients 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
more commonly seen in areas of iodine deficiency that was occurring in the developed world,
and without evident causation by dietary deficiency. See also
Thyroid gland Thyroid lymphoma
Myxedematous psychosis Autoimmune thyroiditis
References
External links Autoimmune Thyroid Disease For details about
Autoimmune Thyroid Disease Hashimoto's disease at the Mayo Clinic
Sasaki, N; Takahashi, A; Nakano, N; Saito, T. "A case of 'hallucination of soliloquy'
with hypothyroidism induced Hashimoto disease. Meaning of psychopathological research about
symptomatic psychosis". Seishin shinkeigaku zasshi 103: 185–96. PMID 11326441.
Hall, Richard C.W.; Popkin, Michael K.; Devaul, Richard; Hall, Anne K.; Gardner, Earl R.;
Beresford, Thomas P.. "Psychiatric manifestations of Hashimoto's thyroiditis". Psychosomatics
23: 337–42. doi:10.1016/S0033-3182(82)73397-3. PMID 6896238.