Hashimoto's thyroiditis

Hashimoto's thyroiditis
Classification and external resources
ICD-10	E06.3
ICD-9	245.2
OMIM	140300
DiseasesDB	5649
MedlinePlus	000371
eMedicine	med/949
MeSH	D050031

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.^[1] 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. ^{[citation needed]}

The thyroid gland may become firm, large, and lobulated in Hashimoto's thyroiditis, but changes in the thyroid can also be nonpalpable.^[2] Enlargement of the thyroid is due to lymphocytic infiltration and fibrosis rather than tissue hypertrophy. Physiologically, antibodies against thyroid peroxidase (TPO) 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. It is associated with non-Hodgkin lymphoma. ^{[citation needed]}

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 (Cytotoxic T-lymphocyte Associated-4) gene polymorphisms that result in reduced functioning of the gene's products, which are associated with negative regulation of T-lymphocyte activity.^[3] Downregulatory gene polymorphisms affecting CTLA4 are also associated with autoimmune pathology seen in development of Type I diabetes.^[4] 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 (up to 80% in monozygotic twins). Neither result was seen to a similar degree in dizygotic twins, offering strong favour for high genetic aetiology.^[5]

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.^[6] 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 (possibly variant A) in the development or triggering of Hashimoto's thyroiditis.^[7]

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 (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.^{[citation needed]}

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.^[8]

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.^[9]

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;^[8] 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 (TSH), Free T3, Free T4, and the anti-thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO) and anti-microsomal antibodies can help obtain an accurate diagnosis.^[10] 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 concomitantly decreased.^[11]

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.^[12]

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.^[13]

Selenium

Although the current clinical practice guidelines for hypothyroidism in adults do not indicate Selenium supplementation,^[14] a 1-year study of 46 patients found supplementing 80μg per day of Selenium slowed several markers of disease progression.^[15] 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.^[16] 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.^[17]

As a dietary supplement, the FDA recommends at least 55μg per day of Selenium for adults with a Tolerable Upper Intake Level of 400μg.^[18]

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 2 Clinical Trials at improving thyroid function.^[19]

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 (over-activity of the thyroid) sometimes occur, and rarely the illness may progress to full hyperthyroid Basedow-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 patients, and it is more likely to affect those with long-standing autoimmune thyroiditis.^[20]

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.^[21] An average of 1 to 1.5 in 1000 people have this disease.^[21] 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.^[20] It is more common in regions of high iodine dietary intake, and among people who are genetically susceptible.^[20]

History

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,^[22] who first described the symptoms of patients with struma lymphomatosa, an intense infiltration of lymphocytes within the thyroid, in 1912 in a German publication.^[23] 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.

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 (2001). "A case of 'hallucination of soliloquy' with hypothyroidism induced Hashimoto disease. Meaning of psychopathological research about symptomatic psychosis". Seishin shinkeigaku zasshi 103 (2): 185–96. PMID 11326441. 
• Hall, Richard C.W.; Popkin, Michael K.; Devaul, Richard; Hall, Anne K.; Gardner, Earl R.; Beresford, Thomas P. (April 1986). "Psychiatric manifestations of Hashimoto's thyroiditis". Psychosomatics 23 (4): 337–42. doi:10.1016/S0033-3182(82)73397-3. PMID 6896238. 

v t e Endocrine pathology: endocrine diseases (E00–E35, 240–259) Pancreas/ glucose metabolism Hypofunction Diabetes mellitus types: type 1 type 2 MODY 1 2 3 4 5 6 complications coma angiopathy ketoacidosis nephropathy neuropathy retinopathy cardiomyopathy insulin receptor (Rabson–Mendenhall syndrome) Insulin resistance Hyperfunction Hypoglycemia beta cell (Hyperinsulinism) G cell (Zollinger–Ellison syndrome) Hypothalamic/ pituitary axes Hypothalamus gonadotropin Kallmann syndrome Adiposogenital dystrophy CRH (Tertiary adrenal insufficiency) vasopressin (Neurogenic diabetes insipidus) general (Hypothalamic hamartoma) Pituitary Hyperpituitarism anterior Acromegaly Hyperprolactinaemia Pituitary ACTH hypersecretion posterior (SIADH) general (Nelson's syndrome) Hypopituitarism anterior Kallmann syndrome Growth hormone deficiency ACTH deficiency/Secondary adrenal insufficiency GnRH insensitivity FSH insensitivity LH/hCG insensitivity posterior (Neurogenic diabetes insipidus) general Empty sella syndrome Pituitary apoplexy Sheehan's syndrome Lymphocytic hypophysitis Thyroid Hypothyroidism Iodine deficiency Cretinism Congenital hypothyroidism Myxedema Euthyroid sick syndrome Hyperthyroidism Hyperthyroxinemia Thyroid hormone resistance Familial dysalbuminemic hyperthyroxinemia Hashitoxicosis Thyrotoxicosis factitia Graves' disease Thyroiditis Acute infectious Subacute De Quervain's Subacute lymphocytic Autoimmune/chronic Hashimoto's Postpartum Riedel's Goitre Endemic goitre Toxic nodular goitre Toxic multinodular goiter Thyroid nodule Parathyroid Hypoparathyroidism Hypoparathyroidism Pseudohypoparathyroidism Pseudopseudohypoparathyroidism Hyperparathyroidism Primary Secondary Tertiary Osteitis fibrosa cystica Adrenal Hyperfunction aldosterone: Hyperaldosteronism/Primary aldosteronism Conn syndrome Bartter syndrome Glucocorticoid remediable aldosteronism AME Liddle's syndrome 17α CAH cortisol: Cushing's syndrome (Pseudo-Cushing's syndrome) sex hormones: 21α CAH 11β CAH Hypofunction/ Adrenal insufficiency (Addison's, WF) aldosterone: Hypoaldosteronism 21α CAH 11β CAH cortisol: CAH Lipoid 3β 11β 17α 21α sex hormones: 17α CAH Gonads ovarian: Polycystic ovary syndrome Premature ovarian failure testicular: enzymatic 5α-reductase deficiency 17β-hydroxysteroid dehydrogenase deficiency aromatase excess syndrome) Androgen receptor (Androgen insensitivity syndrome general: Hypogonadism (Delayed puberty) Hypergonadism Precocious puberty Hypoandrogenism Hypoestrogenism Hyperandrogenism Hyperestrogenism Height Dwarfism/Short stature Midget Laron syndrome Psychosocial Ateliosis Gigantism Multiple Autoimmune polyendocrine syndrome multiple APS1 APS2 Carcinoid syndrome Multiple endocrine neoplasia 1 2A 2B Progeria Werner syndrome Acrogeria Metageria Woodhouse-Sakati syndrome M: END anat/phys/devp/horm noco (d)/cong/tumr, sysi/epon proc, drug (A10/H1/H2/H3/H5)

v t e Immune disorders: hypersensitivity and autoimmune diseases (279.5–6) Type I/allergy/atopy (IgE) Foreign Atopic eczema Allergic urticaria Allergic rhinitis (Hay fever) Allergic asthma Anaphylaxis Food allergy Milk Egg Peanut Tree nut Seafood Soy Wheat Penicillin allergy Autoimmune none Type II/ADCC IgM IgG Foreign Pernicious anemia Hemolytic disease of the newborn Autoimmune Cytotoxic Autoimmune hemolytic anemia Idiopathic thrombocytopenic purpura Bullous pemphigoid Pemphigus vulgaris Rheumatic fever Goodpasture's syndrome "Type 5"/receptor Graves' disease Myasthenia gravis Type III (Immune complex) Foreign Henoch–Schönlein purpura Hypersensitivity vasculitis Reactive arthritis Farmer's lung Post-streptococcal glomerulonephritis Serum sickness Arthus reaction Autoimmune Systemic lupus erythematosus Subacute bacterial endocarditis Rheumatoid arthritis Type IV/cell-mediated (T cells) Foreign Allergic contact dermatitis Mantoux test Autoimmune Diabetes mellitus type 1 Hashimoto's thyroiditis Guillain–Barré syndrome Multiple sclerosis Coeliac disease Giant-cell arteritis GVHD Transfusion-associated graft versus host disease Unknown/ multiple Foreign Hypersensitivity pneumonitis Allergic bronchopulmonary aspergillosis Transplant rejection Latex allergy (I+IV) Autoimmune Sjögren's syndrome Autoimmune hepatitis Autoimmune polyendocrine syndrome APS1 APS2 Autoimmune adrenalitis Systemic autoimmune disease M: LMC cell/phys/auag/auab/comp, igrc imdf/ipig/hyps/tumr proc, drug (L3/4)