increases in response to a decrease in negative feedback inhibition secondary to decreased serum thyroid hormones. typically, t4 is the preferred thyroid hormone test for hypothyroidism. 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 person's life. if hypothyroidism is caused by hashimoto's thyroiditis, the tsh levels may be recommended to be kept under 3.0 miu/l. prognosis overt, symptomatic thyroid dysfunction is the most common complication, with about 5% of people 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 shortness of breath and difficulty swallowing, resembling aggressive thyroid tumors, but such symptoms always improve with surgery or corticosteroid therapy. although primary thyroid b-cell lymphoma affects fewer than one in 1000 persons, it is more likely to affect those with long-standing autoimmune thyroiditis, as there is a 67- to 80-fold increased risk of developing primary thyroid lymphoma in patients with hashimoto's thyroiditis. epidemiology hashimoto's thyroiditis disorder is thought to be the most common cause of primary hypothyroidism in north america. within person, place, and time descriptive trends of epidemiology, it becomes more clear on how hashimoto's thyroiditis develops in and impacts differing populations. personal characteristic trends overall, hashimoto's thyroiditis affects up to 2% of the general population. about 5% of caucasians will develop hashimoto's at some point in their lives. in the us, the african-american population experiences it less commonly but has greater associated mortality. it is also less frequent in asian populations. about 1.0 to 1.5 in 1000 people have this disease at any time. it occurs between 8 and 15 times more often in women than in men. some research suggests a connection to the role of the placenta as an explanation for the sex difference. though it may occur at any age, including in children, it is most often observed in women between 30 and 60 years of age. the highest prevalence from one study was found in the elderly members of the community. those that already have an autoimmune disease are at greater risk of developing hashimoto's as the diseases generally coexist with each other. common diseases seen coexisting with hashimoto's include celiac disease, multiple sclerosis, type 1 diabetes, vitiligo, and rheumatoid arthritis. congenital hypothyroidism affects 1 in 3500-4000 newborns at birth and is a version of intellectual disability that can be treated if caught early, but can be hard to diagnose given that symptoms are minimal at a young age. congenital hypothyroidism is generally caused by defects of the thyroid gland, but for most cases in europe, asia, and africa, the iodine intake can cause hypothyroidism in newborns. geographic influence of dietary trends diets consisting of low or high iodine intake determine a population's risk of developing thyroid-related disorders. it is more common in regions of high iodine dietary intake, and among people who are genetically susceptible. geography plays a large role in which regions have access to diets with low or high iodine. iodine levels in both water and salt should be heavily monitored in order to protect at-risk populations from developing hypothyroidism. geographic trends of hypothyroidism vary across the world as different places have different ways of defining disease and reporting cases. populations that are spread out or defined poorly may skew data in unexpected ways. iodine deficiency disorder (idd) is combated using an increase in iodine in a person's diet. when a dramatic change occurs in a person's diet, they become more at-risk of developing hypothyroidism and other thyroid disorders. combatting idd with high salt intakes should be done carefully and cautiously as risk for hashimoto's may increase. if making modifications to one's diet, it is important to use a clinician's discretion to ensure that the dietary changes are the best option as recommendations can vary person to person. secular trends the secular trends of hypothyroidism reveal how the disease has changed over the course of time given changes in technology and treatment options. even though ultrasound technology and treatment options have improved, the incidence of hypothyroidism has increased according to data focused on the us and europe. between 1993 and 2001, per 1000 women, the disease was found varying between 3.9 and 4.89. between 1994 and 2001, per 1000 men, the disease increased from 0.65 to 1.01. changes in the definition of hypothyroidism and treatment options modify the incidence and prevalence of the disease overall. treatment using levothyroxine is individualized, and therefore allows the disease to be more manageable with time but does not work as a cure for the disease. history also known as hashimoto's disease, hashimoto's thyroiditis is named after 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 the german journal called archiv für klinische chirurgie. this paper was made up of 30 pages and 5 illustrations all describing the histological changes in the thyroid tissue. furthermore, all results in his first study were collected from four women. these results explained the pathological characteristics observed in these women especially the infiltration of lymphoid and plasma cells as well as the formation of lymphoid follicles with germinal centers, fibrosis, degenerated thyroid epithelial cells and leukocytes in the lumen. he described these traits to be histologically similar to those of mikulic's disease. as mentioned above, once he discovered these traits in this new disease, he named the disease struma lymphomatosa. this disease emphasized the lymphoid cell infiltration and formation of the lymphoid follicles with germinal centers, neither of which had ever been previously reported. despite dr. hashimoto's discovery and publication, the disease was unfortunately not recognized as distinct from reidel's thyroiditis, which was a common disease at that time in europe. although many other articles were reported and published by other researchers, hashimoto's struma lymphomatosa was only recognized as an early phase of reidel's thyroiditis in the early 1900s. it was not until 1931 that the disease was recognized as a disease in its own right, when researchers allen graham et al. from cleveland reported its symptoms and presentation in the same detailed manner as hakaru. in 1956, drs. rose and witebsky were able to demonstrate how immunization of certain rodents with extracts of other rodents' thyroid resembled the disease hakaru and other researchers were trying to describe. these doctors were also able to describe anti-thyroglobulin antibodies in blood serum samples from these same animals. later on in the same year, researchers from the middlesex hospital in london were able to perform human experiments on patients who presented with similar symptoms. they purified anti-thyroglobulin antibody from their serum and were able to conclude that these sick patients had an immunological reaction to human thyroglobulin. from this data, it was proposed that hashimoto's struma could be an autoimmune disease of the thyroid gland. in 1957, it was recognized as an autoimmune disorder and was the first organ-specific autoimmune disorder identified. following this recognition, the same researchers from middlesex hospital published an article in 1962 in the lancet that included a portrait of hakaru hashimoto. the disease became more well known from that moment, and hashimoto's disease started to appear more frequently in textbooks. since those discoveries, a number of autoimmune diseases have been discovered, with several of them having to do with thyroid-specific antibodies. pregnancy 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 herself and her infant if the disease goes 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 treat pregnant women only if they 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 ." hormonal changes and trophoblast expression of key immunomodulatory molecules lead to immunosuppression and fetal tolerance. main players in regulation of the immune response are tregs. both cell-mediated and humoral immune responses are attenuated, resulting in immune tolerance and suppression of autoimmunity. it has been reported that during pregnancy, levels of thyroid peroxidase and thyroglobulin antibodies decrease. after giving birth, tregs rapidly decrease and immune responses are re-established. it may lead to the occurrence or aggravation of the autoimmune thyroid disease. in up to 50% of females with thyroid peroxidase antibodies in the early pregnancy, thyroid autoimmunity in the postpartum period exacerbates in the form of postpartum thyroiditis. higher secretion of ifn-γ and il-4, and lower plasma cortisol concentration during pregnancy has been reported in females with postpartum thyroiditis than in healthy females. it indicates that weaker immunosuppression during pregnancy could contribute to the postpartum thyroid dysfunction. fetal microchimerism several years after the delivery, the chimeric male cells can be detected in the maternal peripheral blood, thyroid, lung, skin, or lymph nodes. the fetal immune cells in the maternal thyroid gland may become activated and act as a trigger that may initiate or exaggerate the autoimmune thyroid disease. in hashimoto's disease patients, fetal microchimeric cells were detected in thyroid in significantly higher numbers than in healthy females. other organisms hashimoto's disease is also known in chickens (gallus domesticus), rats (rattus rattus), mice (mus musculus), dogs (canis familiaris), and marmosets (callitrichidae).