Hypothyroidism is a chronic disease associated with deficiency in the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Research is ongoing to ensure that more people with hypothyroidism are diagnosed and are given effective treatment, and to work out the best way to use levothyroxine so that patients get the best results. In addition, many people with hypothyroidism do not know they have it. Levothyroxine replaces the person’s levels of thyroid hormone and makes them feel better, but the dose often needs to be adjusted for the best effect. Most people with hypothyroidism will need to take levothyroxine for a long time, perhaps even for the rest of their lives. This is an autoimmune disease in which the person’s immune system produces cells and antibodies that attack the thyroid gland. In areas of the world where people ingest enough iodine, the most common cause of hypothyroidism is Hashimoto’s disease. Thus, many countries try to increase iodine intake by adding iodine to salt. In underdeveloped parts of the world, the main reason why people develop hypothyroidism is that they not getting enough iodine from food. People with hypothyroidism may have changes in body weight, and feel tired, weak or unhappy, all of which can reduce their quality of life. This can result in heart disease, infertility, and poor brain development in children. Hypothyroidism occurs when the thyroid gland, located in the neck, does not produce enough thyroid hormone for the body’s requirements. Hypothyroidism is one of the most common diseases worldwide, and levothyroxine is the usual medication prescribed to manage it. Plain Language Summary: Plain language summary available for this article. In order to ensure this, further research should include more accurate assessments of the true prevalence of hypothyroidism in the community, optimisation of the levothyroxine substitution dose, proper duration of treatment, and identification of patients who may benefit from combination therapy with levothyroxine plus levotriiodothyronine. Because nearly one-third of patients with treated hypothyroidism still exhibit symptoms, it is important that levothyroxine is used more appropriately to achieve maximum benefit for patients. We here summarise the history of levothyroxine and discuss future issues regarding the optimal treatment of hypothyroidism. In adults with overt hypothyroidism, levothyroxine is usually prescribed at a starting dose of 1.6 µg/kg/day, which is then titrated to achieve optimal TSH levels (0.4–4.0 mIU/L), according to the therapeutic target. Levothyroxine has long been the main tool for treating hypothyroidism and is one of the world’s most widely prescribed medicines. Symptoms of hypothyroidism are non-specific and include mild to moderate weight gain, fatigue, poor concentration, depression, and menstrual irregularities, while the consequences of untreated or under-treated hypothyroidism include cardiovascular disease and increased mortality. Hypothyroidism is diagnosed biochemically, being overt primary hypothyroidism defined as serum thyroid-stimulating hormone (TSH) concentrations above and thyroxine concentrations below the normal reference range. Worldwide, environmental iodine deficiency is the most common cause of all thyroid disorders, including hypothyroidism, but in areas of iodine sufficiency, Hashimoto’s disease (chronic autoimmune thyroiditis) is the most common cause of thyroid failure. Over 99% of affected patients suffer from primary hypothyroidism. Hypothyroidism affects up to 5% of the general population, with a further estimated 5% being undiagnosed.
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