Hypothyroidism, also called underactive thyroid or low thyroid, is a common disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone.It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, depression, and weight gain.Occasionally there may be swelling of the front part of the neck due to goitre.Untreated hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby, which is called cretinism. Worldwide, too little iodine in the diet is the most common cause of hypothyroidism.In countries with enough iodine in the diet, the most common cause of hypothyroidism is the autoimmune condition Hashimoto's thyroiditis.Less common causes include: previous treatment with radioactive iodine, injury to the hypothalamus or the anterior pituitary gland, certain medications, a lack of a functioning thyroid at birth, or previous thyroid surgery. The diagnosis of hypothyroidism, when suspected, can be confirmed with blood tests measuring thyroid-stimulating hormone (TSH) and thyroxine levels. Prevention at the population level has been with the universal salt iodization. Hypothyroidism can be treated with levothyroxine. The dose is adjusted according to symptoms and normalization of the thyroxine and TSH levels. Thyroid medication is safe in pregnancy. While a certain amount of dietary iodine is important, excessive amounts can worsen certain types of hypothyroidism. Worldwide about one billion people are estimated to be iodine deficient; however, it is unknown how often this results in hypothyroidism.In the United States, hypothyroidism occurs in 0.3–0.4% of people.Subclinical hypothyroidism, a milder form of hypothyroidism characterized by normal thyroxine levels and an elevated TSH level, is thought to occur in 4.3–8.5% of people in the United States.Hypothyroidism is more common in women than men.People over the age of 60 are more commonly affected.Dogs are also known to develop hypothyroidism and in rare cases cats and horses can also have the disorder.The word "hypothyroidism" is from Greek hypo- meaning "reduced", thyreos for "shield", and eidos for "form." Signs and symptoms People with hypothyroidism often have no or only mild symptoms. Numerous symptoms and signs are associated with hypothyroidism, and can be related to the underlying cause, or a direct effect of having not enough thyroid hormones.Hashimoto's thyroiditis may present with the mass effect of a goiter (enlarged thyroid gland). Delayed relaxation after testing the ankle jerk reflex is a characteristic sign of hypothyroidism and is associated with the severity of the hormone deficit. Myxedema coma Myxedema coma is a rare but life-threatening state of extreme hypothyroidism. It may occur in those who are known to have hypothyroidism when they develop another illness, but it can be the first presentation of hypothyroidism. The illness is characterized by very low body temperature without shivering, confusion, a slow heart rate and reduced breathing effort. There may be physical signs suggestive of hypothyroidism, such as skin changes or enlargement of the tongue. Pregnancy Even mild or subclinical hypothyroidism has been associated with impaired fertility and an increased risk of miscarriage.Hypothyroidism in early pregnancy, even with limited or no symptoms, may increase the risk of pre-eclampsia, offspring with lower intelligence, and the risk of infant death around the time of birth.Women are affected by hypothyroidism in 0.3–0.5% of pregnancies.Subclinical hypothyroidism during pregnancy has also been associated with gestational diabetes and birth of the baby before 37 weeks of pregnancy. Children Newborn children with hypothyroidism may have normal birth weight and height (although the head may be larger than expected and the posterior fontanelle may be open). Some may have drowsiness, decreased muscle tone, a hoarse-sounding cry, feeding difficulties, constipation, an enlarged tongue, umbilical hernia, dry skin, a decreased body temperature and jaundice.A goiter is rare, although it may develop later in children who have a thyroid gland that does not produce functioning thyroid hormone.A goiter may also develop in children growing up in areas with iodine deficiency.Normal growth and development may be delayed, and not treating infants may lead to an intellectual impairment (IQ 6–15 points lower in severe cases). Other problems include the following: large scale and fine motor skills and coordination, reduced muscle tone, squinting, decreased attention span, and delayed speaking.Tooth eruption may be delayed. In older children and adolescents, the symptoms of hypothyroidism may include fatigue, cold intolerance, sleepiness, muscle weakness, constipation, a delay in growth, overweight for height, pallor, coarse and thick skin, increased body hair, irregular menstrual cycles in girls, and delayed puberty. Signs may include delayed relaxation of the ankle reflex and a slow heart beat.A goiter may be present with a completely enlarged thyroid gland;sometimes only part of the thyroid is enlarged and it can be knobby in character. Causes Hypothyroidism is caused by inadequate function of the gland itself (primary hypothyroidism) or by not enough stimulation by thyroid-stimulating hormone (central hypothyroidism). Primary hypothyroidism is about a thousandfold more common than central hypothyroidism. Iodine deficiency is the most common cause of primary hypothyroidism and endemic goiter worldwide.In areas of the world with sufficient dietary iodine, hypothyroidism is most commonly caused by the autoimmune disease Hashimoto's thyroiditis (chronic autoimmune thyroiditis).Hashimoto's may be associated with a goiter. It is characterized by infiltration of the thyroid gland with T lymphocytes and autoantibodies against specific thyroid antigens such as thyroid peroxidase, thyroglobulin and the TSH receptor. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards.This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid. Autoimmune thyroiditis is associated with other immune-mediated diseases such as diabetes mellitus type 1, pernicious anemia, myasthenia gravis, celiac disease, rheumatoid arthritis and systemic lupus erythematosus.It may occur as part of autoimmune polyendocrine syndrome (type 1 and type 2). Pathophysiology Thyroid hormone is required for the normal functioning of numerous tissues in the body. In health, the thyroid gland predominantly secretes thyroxine (T4), which is converted into triiodothyronine (T3) in other organs by the selenium-dependent enzyme iodothyronine deiodinase.Triiodothyronine binds to the thyroid hormone receptor in the nucleus of cells, where it stimulates the turning on of particular genes and the production of specific proteins.Additionally, the hormone binds to integrin αvβ3 on the cell membrane, thereby stimulating the sodium–hydrogen antiporter and processes such as formation of blood vessels and cell growth.In blood, almost all thyroid hormone (99.97%) is bound to plasma proteins such as thyroxine-binding globulin; only the free unbound thyroid hormone is biologically active. The thyroid gland is the only source of thyroid hormone in the body; the process requires iodine and the amino acid tyrosine. Iodine in the bloodstream is taken up by the gland and incorporated into thyroglobulin molecules. The process is controlled by the thyroid-stimulating hormone (TSH, thyrotropin), which is secreted by the pituitary. Not enough iodine, or not enough TSH, can result in decreased production of thyroid hormones. The hypothalamic–pituitary–thyroid axis plays a key role in maintaining thyroid hormone levels within normal limits. Production of TSH by the anterior pituitary gland is stimulated in turn by thyrotropin-releasing hormone (TRH), released from the hypothalamus. Production of TSH and TRH is decreased by thyroxine by a negative feedback process. Not enough TRH, which is uncommon, can lead to not enough TSH and thereby to not enough thyroid hormone production. Pregnancy leads to marked changes in thyroid hormone physiology. The gland is increased in size by 10%, thyroxine production is increased by 50%, and iodine requirements are increased. Many women have normal thyroid function but have immunological evidence of thyroid autoimmunity (as evidenced by autoantibodies) or are iodine deficient, and develop evidence of hypothyroidism before or after giving birth.