hypothyroidism hypothyroidism hypothyroidism (also called underactive thyroid, low thyroid or hypothyreosis) is a 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, slow heart rate, depression, and weight gain. occasionally there may be swelling of the front part of the neck due to goitre. untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome. not to be confused with hyperthyroidism. hypothyroidismother namesunderactive thyroid, low thyroid, hypothyreosismolecular structure of thyroxine, the deficiency of which causes the symptoms of hypothyroidismpronunciation/ˌhaɪpəˈθaɪrɔɪdɪzəm, -poʊ-/ specialtyendocrinologysymptomspoor ability to tolerate cold, feeling tired, constipation, weight gain, depression, anxiety, irritabilitycomplicationsduring pregnancy can result in cretinism in the babyusual onset< 60 years oldcausesiodine deficiency, hashimoto's thyroiditisdiagnostic methodblood tests (thyroid-stimulating hormone, thyroxine)differential diagnosisdepression, dementia, heart failure, chronic fatigue syndromepreventionsalt iodizationtreatmentlevothyroxinefrequency0.3–0.4% (usa) worldwide, too little iodine in the diet is the most common cause of hypothyroidism. hashimoto's thyroiditis is the most common cause of hypothyroidism in countries with sufficient dietary iodine. 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. salt iodization has prevented hypothyroidism in many populations. thyroid hormone replacement with levothyroxine treats hypothyroidism. medical professionals adjust the dose according to symptoms and normalization of the thyroxine and tsh levels. thyroid medication is safe in pregnancy. although an adequate amount of dietary iodine is important, too much may worsen specific forms 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 in men. people over the age of 60 are more commonly affected. dogs are also known to develop hypothyroidism, as are cats and horses, albeit more rarely. the word hypothyroidism is from greek hypo- 'reduced', thyreos 'shield', and eidos '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 goitre (enlarged thyroid gland). in middle-aged women, the symptoms may be mistaken for those of menopause. symptoms and signs of hypothyroidism symptoms signs fatigue dry, coarse skin feeling cold cool extremities poor memory and concentration myxedema (mucopolysaccharide deposits in the skin) constipation, dyspepsia hair loss weight gain with poor appetite slow pulse rate shortness of breath swelling of the limbs hoarse voice delayed relaxation of tendon reflexes in females, heavy menstrual periods (and later light periods) carpal tunnel syndrome abnormal sensation pleural effusion, ascites, pericardial effusion poor hearing 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 man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes and palloradditional symptoms include swelling of the arms and legs and ascites. myxedema coma is a rare but life-threatening state of extreme hypothyroidism. it may occur in those with established hypothyroidism when they develop an acute illness. myxedema coma can be the first presentation of hypothyroidism. people with myxedema coma typically have a 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 main article: thyroid disease in women even mild or subclinical hypothyroidism leads to possible infertility 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 is associated with gestational diabetes, low birth-weight, placental abruption, and the 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 goitre is rare, although it may develop later in children who have a thyroid gland that does not produce functioning thyroid hormone. a goitre 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: difficulty with 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 heartbeat. a goitre may be present with a completely enlarged thyroid gland; sometimes only part of the thyroid is enlarged and it can be knobby. related disorders thyroid hormone abnormalities are common in major psychiatric disorders including bipolar disorder; clinical research has shown there is a high rate of thyroid dysfunction in mood disorders and schizophrenia-spectrum disorders, concluding that there is a case for screening for the latter among people with thyroid illness. causes hypothyroidism is caused by inadequate function of the gland itself (primary hypothyroidism), inadequate stimulation by thyroid-stimulating hormone from the pituitary gland (secondary hypothyroidism), or inadequate release of thyrotropin-releasing hormone from the brain's hypothalamus (tertiary hypothyroidism). primary hypothyroidism is about a thousandfold more common than central hypothyroidism. central hypothyroidism is the name used for secondary and tertiary, since hypothalamus and pituitary gland are at the center of thyroid hormone control. iodine deficiency is the most common cause of primary hypothyroidism and endemic goitre 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 goitre. 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. a more uncommon cause of hypothyroidism is estrogen dominance. it is one of the most common hormone imbalance problems in women, but is not always link with hypothyroidism there are three different types of estrogens: estrone (e1), estradiol (e2), and estriol (e3), with estradiol being the most potent of the three women with estrogen dominance have estradiol levels of 115 pg/ml on day 3 of their cycle. however, estrogen dominance isn’t just about an over abundance of estradiol, but is more likely correlated with and imbalance between estradiol and progesterone. women who have to much unopposed estrogen, which is estrogen that does not have enough counterbalancing progesterone in their bodies, commonly have unbalanced thyroid levels, in addition to excess growths within their uterus. estradiol disrupts thyroid hormone production because high blood levels of estrogen signal the liver to increase the production of thyroid-binding globulin (tbg). this is an inhibitor protein that binds to the thyroid hormone, reducing the amount of t3 and t4 available for use by cells. without t3 and t4, the body's cellular function begins to slow down. 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 (hashimoto's) 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). iatrogenic hypothyroidism can be surgical (a result of thyroidectomy, usually for thyroid nodules or cancer) or following radioiodine ablation (usually for graves' disease). group causes primary hypothyroidism iodine deficiency (developing countries), autoimmune thyroiditis, subacute granulomatous thyroiditis, subacute lymphocytic thyroiditis, postpartum thyroiditis, previous thyroidectomy, acute infectious thyroiditis, previous radioiodine treatment, previous external beam radiotherapy to the neckmedication: lithium-based mood stabilizers, amiodarone, interferon alpha, tyrosine kinase inhibitors such as sunitinib central hypothyroidism lesions compressing the pituitary (pituitary adenoma, craniopharyngioma, meningioma, glioma, rathke's cleft cyst, metastasis, empty sella, aneurysm of the internal carotid artery), surgery or radiation to the pituitary, drugs, injury, vascular disorders (pituitary apoplexy, sheehan syndrome, subarachnoid hemorrhage), autoimmune diseases (lymphocytic hypophysitis, polyglandular disorders), infiltrative diseases (iron overload due to hemochromatosis or thalassemia, neurosarcoidosis, langerhans cell histiocytosis), particular inherited congenital disorders, and infections (tuberculosis, mycoses, syphilis) congenital hypothyroidism thyroid dysgenesis (75%), thyroid dyshormonogenesis (20%), maternal antibody or radioiodine transfersyndromes: mutations (in gnas complex locus, pax8, ttf-1/nkx2-1, ttf-2/foxe1), pendred's syndrome (associated with sensorineural hearing loss)transiently: due to maternal iodine deficiency or excess, anti-tsh receptor antibodies, certain congenital disorders, neonatal illnesscentral: pituitary dysfunction (idiopathic, septo-optic dysplasia, deficiency of pit1, isolated tsh deficiency) pathophysiology diagram of the hypothalamic–pituitary–thyroid axis. the hypothalamus secretes trh (green), which stimulates the production of tsh (red) by the pituitary gland. this, in turn, stimulates the production of thyroxine by the thyroid (blue). thyroxine levels decrease trh and tsh production by a negative feedback process. thyroid hormone is required for the normal functioning of numerous tissues in the body. in healthy individuals, 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%) are 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. diagnosis