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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 hormones.[3] 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.[3] Occasionally there may be swelling of the front part of the neck due to goitre.[3] Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.[5]

Hypothyroidism
Other namesUnderactive thyroid, low thyroid, hypothyreosis
Molecular structure of thyroxine, which is deficient in hypothyroidism
Pronunciation
SpecialtyEndocrinology
SymptomsPoor ability to tolerate cold, feeling tired, constipation, weight gain,[3] depression, anxiety, irritability[4]
ComplicationsDuring pregnancy can result in cretinism in the baby[5]
Usual onset< 60 years old[3]
CausesIodine deficiency, Hashimoto's thyroiditis[3]
Diagnostic methodBlood tests (thyroid-stimulating hormone, thyroxine)[3]
Differential diagnosisDepression, dementia, heart failure, chronic fatigue syndrome[6]
PreventionSalt iodization[7]
TreatmentLevothyroxine[3]
Frequency0.3–0.4% (USA)[8]

Worldwide, too little iodine in the diet is the most common cause of hypothyroidism.[8][9] Hashimoto's thyroiditis is the most common cause of hypothyroidism in countries with sufficient dietary iodine.[3] 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.[3][10] The diagnosis of hypothyroidism, when suspected, can be confirmed with blood tests measuring thyroid-stimulating hormone (TSH) and thyroxine levels.[3]

Salt iodization has prevented hypothyroidism in many populations.[7] Thyroid hormone replacement with levothyroxine treats hypothyroidism.[3] Medical professionals adjust the dose according to symptoms and normalization of the thyroxine and TSH levels.[3] Thyroid medication is safe in pregnancy.[3] Although an adequate amount of dietary iodine is important, too much may worsen specific forms of hypothyroidism.[3]

Worldwide about one billion people are estimated to be iodine-deficient; however, it is unknown how often this results in hypothyroidism.[11] In the United States, hypothyroidism occurs in 0.3–0.4% of people.[8] 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.[8] Hypothyroidism is more common in women than in men.[3] People over the age of 60 are more commonly affected.[3] Dogs are also known to develop hypothyroidism, as are cats and horses, albeit more rarely.[12] The word hypothyroidism is from Greek hypo- 'reduced', thyreos 'shield', and eidos 'form'.[13]

Signs and symptoms edit

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.[14][15] Hashimoto's thyroiditis may present with the mass effect of a goitre (enlarged thyroid gland).[14] In middle-aged women, the symptoms may be mistaken for those of menopause.[16]

 
Symptoms and signs of hypothyroidism[14]
Symptoms[14] Signs[14]
Fatigue Dry, coarse skin
Feeling cold Cool extremities
Poor memory and concentration Myxedema (mucopolysaccharide deposits in the skin)
Constipation, dyspepsia[17] 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
Muscle weakness

Delayed relaxation after testing the ankle jerk reflex is a characteristic sign of hypothyroidism and is associated with the severity of the hormone deficit.[8]

Myxedema coma edit

 
Man with myxedema or severe hypothyroidism showing an expressionless face, puffiness around the eyes and pallor
 
Additional 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.[18]

Pregnancy edit

Even mild or subclinical hypothyroidism leads to possible infertility and an increased risk of miscarriage.[19][20] Hypothyroidism in early pregnancy, even with limited or no symptoms, may increase the risk of pre-eclampsia, offspring with lower intelligence,[21][22][23][24] and the risk of infant death around the time of birth.[19][20][25] Women are affected by hypothyroidism in 0.3–0.5% of pregnancies.[25] 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.[21][26][27][28]

Children edit

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, poor weight gain, a hoarse-sounding cry, feeding difficulties, constipation, an enlarged tongue, umbilical hernia, dry skin, a decreased body temperature, and jaundice.[29] A goiter is rare, although it may develop later in children who have a thyroid gland that does not produce functioning thyroid hormone.[29] A goitre may also develop in children growing up in areas with iodine deficiency.[30] 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.[29] Tooth eruption may be delayed.[31]

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.[29] A goiter may be present with a completely enlarged thyroid gland;[29] sometimes only part of the thyroid is enlarged and it can be knobby.[32]

Related disorders edit

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.[33]

Causes edit

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).[8][34] Primary hypothyroidism is about a thousandfold more common than central hypothyroidism.[10] 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.[8][9] In areas of the world with sufficient dietary iodine, hypothyroidism is most commonly caused by the autoimmune disease Hashimoto's thyroiditis (chronic autoimmune thyroiditis).[8][9] 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.[8]

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[35] There are three different types of estrogens: estrone (E1), estradiol (E2), and estriol (E3), with estradiol being the most potent of the three[35][failed verification] Women with estrogen dominance have estradiol levels of 115 pg/ml on day 3 of their cycle. However, estrogen dominance is not just about an over abundance of estradiol, but is more likely correlated with an imbalance between estradiol and progesterone. Women who have too 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 uteri.[36]

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.[37] 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.[38] This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.[38]

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.[8] It may occur as part of autoimmune polyendocrine syndrome (type 1 and type 2).[8]

Iatrogenic hypothyroidism can be surgical (a result of thyroidectomy, usually for thyroid nodules or cancer) or following radioiodine ablation (usually for Graves' disease).

Type of hypothyroidism Causes
Primary hypothyroidism[8] Iodine deficiency (developing countries), autoimmune thyroiditis, subacute granulomatous thyroiditis, subacute lymphocytic thyroiditis, postpartum thyroiditis, previous thyroidectomy, acute infectious thyroiditis,[39] previous radioiodine treatment, previous external beam radiotherapy to the neck
Medication: lithium-based mood stabilizers, amiodarone, interferon alpha, tyrosine kinase inhibitors such as sunitinib
Central hypothyroidism[10] 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[40] Thyroid dysgenesis (75%), thyroid dyshormonogenesis (20%), maternal antibody or radioiodine transfer
Syndromes: 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 illness
Central: pituitary dysfunction (idiopathic, septo-optic dysplasia, deficiency of PIT1, isolated TSH deficiency)

Pathophysiology edit

 
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.[41] 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.[42] 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.[42] 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.[8]

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.[34]

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.[10]

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.[43]

Diagnosis edit

Laboratory testing of thyroid stimulating hormone levels in the blood is considered the best initial test for hypothyroidism; a second TSH level is often obtained several weeks later for confirmation.[44] Levels may be abnormal in the context of other illnesses, and TSH testing in hospitalized people is discouraged unless thyroid dysfunction is strongly suspected[8] as the cause of the acute illness.[16] An elevated TSH level indicates that the thyroid gland is not producing enough thyroid hormone, and free T4 levels are then often obtained.[8][16][32] Measuring T3 is discouraged by the AACE in the assessment for hypothyroidism.[8] In England and Wales, the National Institute for Health and Care Excellence (NICE) recommends routine T4 testing in children, and T3 testing in both adults and children if central hypothyroidism is suspected and the TSH is low.[16] There are a number of symptom rating scales for hypothyroidism; they provide a degree of objectivity but have limited use for diagnosis.[8]

TSH T4 Interpretation
Normal Normal Normal thyroid function
Elevated Low Overt hypothyroidism
Normal/low Low Central hypothyroidism
Elevated Normal Subclinical hypothyroidism

Many cases of hypothyroidism are associated with mild elevations in creatine kinase and liver enzymes in the blood. They typically return to normal when hypothyroidism has been fully treated.[8] Levels of cholesterol, low-density lipoprotein and lipoprotein (a) can be elevated;[8] the impact of subclinical hypothyroidism on lipid parameters is less well-defined.[30]

Very severe hypothyroidism and myxedema coma are characteristically associated with low sodium levels in the blood together with elevations in antidiuretic hormone, as well as acute worsening of kidney function due to a number of causes.[18] In most causes, however, it is unclear if the relationship is causal.[45]

A diagnosis of hypothyroidism without any lumps or masses felt within the thyroid gland does not require thyroid imaging; however, if the thyroid feels abnormal, diagnostic imaging is then recommended.[44] The presence of antibodies against thyroid peroxidase (TPO) makes it more likely that thyroid nodules are caused by autoimmune thyroiditis, but if there is any doubt, a needle biopsy may be required.[8]

Central edit

If the TSH level is normal or low and serum free T4 levels are low, this is suggestive of central hypothyroidism (not enough TSH or TRH secretion by the pituitary gland or hypothalamus). There may be other features of hypopituitarism, such as menstrual cycle abnormalities and adrenal insufficiency. There might also be symptoms of a pituitary mass such as headaches and vision changes. Central hypothyroidism should be investigated further to determine the underlying cause.[10][44]

Overt edit

In overt primary hypothyroidism, TSH levels are high and T4 and T3 levels are low. Overt hypothyroidism may also be diagnosed in those who have a TSH on multiple occasions of greater than 5mIU/L, appropriate symptoms, and only a borderline low T4.[46] It may also be diagnosed in those with a TSH of greater than 10mIU/L.[46]

Subclinical edit

Subclinical hypothyroidism is a biochemical diagnosis characterized by an elevated serum TSH level, but with a normal serum free thyroxine level.[47][48][49] The incidence of subclinical hypothyroidism is estimated to be 3-15% and a higher incidence is seen in elderly people, females and those with lower iodine levels.[47] Subclinical hypothyroidism is most commonly caused by autoimmune thyroid diseases, especially Hashimoto's thyroiditis.[50] The presentation of subclinical hypothyroidism is variable and classic signs and symptoms of hypothyroidism may not be observed.[48] Of people with subclinical hypothyroidism, a proportion will develop overt hypothyroidism each year. In those with detectable antibodies against thyroid peroxidase (TPO), this occurs in 4.3%, while in those with no detectable antibodies, this occurs in 2.6%.[8] In addition to detectable anti-TPO antibodies, other risk factors for conversion from subclinical hypothyroidism to overt hypothyroidism include female sex or in those with higher TSH levels or lower level of normal free T4 levels.[47] Those with subclinical hypothyroidism and detectable anti-TPO antibodies who do not require treatment should have repeat thyroid function tested more frequently (e.g. every 6 months) compared with those who do not have antibodies.[44][47]

Pregnancy edit

During pregnancy, the thyroid gland must produce 50% more thyroid hormone to provide enough thyroid hormone for the developing fetus and the expectant mother.[28] In pregnancy, free thyroxine levels may be lower than anticipated due to increased binding to thyroid binding globulin and decreased binding to albumin. They should either be corrected for the stage of pregnancy,[43] or total thyroxine levels should be used instead for diagnosis.[8] TSH values may also be lower than normal (particularly in the first trimester) and the normal range should be adjusted for the stage of pregnancy.[8][43]

In pregnancy, subclinical hypothyroidism is defined as a TSH between 2.5 and 10 mIU/L with a normal thyroxine level, while those with TSH above 10 mIU/L are considered to be overtly hypothyroid even if the thyroxine level is normal.[43] Antibodies against TPO may be important in making decisions about treatment, and should, therefore, be determined in women with abnormal thyroid function tests.[8]

Determination of TPO antibodies may be considered as part of the assessment of recurrent miscarriage, as subtle thyroid dysfunction can be associated with pregnancy loss,[8] but this recommendation is not universal,[51] and presence of thyroid antibodies may not predict future outcome.[52]

Prevention edit

 
A 3-month-old infant with untreated congenital hypothyroidism showing myxedematous facies, a big tongue, and skin mottling

Hypothyroidism may be prevented in a population by adding iodine to commonly used foods. This public health measure has eliminated endemic childhood hypothyroidism in countries where it was once common. In addition to promoting the consumption of iodine-rich foods such as dairy and fish, many countries with moderate iodine deficiency have implemented universal salt iodization.[53] Encouraged by the World Health Organization,[54] 70% of the world's population across 130 countries are receiving iodized salt. In some countries, iodized salt is added to bread.[53] Despite this, iodine deficiency has reappeared in some Western countries as a result of attempts to reduce salt intake.[53]

Pregnant and breastfeeding women, who require 66% more daily iodine than non-pregnant women, may still not be getting enough iodine.[53][55] The World Health Organization recommends a daily intake of 250 µg for pregnant and breastfeeding women.[56] As many women will not achieve this from dietary sources alone, the American Thyroid Association recommends a 150 µg daily supplement by mouth.[43][57]

Screening edit

Screening for hypothyroidism is performed in the newborn period in many countries, generally using TSH. This has led to the early identification of many cases and thus the prevention of developmental delay.[58] It is the most widely used newborn screening test worldwide.[59] While TSH-based screening will identify the most common causes, the addition of T4 testing is required to pick up the rarer central causes of neonatal hypothyroidism.[29] If T4 determination is included in the screening done at birth, this will identify cases of congenital hypothyroidism of central origin in 1:16,000 to 1:160,000 children. Considering that these children usually have other pituitary hormone deficiencies, early identification of these cases may prevent complications.[10]

In adults, widespread screening of the general population is a matter of debate. Some organizations (such as the United States Preventive Services Task Force) state that evidence is insufficient to support routine screening,[60] while others (such as the American Thyroid Association) recommend either intermittent testing above a certain age in all sexes or only in women.[8] Targeted screening may be appropriate in a number of situations where hypothyroidism is common: other autoimmune diseases, a strong family history of thyroid disease, those who have received radioiodine or other radiation therapy to the neck, those who have previously undergone thyroid surgery, those with an abnormal thyroid examination, those with psychiatric disorders, people taking amiodarone or lithium, and those with a number of health conditions (such as certain heart and skin conditions).[8] Yearly thyroid function tests are recommended in people with Down syndrome, as they are at higher risk of thyroid disease.[61] Guidelines for England and Wales from the National Institute for Health and Care Excellence (NICE) recommend testing for thyroid disease in people with type 1 diabetes and new-onset atrial fibrillation, and suggests testing in those with depression or unexplained anxiety (all ages), in children with abnormal growth, or unexplained change in behaviour or school performance.[16] On diagnosis of autoimmune thyroid disease, NICE also recommends screening for celiac disease.[62]

Management edit

Hormone replacement edit

Most people with hypothyroidism symptoms and confirmed thyroxine deficiency are treated with a synthetic long-acting form of thyroxine, known as levothyroxine (L-thyroxine).[8][15] In young and otherwise healthy people with overt hypothyroidism, a full replacement dose (adjusted by weight) can be started immediately; in the elderly and people with heart disease a lower starting dose is recommended to prevent over supplementation and risk of complications.[8][34][16] Lower doses may be sufficient in those with subclinical hypothyroidism, while people with central hypothyroidism may require a higher than average dose.[8]

Blood free thyroxine and TSH levels are monitored to help determine whether the dose is adequate. This is done 4–8 weeks after the start of treatment or a change in levothyroxine dose. Once the adequate replacement dose has been established, the tests can be repeated after 6 and then 12 months, unless there is a change in symptoms.[8] Normalization of TSH does not mean that other abnormalities associated with hypothyroidism improve entirely, such as elevated cholesterol levels.[63]

In people with central/secondary hypothyroidism, TSH is not a reliable marker of hormone replacement and decisions are based mainly on the free T4 level.[8][10] Levothyroxine is best taken 30–60 minutes before breakfast, or four hours after food,[8] as certain substances such as food and calcium can inhibit the absorption of levothyroxine.[64] There is no direct way of increasing thyroid hormone secretion by the thyroid gland.[15]

Liothyronine edit

Treatment with liothyronine alone has not received enough study to make a recommendation as to its use; due to its shorter half-life it would need to be taken more often than levothyroxine.[8]

Adding liothyronine (synthetic T3) to levothyroxine has been suggested as a measure to provide better symptom control, but this has not been confirmed by studies.[9][15][65] In 2007, the British Thyroid Association stated that combined T4 and T3 therapy carried a higher rate of side effects and no benefit over T4 alone.[15][66] Similarly, American guidelines discourage combination therapy due to a lack of evidence, although they acknowledge that some people feel better when receiving combination treatment.[8] Guidelines by NICE for England and Wales discourage liothyronine.[16]

People with hypothyroidism who do not feel well despite optimal levothyroxine dosing may request adjunctive treatment with liothyronine. A 2012 guideline from the European Thyroid Association recommends that support should be offered with regards to the chronic nature of the disease and that other causes of the symptoms should be excluded. Addition of liothyronine should be regarded as experimental, initially only for a trial period of 3 months, and in a set ratio to the current dose of levothyroxine.[67] The guideline explicitly aims to enhance the safety of this approach and to counter its indiscriminate use.[67]

Desiccated animal thyroid edit

Desiccated thyroid extract is an animal-based thyroid gland extract,[15] most commonly from pigs. It is a combination therapy, containing forms of T4 and T3.[15] It also contains calcitonin (a hormone produced in the thyroid gland involved in the regulation of calcium levels), T1 and T2; these are not present in synthetic hormone medication.[68] This extract was once a mainstream hypothyroidism treatment, but its use today is unsupported by evidence;[9][15] British Thyroid Association and American professional guidelines discourage its use,[8][66] as does NICE.[16]

Subclinical hypothyroidism edit

There is no evidence of a benefit from treating subclinical hypothyroidism in those who are not pregnant, and there are potential risks of overtreatment.[69] Untreated subclinical hypothyroidism may be associated with a modest increase in the risk of coronary artery disease when the TSH is over 10 mIU/L.[69][70] A 2007 review found no benefit of thyroid hormone replacement except for "some parameters of lipid profiles and left ventricular function".[71] There is no association between subclinical hypothyroidism and an increased risk of bone fractures,[72] nor is there a link with cognitive decline.[73]

American guidelines recommend that treatment should be considered in people with symptoms of hypothyroidism, detectable antibodies against thyroid peroxidase, a history of heart disease or are at an increased risk for heart disease, if the TSH is elevated but below 10 mIU/L.[8] American guidelines further recommend universal treatment (independent of risk factors) in those with TSH levels that are markedly elevated; above 10 mIU/L because of an increased risk of heart failure or death due to cardiovascular disease.[8][47] NICE recommends that those with a TSH above 10 mIU/L should be treated in the same way as overt hypothyroidism. Those with an elevated TSH but below 10 mIU/L who have symptoms suggestive of hypothyroidism should have a trial of treatment but with the aim to stopping this if the symptoms persist despite normalisation of the TSH.[16]

A recent meta-analysis, however, found an increased risk for cardiovascular death in subclinical hypothyroidism.[74]

Myxedema coma edit

Myxedema coma or severe decompensated hypothyroidism usually requires admission to the intensive care, close observation and treatment of abnormalities in breathing, temperature control, blood pressure, and sodium levels. Mechanical ventilation may be required, as well as fluid replacement, vasopressor agents, careful rewarming, and corticosteroids (for possible adrenal insufficiency which can occur together with hypothyroidism). Careful correction of low sodium levels may be achieved with hypertonic saline solutions or vasopressin receptor antagonists.[18] For rapid treatment of the hypothyroidism, levothyroxine or liothyronine may be administered intravenously, particularly if the level of consciousness is too low to be able to safely swallow medication.[18] While administration through a nasogastric tube is possible, this may be unsafe and is discouraged.[18]

Pregnancy edit

In women with known hypothyroidism who become pregnant, it is recommended that serum TSH levels are closely monitored. Levothyroxine should be used to keep TSH levels within the normal range for that trimester. The first trimester normal range is below 2.5 mIU/L and the second and third trimesters normal range is below 3.0 mIU/L.[15][43] Treatment should be guided by total (rather than free) thyroxine or by the free T4 index. Similarly to TSH, the thyroxine results should be interpreted according to the appropriate reference range for that stage of pregnancy.[8] The levothyroxine dose often needs to be increased after pregnancy is confirmed,[8][34][43] although this is based on limited evidence and some recommend that it is not always required; decisions may need to based on TSH levels.[75]

Women with anti-TPO antibodies who are trying to become pregnant (naturally or by assisted means) may require thyroid hormone supplementation even if the TSH level is normal. This is particularly true if they have had previous miscarriages or have been hypothyroid in the past.[8] Supplementary levothyroxine may reduce the risk of preterm birth and possibly miscarriage.[76] The recommendation is stronger in pregnant women with subclinical hypothyroidism (defined as TSH 2.5–10 mIU/L) who are anti-TPO positive, in view of the risk of overt hypothyroidism. If a decision is made not to treat, close monitoring of the thyroid function (every 4 weeks in the first 20 weeks of pregnancy) is recommended.[8][43] If anti-TPO is not positive, treatment for subclinical hypothyroidism is not currently recommended.[43] It has been suggested that many of the aforementioned recommendations could lead to unnecessary treatment, in the sense that the TSH cutoff levels may be too restrictive in some ethnic groups; there may be little benefit from treatment of subclinical hypothyroidism in certain cases.[75]

Alternative medicine edit

The effectiveness and safety of using Chinese herbal medicines to treat hypothyroidism is not known.[77]

Epidemiology edit

Worldwide about one billion people are estimated to be iodine deficient; however, it is unknown how often this results in hypothyroidism.[11] In large population-based studies in Western countries with sufficient dietary iodine, 0.3–0.4% of the population have overt hypothyroidism. A larger proportion, 4.3–8.5%, have subclinical hypothyroidism.[8] Undiagnosed hypothyroidism is estimated to affect about 4–7% of community-derived populations in the US and Europe.[78] Of people with subclinical hypothyroidism, 80% have a TSH level below the 10 mIU/L mark regarded as the threshold for treatment.[49] Children with subclinical hypothyroidism often return to normal thyroid function, and a small proportion develops overt hypothyroidism (as predicted by evolving antibody and TSH levels, the presence of celiac disease, and the presence of a goitre).[79]

Women are more likely to develop hypothyroidism than men. In population-based studies, women were seven times more likely than men to have TSH levels above 10 mU/L.[8] 2–4% of people with subclinical hypothyroidism will progress to overt hypothyroidism each year. The risk is higher in those with antibodies against thyroid peroxidase.[8][49] Subclinical hypothyroidism is estimated to affect approximately 2% of children; in adults, subclinical hypothyroidism is more common in the elderly, and in White people.[48] There is a much higher rate of thyroid disorders, the most common of which is hypothyroidism, in individuals with Down syndrome[29][61] and Turner syndrome.[29]

Very severe hypothyroidism and myxedema coma are rare, with it estimated to occur in 0.22 per million people a year.[18] The majority of cases occur in women over 60 years of age, although it may happen in all age groups.[18]

Most hypothyroidism is primary in nature. Central/secondary hypothyroidism affects 1:20,000 to 1:80,000 of the population, or about one out of every thousand people with hypothyroidism.[10]

History edit

In 1811, Bernard Courtois discovered iodine was present in seaweed, and iodine intake was linked with goitre size in 1820 by Jean-Francois Coindet.[80] Gaspard Adolphe Chatin proposed in 1852 that endemic goitre was the result of not enough iodine intake, and Eugen Baumann demonstrated iodine in thyroid tissue in 1896.[80]

The first cases of myxedema were recognized in the mid-19th century (the 1870s), but its connection to the thyroid was not discovered until the 1880s when myxedema was observed in people following the removal of the thyroid gland (thyroidectomy).[81] The link was further confirmed in the late 19th century when people and animals who had had their thyroid removed showed improvement in symptoms with transplantation of animal thyroid tissue.[9] The severity of myxedema, and its associated risk of mortality and complications, created interest in discovering effective treatments for hypothyroidism.[81] Transplantation of thyroid tissue demonstrated some efficacy, but recurrences of hypothyroidism was relatively common, and sometimes required multiple repeat transplantations of thyroid tissue.[81]

In 1891, the English physician George Redmayne Murray introduced subcutaneously injected sheep thyroid extract,[82] followed shortly after by an oral formulation.[9][83] Purified thyroxine was introduced in 1914 and in the 1930s synthetic thyroxine became available, although desiccated animal thyroid extract remained widely used. Liothyronine was identified in 1952.[9]

Early attempts at titrating therapy for hypothyroidism proved difficult. After hypothyroidism was found to cause a lower basal metabolic rate, this was used as a marker to guide adjustments in therapy in the early 20th century (around 1915).[81] However, a low basal metabolic rate was known to be non-specific, also present in malnutrition.[81] The first laboratory test to be helpful in assessing thyroid status was the serum protein-bound iodine, which came into use around the 1950s.

In 1971, the thyroid stimulating hormone (TSH) radioimmunoassay was developed, which was the most specific marker for assessing thyroid status in patients.[81] Many people who were being treated based on basal metabolic rate, minimizing hypothyroid symptoms, or based on serum protein-bound iodine, were found to have excessive thyroid hormone.[81] The following year, in 1972, a T3 radioimmunoassay was developed, and in 1974, a T4 radioimmunoassay was developed.[81]

Other animals edit

 
Characteristic changes in the facial skin of a Labrador Retriever with hypothyroidism

In veterinary practice, dogs are the species most commonly affected by hypothyroidism. The majority of cases occur as a result of primary hypothyroidism, of which two types are recognized: lymphocytic thyroiditis, which is probably immune-driven and leads to destruction and fibrosis of the thyroid gland, and idiopathic atrophy, which leads to the gradual replacement of the gland by fatty tissue.[12][84] There is often lethargy, cold intolerance, exercise intolerance, and weight gain. Furthermore, skin changes and fertility problems are seen in dogs with hypothyroidism, as well as a number of other symptoms.[84] The signs of myxedema can be seen in dogs, with prominence of skin folds on the forehead, and cases of myxedema coma are encountered.[12] The diagnosis can be confirmed by blood test, as the clinical impression alone may lead to overdiagnosis.[12][84] Lymphocytic thyroiditis is associated with detectable antibodies against thyroglobulin, although they typically become undetectable in advanced disease.[84] Treatment is with thyroid hormone replacement.[12]

Other species that are less commonly affected include cats and horses, as well as other large domestic animals. In cats, hypothyroidism is usually the result of other medical treatment such as surgery or radiation. In young horses, congenital hypothyroidism has been reported predominantly in Western Canada and has been linked with the mother's diet.[12]

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External links edit

  • Hypothyroidism at Curlie
  • "Hypothyroidism information for patients". American Thyroid Association. Retrieved 2017-03-25.
  • "UK Guidelines for the use of thyroid function tests" (PDF). The Association for Clinical Biochemistry, British Thyroid Association and British Thyroid Foundation. 2006. Retrieved 2013-12-25.
  • Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S (March 2017). "2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum". Thyroid. 27 (3): 315–389. doi:10.1089/thy.2016.0457. PMC 3472679. PMID 28056690.

hypothyroidism, confused, with, hyperthyroidism, also, called, underactive, thyroid, thyroid, hypothyreosis, disorder, endocrine, system, which, thyroid, gland, does, produce, enough, thyroid, hormones, cause, number, symptoms, such, poor, ability, tolerate, c. Not to be confused with Hyperthyroidism 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 hormones 3 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 3 Occasionally there may be swelling of the front part of the neck due to goitre 3 Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome 5 HypothyroidismOther namesUnderactive thyroid low thyroid hypothyreosisMolecular structure of thyroxine which is deficient in hypothyroidismPronunciation ˌ h aɪ p e ˈ 8 aɪ r ɔɪ d ɪ z em p oʊ 1 2 SpecialtyEndocrinologySymptomsPoor ability to tolerate cold feeling tired constipation weight gain 3 depression anxiety irritability 4 ComplicationsDuring pregnancy can result in cretinism in the baby 5 Usual onset lt 60 years old 3 CausesIodine deficiency Hashimoto s thyroiditis 3 Diagnostic methodBlood tests thyroid stimulating hormone thyroxine 3 Differential diagnosisDepression dementia heart failure chronic fatigue syndrome 6 PreventionSalt iodization 7 TreatmentLevothyroxine 3 Frequency0 3 0 4 USA 8 Worldwide too little iodine in the diet is the most common cause of hypothyroidism 8 9 Hashimoto s thyroiditis is the most common cause of hypothyroidism in countries with sufficient dietary iodine 3 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 3 10 The diagnosis of hypothyroidism when suspected can be confirmed with blood tests measuring thyroid stimulating hormone TSH and thyroxine levels 3 Salt iodization has prevented hypothyroidism in many populations 7 Thyroid hormone replacement with levothyroxine treats hypothyroidism 3 Medical professionals adjust the dose according to symptoms and normalization of the thyroxine and TSH levels 3 Thyroid medication is safe in pregnancy 3 Although an adequate amount of dietary iodine is important too much may worsen specific forms of hypothyroidism 3 Worldwide about one billion people are estimated to be iodine deficient however it is unknown how often this results in hypothyroidism 11 In the United States hypothyroidism occurs in 0 3 0 4 of people 8 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 8 Hypothyroidism is more common in women than in men 3 People over the age of 60 are more commonly affected 3 Dogs are also known to develop hypothyroidism as are cats and horses albeit more rarely 12 The word hypothyroidism is from Greek hypo reduced thyreos shield and eidos form 13 Contents 1 Signs and symptoms 1 1 Myxedema coma 1 2 Pregnancy 1 3 Children 1 4 Related disorders 2 Causes 3 Pathophysiology 4 Diagnosis 4 1 Central 4 2 Overt 4 3 Subclinical 4 4 Pregnancy 5 Prevention 6 Screening 7 Management 7 1 Hormone replacement 7 1 1 Liothyronine 7 1 2 Desiccated animal thyroid 7 2 Subclinical hypothyroidism 7 3 Myxedema coma 7 4 Pregnancy 7 5 Alternative medicine 8 Epidemiology 9 History 10 Other animals 11 References 12 External linksSigns and symptoms editPeople 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 14 15 Hashimoto s thyroiditis may present with the mass effect of a goitre enlarged thyroid gland 14 In middle aged women the symptoms may be mistaken for those of menopause 16 nbsp Symptoms and signs of hypothyroidism 14 Symptoms 14 Signs 14 Fatigue Dry coarse skinFeeling cold Cool extremitiesPoor memory and concentration Myxedema mucopolysaccharide deposits in the skin Constipation dyspepsia 17 Hair lossWeight gain with poor appetite Slow pulse rateShortness of breath Swelling of the limbsHoarse voice Delayed relaxation of tendon reflexesIn females heavy menstrual periods and later light periods Carpal tunnel syndromeAbnormal sensation Pleural effusion ascites pericardial effusionPoor hearingMuscle weaknessDelayed relaxation after testing the ankle jerk reflex is a characteristic sign of hypothyroidism and is associated with the severity of the hormone deficit 8 Myxedema coma edit nbsp Man with myxedema or severe hypothyroidism showing an expressionless face puffiness around the eyes and pallor nbsp Additional 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 18 Pregnancy edit Main article Thyroid disease in women Even mild or subclinical hypothyroidism leads to possible infertility and an increased risk of miscarriage 19 20 Hypothyroidism in early pregnancy even with limited or no symptoms may increase the risk of pre eclampsia offspring with lower intelligence 21 22 23 24 and the risk of infant death around the time of birth 19 20 25 Women are affected by hypothyroidism in 0 3 0 5 of pregnancies 25 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 21 26 27 28 Children edit 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 poor weight gain a hoarse sounding cry feeding difficulties constipation an enlarged tongue umbilical hernia dry skin a decreased body temperature and jaundice 29 A goiter is rare although it may develop later in children who have a thyroid gland that does not produce functioning thyroid hormone 29 A goitre may also develop in children growing up in areas with iodine deficiency 30 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 29 Tooth eruption may be delayed 31 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 29 A goiter may be present with a completely enlarged thyroid gland 29 sometimes only part of the thyroid is enlarged and it can be knobby 32 Related disorders edit 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 33 Causes editHypothyroidism 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 8 34 Primary hypothyroidism is about a thousandfold more common than central hypothyroidism 10 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 8 9 In areas of the world with sufficient dietary iodine hypothyroidism is most commonly caused by the autoimmune disease Hashimoto s thyroiditis chronic autoimmune thyroiditis 8 9 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 8 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 35 There are three different types of estrogens estrone E1 estradiol E2 and estriol E3 with estradiol being the most potent of the three 35 failed verification Women with estrogen dominance have estradiol levels of 115 pg ml on day 3 of their cycle However estrogen dominance is not just about an over abundance of estradiol but is more likely correlated with an imbalance between estradiol and progesterone Women who have too 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 uteri 36 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 37 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 38 This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism 20 40 remain permanently hypothyroid 38 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 8 It may occur as part of autoimmune polyendocrine syndrome type 1 and type 2 8 Iatrogenic hypothyroidism can be surgical a result of thyroidectomy usually for thyroid nodules or cancer or following radioiodine ablation usually for Graves disease Type of hypothyroidism CausesPrimary hypothyroidism 8 Iodine deficiency developing countries autoimmune thyroiditis subacute granulomatous thyroiditis subacute lymphocytic thyroiditis postpartum thyroiditis previous thyroidectomy acute infectious thyroiditis 39 previous radioiodine treatment previous external beam radiotherapy to the neckMedication lithium based mood stabilizers amiodarone interferon alpha tyrosine kinase inhibitors such as sunitinibCentral hypothyroidism 10 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 40 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 edit nbsp 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 41 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 42 Additionally the hormone binds to integrin avb3 on the cell membrane thereby stimulating the sodium hydrogen antiporter and processes such as formation of blood vessels and cell growth 42 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 8 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 34 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 10 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 43 Diagnosis editSee also Thyroid function tests Laboratory testing of thyroid stimulating hormone levels in the blood is considered the best initial test for hypothyroidism a second TSH level is often obtained several weeks later for confirmation 44 Levels may be abnormal in the context of other illnesses and TSH testing in hospitalized people is discouraged unless thyroid dysfunction is strongly suspected 8 as the cause of the acute illness 16 An elevated TSH level indicates that the thyroid gland is not producing enough thyroid hormone and free T4 levels are then often obtained 8 16 32 Measuring T3 is discouraged by the AACE in the assessment for hypothyroidism 8 In England and Wales the National Institute for Health and Care Excellence NICE recommends routine T4 testing in children and T3 testing in both adults and children if central hypothyroidism is suspected and the TSH is low 16 There are a number of symptom rating scales for hypothyroidism they provide a degree of objectivity but have limited use for diagnosis 8 TSH T4 InterpretationNormal Normal Normal thyroid functionElevated Low Overt hypothyroidismNormal low Low Central hypothyroidismElevated Normal Subclinical hypothyroidismMany cases of hypothyroidism are associated with mild elevations in creatine kinase and liver enzymes in the blood They typically return to normal when hypothyroidism has been fully treated 8 Levels of cholesterol low density lipoprotein and lipoprotein a can be elevated 8 the impact of subclinical hypothyroidism on lipid parameters is less well defined 30 Very severe hypothyroidism and myxedema coma are characteristically associated with low sodium levels in the blood together with elevations in antidiuretic hormone as well as acute worsening of kidney function due to a number of causes 18 In most causes however it is unclear if the relationship is causal 45 A diagnosis of hypothyroidism without any lumps or masses felt within the thyroid gland does not require thyroid imaging however if the thyroid feels abnormal diagnostic imaging is then recommended 44 The presence of antibodies against thyroid peroxidase TPO makes it more likely that thyroid nodules are caused by autoimmune thyroiditis but if there is any doubt a needle biopsy may be required 8 Central edit If the TSH level is normal or low and serum free T4 levels are low this is suggestive of central hypothyroidism not enough TSH or TRH secretion by the pituitary gland or hypothalamus There may be other features of hypopituitarism such as menstrual cycle abnormalities and adrenal insufficiency There might also be symptoms of a pituitary mass such as headaches and vision changes Central hypothyroidism should be investigated further to determine the underlying cause 10 44 Overt edit In overt primary hypothyroidism TSH levels are high and T4 and T3 levels are low Overt hypothyroidism may also be diagnosed in those who have a TSH on multiple occasions of greater than 5mIU L appropriate symptoms and only a borderline low T4 46 It may also be diagnosed in those with a TSH of greater than 10mIU L 46 Subclinical edit Subclinical hypothyroidism is a biochemical diagnosis characterized by an elevated serum TSH level but with a normal serum free thyroxine level 47 48 49 The incidence of subclinical hypothyroidism is estimated to be 3 15 and a higher incidence is seen in elderly people females and those with lower iodine levels 47 Subclinical hypothyroidism is most commonly caused by autoimmune thyroid diseases especially Hashimoto s thyroiditis 50 The presentation of subclinical hypothyroidism is variable and classic signs and symptoms of hypothyroidism may not be observed 48 Of people with subclinical hypothyroidism a proportion will develop overt hypothyroidism each year In those with detectable antibodies against thyroid peroxidase TPO this occurs in 4 3 while in those with no detectable antibodies this occurs in 2 6 8 In addition to detectable anti TPO antibodies other risk factors for conversion from subclinical hypothyroidism to overt hypothyroidism include female sex or in those with higher TSH levels or lower level of normal free T4 levels 47 Those with subclinical hypothyroidism and detectable anti TPO antibodies who do not require treatment should have repeat thyroid function tested more frequently e g every 6 months compared with those who do not have antibodies 44 47 Pregnancy edit During pregnancy the thyroid gland must produce 50 more thyroid hormone to provide enough thyroid hormone for the developing fetus and the expectant mother 28 In pregnancy free thyroxine levels may be lower than anticipated due to increased binding to thyroid binding globulin and decreased binding to albumin They should either be corrected for the stage of pregnancy 43 or total thyroxine levels should be used instead for diagnosis 8 TSH values may also be lower than normal particularly in the first trimester and the normal range should be adjusted for the stage of pregnancy 8 43 In pregnancy subclinical hypothyroidism is defined as a TSH between 2 5 and 10 mIU L with a normal thyroxine level while those with TSH above 10 mIU L are considered to be overtly hypothyroid even if the thyroxine level is normal 43 Antibodies against TPO may be important in making decisions about treatment and should therefore be determined in women with abnormal thyroid function tests 8 Determination of TPO antibodies may be considered as part of the assessment of recurrent miscarriage as subtle thyroid dysfunction can be associated with pregnancy loss 8 but this recommendation is not universal 51 and presence of thyroid antibodies may not predict future outcome 52 Prevention edit nbsp A 3 month old infant with untreated congenital hypothyroidism showing myxedematous facies a big tongue and skin mottlingHypothyroidism may be prevented in a population by adding iodine to commonly used foods This public health measure has eliminated endemic childhood hypothyroidism in countries where it was once common In addition to promoting the consumption of iodine rich foods such as dairy and fish many countries with moderate iodine deficiency have implemented universal salt iodization 53 Encouraged by the World Health Organization 54 70 of the world s population across 130 countries are receiving iodized salt In some countries iodized salt is added to bread 53 Despite this iodine deficiency has reappeared in some Western countries as a result of attempts to reduce salt intake 53 Pregnant and breastfeeding women who require 66 more daily iodine than non pregnant women may still not be getting enough iodine 53 55 The World Health Organization recommends a daily intake of 250 µg for pregnant and breastfeeding women 56 As many women will not achieve this from dietary sources alone the American Thyroid Association recommends a 150 µg daily supplement by mouth 43 57 Screening editScreening for hypothyroidism is performed in the newborn period in many countries generally using TSH This has led to the early identification of many cases and thus the prevention of developmental delay 58 It is the most widely used newborn screening test worldwide 59 While TSH based screening will identify the most common causes the addition of T4 testing is required to pick up the rarer central causes of neonatal hypothyroidism 29 If T4 determination is included in the screening done at birth this will identify cases of congenital hypothyroidism of central origin in 1 16 000 to 1 160 000 children Considering that these children usually have other pituitary hormone deficiencies early identification of these cases may prevent complications 10 In adults widespread screening of the general population is a matter of debate Some organizations such as the United States Preventive Services Task Force state that evidence is insufficient to support routine screening 60 while others such as the American Thyroid Association recommend either intermittent testing above a certain age in all sexes or only in women 8 Targeted screening may be appropriate in a number of situations where hypothyroidism is common other autoimmune diseases a strong family history of thyroid disease those who have received radioiodine or other radiation therapy to the neck those who have previously undergone thyroid surgery those with an abnormal thyroid examination those with psychiatric disorders people taking amiodarone or lithium and those with a number of health conditions such as certain heart and skin conditions 8 Yearly thyroid function tests are recommended in people with Down syndrome as they are at higher risk of thyroid disease 61 Guidelines for England and Wales from the National Institute for Health and Care Excellence NICE recommend testing for thyroid disease in people with type 1 diabetes and new onset atrial fibrillation and suggests testing in those with depression or unexplained anxiety all ages in children with abnormal growth or unexplained change in behaviour or school performance 16 On diagnosis of autoimmune thyroid disease NICE also recommends screening for celiac disease 62 Management editHormone replacement edit Most people with hypothyroidism symptoms and confirmed thyroxine deficiency are treated with a synthetic long acting form of thyroxine known as levothyroxine L thyroxine 8 15 In young and otherwise healthy people with overt hypothyroidism a full replacement dose adjusted by weight can be started immediately in the elderly and people with heart disease a lower starting dose is recommended to prevent over supplementation and risk of complications 8 34 16 Lower doses may be sufficient in those with subclinical hypothyroidism while people with central hypothyroidism may require a higher than average dose 8 Blood free thyroxine and TSH levels are monitored to help determine whether the dose is adequate This is done 4 8 weeks after the start of treatment or a change in levothyroxine dose Once the adequate replacement dose has been established the tests can be repeated after 6 and then 12 months unless there is a change in symptoms 8 Normalization of TSH does not mean that other abnormalities associated with hypothyroidism improve entirely such as elevated cholesterol levels 63 In people with central secondary hypothyroidism TSH is not a reliable marker of hormone replacement and decisions are based mainly on the free T4 level 8 10 Levothyroxine is best taken 30 60 minutes before breakfast or four hours after food 8 as certain substances such as food and calcium can inhibit the absorption of levothyroxine 64 There is no direct way of increasing thyroid hormone secretion by the thyroid gland 15 Liothyronine edit Treatment with liothyronine alone has not received enough study to make a recommendation as to its use due to its shorter half life it would need to be taken more often than levothyroxine 8 Adding liothyronine synthetic T3 to levothyroxine has been suggested as a measure to provide better symptom control but this has not been confirmed by studies 9 15 65 In 2007 the British Thyroid Association stated that combined T4 and T3 therapy carried a higher rate of side effects and no benefit over T4 alone 15 66 Similarly American guidelines discourage combination therapy due to a lack of evidence although they acknowledge that some people feel better when receiving combination treatment 8 Guidelines by NICE for England and Wales discourage liothyronine 16 People with hypothyroidism who do not feel well despite optimal levothyroxine dosing may request adjunctive treatment with liothyronine A 2012 guideline from the European Thyroid Association recommends that support should be offered with regards to the chronic nature of the disease and that other causes of the symptoms should be excluded Addition of liothyronine should be regarded as experimental initially only for a trial period of 3 months and in a set ratio to the current dose of levothyroxine 67 The guideline explicitly aims to enhance the safety of this approach and to counter its indiscriminate use 67 Desiccated animal thyroid edit Desiccated thyroid extract is an animal based thyroid gland extract 15 most commonly from pigs It is a combination therapy containing forms of T4 and T3 15 It also contains calcitonin a hormone produced in the thyroid gland involved in the regulation of calcium levels T1 and T2 these are not present in synthetic hormone medication 68 This extract was once a mainstream hypothyroidism treatment but its use today is unsupported by evidence 9 15 British Thyroid Association and American professional guidelines discourage its use 8 66 as does NICE 16 Subclinical hypothyroidism edit There is no evidence of a benefit from treating subclinical hypothyroidism in those who are not pregnant and there are potential risks of overtreatment 69 Untreated subclinical hypothyroidism may be associated with a modest increase in the risk of coronary artery disease when the TSH is over 10 mIU L 69 70 A 2007 review found no benefit of thyroid hormone replacement except for some parameters of lipid profiles and left ventricular function 71 There is no association between subclinical hypothyroidism and an increased risk of bone fractures 72 nor is there a link with cognitive decline 73 American guidelines recommend that treatment should be considered in people with symptoms of hypothyroidism detectable antibodies against thyroid peroxidase a history of heart disease or are at an increased risk for heart disease if the TSH is elevated but below 10 mIU L 8 American guidelines further recommend universal treatment independent of risk factors in those with TSH levels that are markedly elevated above 10 mIU L because of an increased risk of heart failure or death due to cardiovascular disease 8 47 NICE recommends that those with a TSH above 10 mIU L should be treated in the same way as overt hypothyroidism Those with an elevated TSH but below 10 mIU L who have symptoms suggestive of hypothyroidism should have a trial of treatment but with the aim to stopping this if the symptoms persist despite normalisation of the TSH 16 A recent meta analysis however found an increased risk for cardiovascular death in subclinical hypothyroidism 74 Myxedema coma edit Myxedema coma or severe decompensated hypothyroidism usually requires admission to the intensive care close observation and treatment of abnormalities in breathing temperature control blood pressure and sodium levels Mechanical ventilation may be required as well as fluid replacement vasopressor agents careful rewarming and corticosteroids for possible adrenal insufficiency which can occur together with hypothyroidism Careful correction of low sodium levels may be achieved with hypertonic saline solutions or vasopressin receptor antagonists 18 For rapid treatment of the hypothyroidism levothyroxine or liothyronine may be administered intravenously particularly if the level of consciousness is too low to be able to safely swallow medication 18 While administration through a nasogastric tube is possible this may be unsafe and is discouraged 18 Pregnancy edit In women with known hypothyroidism who become pregnant it is recommended that serum TSH levels are closely monitored Levothyroxine should be used to keep TSH levels within the normal range for that trimester The first trimester normal range is below 2 5 mIU L and the second and third trimesters normal range is below 3 0 mIU L 15 43 Treatment should be guided by total rather than free thyroxine or by the free T4 index Similarly to TSH the thyroxine results should be interpreted according to the appropriate reference range for that stage of pregnancy 8 The levothyroxine dose often needs to be increased after pregnancy is confirmed 8 34 43 although this is based on limited evidence and some recommend that it is not always required decisions may need to based on TSH levels 75 Women with anti TPO antibodies who are trying to become pregnant naturally or by assisted means may require thyroid hormone supplementation even if the TSH level is normal This is particularly true if they have had previous miscarriages or have been hypothyroid in the past 8 Supplementary levothyroxine may reduce the risk of preterm birth and possibly miscarriage 76 The recommendation is stronger in pregnant women with subclinical hypothyroidism defined as TSH 2 5 10 mIU L who are anti TPO positive in view of the risk of overt hypothyroidism If a decision is made not to treat close monitoring of the thyroid function every 4 weeks in the first 20 weeks of pregnancy is recommended 8 43 If anti TPO is not positive treatment for subclinical hypothyroidism is not currently recommended 43 It has been suggested that many of the aforementioned recommendations could lead to unnecessary treatment in the sense that the TSH cutoff levels may be too restrictive in some ethnic groups there may be little benefit from treatment of subclinical hypothyroidism in certain cases 75 Alternative medicine edit The effectiveness and safety of using Chinese herbal medicines to treat hypothyroidism is not known 77 Epidemiology editWorldwide about one billion people are estimated to be iodine deficient however it is unknown how often this results in hypothyroidism 11 In large population based studies in Western countries with sufficient dietary iodine 0 3 0 4 of the population have overt hypothyroidism A larger proportion 4 3 8 5 have subclinical hypothyroidism 8 Undiagnosed hypothyroidism is estimated to affect about 4 7 of community derived populations in the US and Europe 78 Of people with subclinical hypothyroidism 80 have a TSH level below the 10 mIU L mark regarded as the threshold for treatment 49 Children with subclinical hypothyroidism often return to normal thyroid function and a small proportion develops overt hypothyroidism as predicted by evolving antibody and TSH levels the presence of celiac disease and the presence of a goitre 79 Women are more likely to develop hypothyroidism than men In population based studies women were seven times more likely than men to have TSH levels above 10 mU L 8 2 4 of people with subclinical hypothyroidism will progress to overt hypothyroidism each year The risk is higher in those with antibodies against thyroid peroxidase 8 49 Subclinical hypothyroidism is estimated to affect approximately 2 of children in adults subclinical hypothyroidism is more common in the elderly and in White people 48 There is a much higher rate of thyroid disorders the most common of which is hypothyroidism in individuals with Down syndrome 29 61 and Turner syndrome 29 Very severe hypothyroidism and myxedema coma are rare with it estimated to occur in 0 22 per million people a year 18 The majority of cases occur in women over 60 years of age although it may happen in all age groups 18 Most hypothyroidism is primary in nature Central secondary hypothyroidism affects 1 20 000 to 1 80 000 of the population or about one out of every thousand people with hypothyroidism 10 History editIn 1811 Bernard Courtois discovered iodine was present in seaweed and iodine intake was linked with goitre size in 1820 by Jean Francois Coindet 80 Gaspard Adolphe Chatin proposed in 1852 that endemic goitre was the result of not enough iodine intake and Eugen Baumann demonstrated iodine in thyroid tissue in 1896 80 The first cases of myxedema were recognized in the mid 19th century the 1870s but its connection to the thyroid was not discovered until the 1880s when myxedema was observed in people following the removal of the thyroid gland thyroidectomy 81 The link was further confirmed in the late 19th century when people and animals who had had their thyroid removed showed improvement in symptoms with transplantation of animal thyroid tissue 9 The severity of myxedema and its associated risk of mortality and complications created interest in discovering effective treatments for hypothyroidism 81 Transplantation of thyroid tissue demonstrated some efficacy but recurrences of hypothyroidism was relatively common and sometimes required multiple repeat transplantations of thyroid tissue 81 In 1891 the English physician George Redmayne Murray introduced subcutaneously injected sheep thyroid extract 82 followed shortly after by an oral formulation 9 83 Purified thyroxine was introduced in 1914 and in the 1930s synthetic thyroxine became available although desiccated animal thyroid extract remained widely used Liothyronine was identified in 1952 9 Early attempts at titrating therapy for hypothyroidism proved difficult After hypothyroidism was found to cause a lower basal metabolic rate this was used as a marker to guide adjustments in therapy in the early 20th century around 1915 81 However a low basal metabolic rate was known to be non specific also present in malnutrition 81 The first laboratory test to be helpful in assessing thyroid status was the serum protein bound iodine which came into use around the 1950s In 1971 the thyroid stimulating hormone TSH radioimmunoassay was developed which was the most specific marker for assessing thyroid status in patients 81 Many people who were being treated based on basal metabolic rate minimizing hypothyroid symptoms or based on serum protein bound iodine were found to have excessive thyroid hormone 81 The following year in 1972 a T3 radioimmunoassay was developed and in 1974 a T4 radioimmunoassay was developed 81 Other animals edit nbsp Characteristic changes in the facial skin of a Labrador Retriever with hypothyroidismIn veterinary practice dogs are the species most commonly affected by hypothyroidism The majority of cases occur as a result of primary hypothyroidism of which two types are recognized lymphocytic thyroiditis which is probably immune driven and leads to destruction and fibrosis of the thyroid gland and idiopathic atrophy which leads to the gradual replacement of the gland by fatty tissue 12 84 There is often lethargy cold intolerance exercise intolerance and weight gain Furthermore skin changes and fertility problems are seen in dogs with hypothyroidism as well as a number of other symptoms 84 The signs of myxedema can be seen in dogs with prominence of skin folds on the forehead and cases of myxedema coma are encountered 12 The diagnosis can be confirmed by blood test as the clinical impression alone may lead to overdiagnosis 12 84 Lymphocytic thyroiditis is associated with detectable antibodies against thyroglobulin although they typically become undetectable in advanced disease 84 Treatment is with thyroid hormone replacement 12 Other species that are less commonly affected include cats and horses as well as other large domestic animals In cats hypothyroidism is usually the result of other medical treatment such as surgery or radiation In young horses congenital hypothyroidism has been reported predominantly in Western Canada and has been linked with the mother s diet 12 References edit hypothyroidism Dictionary com Unabridged Online n d hypothyroidism definition of hypothyroidism in English from the Oxford dictionary OxfordDictionaries com Archived from the original on March 11 2013 Retrieved 2016 01 20 a b c d e f g h i j k l m n o p q Hypothyroidism National Institute of Diabetes and Digestive and Kidney Diseases March 2013 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3 105 14 doi 10 1080 00480169 2011 563729 PMID 21541883 S2CID 29535272 External links editHypothyroidism at Curlie Hypothyroidism information for patients American Thyroid Association Retrieved 2017 03 25 UK Guidelines for the use of thyroid function tests PDF The Association for Clinical Biochemistry British Thyroid Association and British Thyroid Foundation 2006 Retrieved 2013 12 25 Alexander EK Pearce EN Brent GA Brown RS Chen H Dosiou C Grobman WA Laurberg P Lazarus JH Mandel SJ Peeters RP Sullivan S March 2017 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum Thyroid 27 3 315 389 doi 10 1089 thy 2016 0457 PMC 3472679 PMID 28056690 Retrieved from https en wikipedia org w index php title Hypothyroidism amp oldid 1194902702, wikipedia, wiki, book, books, library,

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