|Classification and external resources|
Hypothyroidism // is an endocrine disorder in which the thyroid gland produces inadequate quantities of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). The global prevalence of hypothyroidism is estimated to be 2–5% while subclinical hypothyroidism is thought to have a prevalence of 4.0–8.5% worldwide.
Iodine deficiency due to insufficient intake of dietary iodine is the most common cause of hypothyroidism worldwide; in iodine-replete countries, the predominant cause of hypothyroidism is the autoimmune condition Hashimoto's disease. Hypothyroidism has numerous causes such as treatment with radioactive iodine-131, injury to the hypothalamus gland or the anterior pituitary gland, medications, congenital absence or surgical removal of a functioning thyroid gland, and increased stress. Severe hypothyroidism in infants can result in a state of stunted physical and mental development known as cretinism.
Hypothyroidism may be classified by association with the indicated organ dysfunction.1
|Primary||Thyroid gland||Primary hypothyroidism occurs when there is an abnormality intrinsic to the thyroid gland and is most often due to an autoimmune thyroiditis such as Hashimoto's thyroiditis.2|
|Secondary||Pituitary gland||Occurs if pituitary malfunction leads to insufficient production of thyroid-stimulating hormone (TSH), which normally induces the thyroid gland to produce enough thyroxine and triiodothyronine. Although not every case of secondary hypothyroidism has a clear cause, it is usually caused by damage to the pituitary gland, as by a tumor, radiation, or surgery.3 Secondary hypothyroidism accounts for less than 5%4 to 10%5 of hypothyroidism cases.|
|Tertiary||Hypothalamus||Results when the hypothalamus fails to produce sufficient thyrotropin-releasing hormone (TRH). TRH prompts the pituitary gland to produce thyroid-stimulating hormone (TSH); it may also be termed hypothalamic-pituitary-axis hypothyroidism. It accounts for less than 5% of hypothyroidism cases.4|
Hypothyroidism is often asymptomatic and can have very mild symptoms. Numerous signs and symptoms have been associated with hypothyroidism. These signs and symptoms can relate to the underlying pathological cause of the hypothyroidism, a mass effect of a thyroid goiter, or direct effects of having insufficient thyroid hormones. Signs and symptoms may include:67
- Appearance: thin, brittle fingernails; dry, itchy skin; weight gain, swollen eyelids, myxedema, hair loss,8 thinning of the outer third of the eyebrow, dry 'puffy' facial skin, puffy face, hands and feet, enlarged tongue7
- Neurological: depression, rapid thoughts, mood instability, irritability, slow speech and hoarse voice, deepening of the voice due to Reinke's Edema, impaired memory,9 impaired concentration,1 loss of sense of smell, hearing impairment,7 acute psychosis, (myxedema madness) (a rare presentation of hypothyroidism)
- Neuromuscular: depressed reflexes, hypotonia, muscle cramps, muscle weakness,8 joint pain, carpal tunnel syndrome and bilateral paresthesia, difficulty swallowing, shortness of breath with a shallow and slow respiratory pattern
- Gastrointestinal: constipation1
- Constitutional: fatigue,8 sleepiness, cold intolerance, decreased sweating, low basal body temperature
- Cardiovascular: slowed heart rate, decreased blood pressure, elevated serum cholesterol,1 hyponatremia, pleural effusion, pericardial effusion, anemia (most commonly normocytic and normochromic) caused by impaired hemoglobin synthesis (decreased erythropoietin levels), iron deficiency anemia due to impaired intestinal absorption of iron may occur, or a macrocytic anemia may be caused by impaired intestinal folate absorption or Vitamin B12 deficiency from pernicious anemia (sometimes seen with hypothyroidism in polyglandular autoimmune syndrome or in association with autoimmune thyroiditis)1011
- Endocrine: female infertility, menorrhagia, goiter, decreased libido, erectile dysfunction in men,8 hyperprolactinemia, galactorrhea,812 reactive (or post-prandial) hypoglycemia, impaired renal function with decreased glomerular filtration rate
Iodine deficiency is the most common cause of hypothyroidism worldwide.23 In iodine-replete areas of the world, hypothyroidism is most commonly caused by the autoimmune disease Hashimoto's thyroiditis;213 other causes may include an absent thyroid gland or central hypothyroidism due to impaired production of the hypothalamic hormone thyrotropin releasing hormone (TRH) or the anterior pituitary hormone thyroid stimulating hormone (TSH). Central hypothyroidism may occur following injury to these glands from physical trauma, mass effect (compression) by a tumor, autoimmune injury, vascular insufficiency, and myriad other causes.14 Congenital hypothyroidism is a rare cause of hypothyroidism and most commonly results from thyroid dysgenesis15 and has an incidence of approximately 1 in 4000 births.2
Certain medications may cause hypothyroidism such as lithium-based mood stabilizers, amiodarone, interferon alpha, interleukin-2, rifampicin, sunitinib, and thalidomide.23 Temporary hypothyroidism can be due to failure to escape from the Wolff-Chaikoff effect.16 Partial or total removal of the thyroid gland is another known cause of hypothyroidism.17
Exposure to radioactive iodine-131 can induce a state of hypothyroidism and this effect is used medically to treat hyperthyroidism.18 De Quervain's thyroiditis, thought to be viral in origin, is a condition that can transiently cause hyperthyroidism and later progress to hypothyroidism.19
Hypothyroidism can result from postpartum thyroiditis up to nine months after giving birth and is characterized by a period of transient hyperthyroidism followed by transient hypothyroidism. This condition has an incidence of about 5% in the general population.20 Of women who experience hypothyroidism associated with postpartum thyroiditis, 20-40% develop permanent primary hypothyroidism.20
Iodine intake directly affects the levels of the thyroid hormone, triiodothyronine (T3), which is dependent on carbohydrate intake. One hypothesis says that the modern Western human diet is higher in carbohydrates than the paleolithic diet, which leads to an increase in T3 levels. The iodine intake levels required in the modern diet should then increase for the thyroid to continue functioning properly. When a mismatch between the required iodine intake and actual intake occurs, it creates a vulnerability to hypothyroidism.unreliable medical source? 22
The synthesis of thyroid hormones requires sufficient circulating iodine in the presence of thyroid stimulating hormone (TSH). The iodine is taken up into the thyroid gland and incorporated into thyroglobulin molecules. Insufficient iodine, or insufficient TSH, can result in decreased production of thyroid hormones.1
The hypothalamic–pituitary–thyroid axis plays a key role in maintaining thyroid output. Thyrotropin-releasing hormone (TRH) is released from the hypothalamus, which stimulates the production of TSH by the anterior pituitary gland. TSH stimulates the thyroid gland to produce T3 and T4. If these stimulatory hormone signals are not synthesized or are improperly released due to an injured or abnormal hypothalamus or pituitary gland, this can interfere with proper thyroid function.14
Clinical hypothyroidism occurs in approximately 0.3–0.5% of pregnant women.23 During pregnancy, iodine requirements are higher as there is an increased demand for thyroid hormones due to decreased levels of free thyroid hormone secondary to elevated circulating levels of thyroid binding globulin in response to increased estrogen levels.24 During pregnancy, it is recommended that serum TSH levels are monitored and kept within the normal range for each trimester when treated with levothyroxine monotherapy. The first trimester normal range is below 2.5mIU/L and below 3.0mIU/L in the second and third trimesters.7 Subclinical hypothyroidism in early pregnancy may increase the risk of pre-eclampsia, offspring with lower intelligence, and the risk of perinatal mortality.2325 In subclinical hypothyroidism, supplementation with levothyroxine results in a significantly higher delivery rate.26 Even mild or subclinical hypothyroidism has been associated with impaired fertility.25
Laboratory evaluation of thyroid stimulating hormone (TSH) levels in the blood is considered the best initial screening test for hypothyroidism. If an elevated TSH level is detected, this indicates that the thyroid gland is not producing adequate levels of thyroid hormone and subsequently free T4 levels are often obtained.27 However, measuring TSH levels alone fails to diagnose secondary and tertiary hypothyroidism, leading to further suggested blood testing if the TSH level is normal and hypothyroidism is suspected:
- Free triiodothyronine (fT3)
- Free thyroxine (fT4)
- Total T3
- Total T4
Other laboratory tests that may be ordered for the diagnostic workup of hypothyroidism may include:citation needed
- Free T3 from 24-hour urine catch
- Anti-thyroid autoantibodies such as anti-thyroid peroxidase or anti-thyroglobulin antibodies for evidence of autoimmune diseases that may be damaging the thyroid gland27
- Serum cholesterol – which may be elevated in hypothyroidism
- Prolactin – as a widely available test of pituitary function
- Testing for anemia, including ferritin
- Basal body temperature
In primary hypothyroidism, TSH levels are high and T4 and T3 levels are low. TSH usually increases when T4 and T3 levels drop. TSH prompts the thyroid gland to make more hormone. Subclinical hypothyroidism occurs when serum thyroid stimulating hormone (TSH) levels are elevated but serum free thyroxine (T4) are within normal limits.28 In subclinical hypothyroidism, TSH is elevated but below the limit representing overt hypothyroidism. The presentation of subclinical hypothyroidism is quite variable and classic signs and symptoms of hypothyroidism may not be readily observed.28
Hypothyroidism is treated with the levorotatory forms of thyroxine (levothyroxine) (LT4) and triiodothyronine (liothyronine) (LT3). Both synthetic and animal-derived thyroid tablets are available and can be prescribed for patients in need of additional thyroid hormone. Thyroid hormone is taken daily, and doctors can monitor blood levels to help assure proper dosing. Levothyroxine is best taken 30–60 minutes before breakfast, as food can diminish absorption. Calcium can inhibit the absorption of levothryoxine.29 Coffee consumption may reduce absorption of levothyroxine.30
There are several different treatment protocols in thyroid-replacement therapy:
T4 only: Monotherapy with levothyroxine alone in a synthetic form is the current standard therapy for primary and central hypothyroidism.7
Combination LT4 and LT3: This treatment protocol involves administering both synthetic LT4 and LT3.7 Evidence has not demonstrated combination LT4/LT3 therapy to be a more effective treatment for hypothyroidism than LT4 treatment alone and its use was recommended against by the British Thyroid Association in 2007 due to observed side effects and a lack of demonstrated benefit.7
Desiccated thyroid extract: Desiccated thyroid extract is an animal-based thyroid gland extract,7 most commonly from a porcine source. It is also a combination therapy, containing natural forms of LT4 and LT3.7 It contains calcitonin, LT1 and LT2, which are not present in synthetic hormone medication.citation needed This extract was once a mainstream hypothyroidism treatment, but its use today is unsupported by evidence.7
According to the British Royal College of Physicians, subclinical hypothyroidism with TSH under 10mU/l does not require treatment.31
Physicians often assume that if a TSH is in the "normal range", sometimes defined as high as 5.5 mIu/L, it has no effect on fertility.
Compounded slow-release T3 has been suggested for use in combination with T4, which proponents argue will mitigate many of the symptoms of functional hypothyroidism and improve quality of life; this is controversial and is rejected by the conventional medical establishment.34
There is always the risk of overtreatment and hyperthyroidism. A 2002 meta-analysis looking into whether subclinical hypothyroidism may increase the risk of cardiovascular disease found a possible modest increase and suggested further studies be undertaken with coronary heart disease as an end point "before current recommendations are updated".35 A 2007 meta-analysis by the Cochrane Collaboration found no benefit of thyroid-hormone replacement except for "some parameters of lipid profiles and left-ventricular function".36
Consensus American and British opinion since 2008, has been that in general patients with TSH under 10mU/l do not require treatment.3137 For treatment for overt hypothyroidism, the American Association of Clinical Endocrinologists (AACE) has stated that "the upper limit of TSH should remain at 4.5 mIU/L, rather than 3.0–3.5 as some other organizations have suggested".37
Hypothyroidism is estimated to affect 2.0–5.0% of the global population; subclinical hypothyroidism is estimated to have a prevalence of 4.0–8.5%.1038 The incidence of hypothyroidism is approximately seven times greater in women than in men.11 Subclinical hypothyroidism is estimated to affect approximately 2% of children; in the adult population subclinical hypothyroidism prevalence is higher in women, the elderly, and in Caucasians.28 There is a higher prevalence of thyroid disorders, the most common of which is hypothyroidism, in individuals with Down syndrome.39
Hypothyroidism is relatively common in domestic dogs.40
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- ATA 2013, p. 6
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- ATA 2013, p. 4
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- Erdogan M, Kosenli A, Ganidagli S, Kulaksizoglu M (2012). "Characteristics of anemia in subclinical and overt hypothyroid patients". Endocr J 59 (3): 213–20. PMID 22200582.
- Mistry N, Wass J, Turner MR (June 2009). "When to consider thyroid dysfunction in the neurology clinic". Practical Neurology 9 (3): 145–56. doi:10.1136/jnnp.2008.167163. PMID 19448057.
- Huang W, Molitch ME (June 2012). "Evaluation and management of galactorrhea". Am Family Physician 85 (11): 1073–80. PMID 22962879.
- Gaberšček S, Zaletel K (September 2011). "Thyroid physiology and autoimmunity in pregnancy and after delivery". Expert Rev Clin Immunol 7 (5): 697–706; quiz 707. doi:10.1586/eci.11.42. PMID 21895480.
- Persani L (September 2012). "Clinical review: Central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges". J. Clin. Endocrinol. Metab. 97 (9): 3068–78. doi:10.1210/jc.2012-1616. PMID 22851492.
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- Stagnaro-Green, A (February 2012). "Approach to the patient with postpartum thyroiditis". J Clin Endocrinol Metab 97 (2): 334–42. PMID 22312089.
- Klecha AJ, Barreiro Arcos ML, Frick L, Genaro AM, Cremaschi G (2008). "Immune-endocrine interactions in autoimmune thyroid diseases". Neuroimmunomodulation 15 (1): 68–75. doi:10.1159/000135626. PMID 18667802.
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