Hypothyroidism // is a state in which the thyroid gland does not produce a sufficient amount of the thyroid hormones thyroxine (T4) and triiodothyronine (T3).
Iodine deficiency is often cited as the most common cause of hypothyroidism worldwide but it can be caused by many other factors. It can result from the lack of a thyroid gland or from iodine-131 treatment, and can also be associated with increased stress. Severe hypothyroidism in infants can result in cretinism.
A 2011 study concluded that about 8% of women over 50 and men over 65 in the UK suffer from an under-active thyroid and that as many as 100,000 of these people could benefit from treatment they are currently not receiving.
Hypothyroidism is often classified by association with the indicated organ dysfunction (see below):
||The most common forms include Hashimoto's thyroiditis (an autoimmune disease) and radioiodine therapy for hyperthyroidism.
||Occurs if the pituitary gland does not create enough thyroid-stimulating hormone (TSH) to induce 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. Secondary hypothyroidism accounts for less than 5% or 10% of hypothyroidism cases.
||Results when the hypothalamus fails to produce sufficient thyrotropin-releasing hormone (TRH). TRH prompts the pituitary gland to produce thyroid-stimulating hormone (TSH). Hence may also be termed hypothalamic-pituitary-axis hypothyroidism. It accounts for less than 5% of hypothyroidism cases.
Signs and symptoms
Early hypothyroidism is often asymptomatic and can have very mild symptoms. Subclinical hypothyroidism is a state of normal thyroid hormone levels, thyroxine (T4) and triiodothyronine (T3), with mild elevation of thyrotropin, thyroid-stimulating hormone (TSH). With higher TSH levels and low free T4 levels, symptoms become more readily apparent in clinical (or overt) hypothyroidism.
Hypothyroidism can be associated with the following symptoms:
Subclinical hypothyroidism occurs when thyroid stimulating hormone(TSH) levels are elevated but thyroxine (T4) and triiodothyronine (T3) levels are normal. 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. In subclinical hypothyroidism, TSH is elevated but below the limit representing overt hypothyroidism. The levels of the active hormones will be within the laboratory reference ranges.
Generally subclinical hypothyroidism with TSH under 10mU/l does not require treatment.
Pregnancy and fertility
During pregnancy, there is a substantially increased need of thyroid hormones and a substantial risk that previously unnoticed subclinical or latent hypothyroidism will progress to overt hypothyroidism.
Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, has been estimated to increase the risk of pre-eclampsia with an odds ratio (OR) of 1.7 and the risk of perinatal mortality with an OR of 2.7. In subclinical hypothyroidism, supplementation with levothyroxine results in significantly higher delivery rate, with a pooled relative probability of 2.76.
Even mild or subclinical hypothyroidism is known to adversely affect fertility.
Hypothyroidism is estimated to affect between 3.8-4.6% of the general population. 0.3% of the general American population have overt hypothyroidism, and 4.3% have subclinical hypothyroidism. A 1995 survey in the UK found the mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8–4.5) rising to 4.1/1000 survivors/year (3.3–5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3–1.2). Data from the CDC spanning the years 1999 to 2010 yield similar numbers: hypothyroidism is four times as common among women as among men.
Estimates of subclinical hypothyroidism range between 3% and 8%, increasing with age; the median age of someone with hypothyroidism is 58.
Iodine deficiency is the most common cause of hypothyroidism worldwide. In iodine-replete areas of the world, hypothyroidism is most commonly caused by Hashimoto's thyroiditis, or otherwise as a result of either an absent thyroid gland or a deficiency in stimulating hormones from the hypothalamus or pituitary. Congenital hypothyroidism is a rare cause of hypothyroidism and may result from thyroid agenesis and has an incidence of approximately 1 in 4000 births.
Hypothyroidism can be caused by medications such as lithium-based mood stabilizers, a medication usually used to treat bipolar disorder. In fact, lithium has occasionally been used to treat hyperthyroidism. Other drugs that may produce hypothyroidism include amiodarone, interferon alpha, interleukin-2, rifampicin, sunitinib, and thalidomide. Temporary hypothyroidism can be due to the Wolff-Chaikoff effect. A very high intake of iodine can be used to temporarily treat hyperthyroidism, especially in an emergency situation. Although iodide is a substrate for thyroid hormones, high levels reduce iodide organification in the thyroid gland, decreasing hormone production.
Exposure to radioactive iodine-131 can induce a state of hypothyroidism and this effect is used to medically treat hyperthyroidism. De Quervain's thyroiditis, thought to be viral in origin, is a condition that can transiently cause hyperthyroidism and later progress to hypothyroidism.
Hypothyroidism can result from postpartum thyroiditis up to 9 months after giving birth, characterized by transient hyperthyroidism followed by transient hypothyroidism. The syndrome is seen in 5 to 9% of women. The first phase is typically hyperthyroidism; the thyroid then either returns to normal, or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, 25 to 30% will develop permanent hypothyroidism requiring lifelong thyroxine replacement therapy.
Stress and hypothyroidism
Stress is known to be a significant contributor to thyroid dysfunction; this can be environmental stress as well as lesser-considered homeostatic stress such as fluctuating blood sugar levels and immune problems. Stress's effect on thyroid function can be indirect, through its effects on blood sugar levels (dysglycemia), but it can also have more direct effects. Stress may cause hypothyroidism or reduced thyroid functioning by disrupting the HPA axis which down-regulates thyroid function, reducing the conversion of T4 to T3, weakening the immune system thus promoting autoimmunity, causing thyroid hormone resistance, and resulting in hormonal imbalances. Indeed, excess estrogen in the blood caused by chronic cortisol elevations can result in hypothyroid symptoms by decreasing levels of active T3. Stress also affects thyroid functioning through the sympathetic nervous system. A 1994 study of refugees from East Germany who experienced chronic stress found them to have a very high rate of hypothyroidism or subclinical hypothyroidism, although not all refugees displayed clinical or behavioral symptoms associated with this reduced thyroid functioning. TSH levels correlate positively with physiological stress.
Adrenal insufficiency can also result in hypothyroid symptoms without affecting the thyroid itself.
The only validated test to diagnose primary hypothyroidism, is to measure thyroid-stimulating hormone (TSH) and free thyroxine (T4). However, these levels can be affected by non-thyroidal illnesses.
High levels of TSH indicate that the thyroid is not producing sufficient levels of thyroid hormone (mainly as thyroxine (T4) and smaller amounts of triiodothyronine (T3)). However, measuring just TSH fails to diagnose secondary and tertiary hypothyroidism, thus leading to the following suggested blood testing if the TSH is normal and hypothyroidism is still suspected:
- Free triiodothyronine (fT3)
- Free thyroxine (fT4)
- Total T3
- Total T4
Additionally, the following measurements may be needed:
- Free T3 from 24-hour urine catch
- Antithyroid antibodies – for evidence of autoimmune diseases that may be damaging the thyroid gland
- 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
Hypothyroidism is treated with the levorotatory forms of thyroxine (levothyroxine) (L-T4) and triiodothyronine (liothyronine) (L-T3). Synthroid, produced by Abbott Laboratories, is the brand name counterpart to the generic Levothyroxine. Synthroid is also the most common pill prescribed by doctors that has the synthetic thyroid hormone in it, and it is taken by over 40% of people with hypothyroidism. This medicine can improve symptoms of thyroid deficiency such as slow speech, lack of energy, weight gain, hair loss, dry skin, and feeling cold. It also helps to treat goiter. It is also used to treat some kinds of thyroid cancer along with surgery and other medicines. 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, the generic form of synthroid, is best taken 30–60 minutes before breakfast, as some food can diminish absorption. Calcium can inhibit the absorption of levothryoxine. Compared to water, coffee reduces absorption of levothyroxine by about 30 percent. Some patients might appear to be resistant to levothyroxine, when in fact they do not properly absorb the tablets – a problem which is solved by pulverizing the medication. There are several different treatment protocols in thyroid-replacement therapy:
- T4 only
- This treatment involves supplementation of levothyroxine alone, in a synthetic form. It is currently the standard treatment in mainstream medicine.
- T4 and T3 in combination
- This treatment protocol involves administering both synthetic L-T4 and L-T3 simultaneously in combination.
- Desiccated thyroid extract
- Desiccated thyroid extract is an animal-based thyroid extract, most commonly from a porcine source. It is also a combination therapy, containing natural forms of L-T4 and L-T3, as well as L-T1 and L-T2, which are not present in synthetic hormone medication.
The potential benefit from substituting some T3 for T4 has been investigated, but no conclusive benefit for combination therapy has been shown.
The 2002 Laboratory Medicine Practice Guidelines of the National Academy of Clinical Biochemistry state that during pregnancy, "The L-T4 dose should be increased (usually by 50 mcg/day) to maintain a serum TSH between 0.5 and 2.0 mIU/L and a serum FT4 in the upper third of the normal reference interval." Doctors however often assume that if your TSH is in the "normal range", sometimes defined as high as 5.5 mIu/L, it has no effect on fertility. Healthy pregnant women however have a TSH level of around 1.0 mIU/L.
Whilst previously there was has been some debate on the biochemical and symptomatic point at which to treat with levothyroxine, the typical treatment for overt hypothyroidism, the American Association of Clinical Endocrinologists (ACEE) 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".
There is always the risk of overtreatment and hyperthyroidism. Some studies have suggested that subclinical hypothyroidism does not need to be treated. A 2002 meta-analysis looking into whether subclinical hypothyroidism may increase the risk of cardiovascular disease, as has been previously suggested, found a possible modest increase and suggested further studies be undertaken with coronary-heart disease as an end point "before current recommendations are updated." A 2007 meta-analysis by the Cochrane Collaboration found no benefit of thyroid-hormone replacement except "some parameters of lipid profiles and left-ventricular function."
Consensus American and British opinion since 2008, has been that in general patients with TSH under 10mU/l do not require treatment.
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 still controversial and is rejected by the conventional medical establishment.
Hypothyroidism is also a relatively common disease in domestic dogs, with some specific breeds having a definite predisposition.
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