<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hyperthyroidism and can you explain it in depth? [/INST] Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism.  It is noted that thyrotoxicosis is related to hyper-kinetic movement disorders including chorea and myoclonus. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature and often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.Graves disease is the cause of about 50% to 80% of the cases of hyperthyroidism in the United States. Other causes include multinodular goiter, toxic adenoma, inflammation of the thyroid, eating too much iodine, and too much synthetic thyroid hormone. A less common cause is a pituitary adenoma. The diagnosis may be suspected based on signs and symptoms and then confirmed with blood tests. Typically blood tests show a low thyroid stimulating hormone (TSH) and raised T3 or T4. Radioiodine uptake by the thyroid, thyroid scan, and TSI antibodies may help determine the cause.Treatment depends partly on the cause and severity of disease. There are three main treatment options: radioiodine therapy, medications, and thyroid surgery. Radioiodine therapy involves taking iodine-131 by mouth which is then concentrated in and destroys the thyroid over weeks to months. The resulting hypothyroidism is treated with synthetic thyroid hormone. Medications such as beta blockers may control the symptoms, and anti-thyroid medications such as methimazole may temporarily help people while other treatments are having an effect. Surgery to remove the thyroid is another option. This may be used in those with very large thyroids or when cancer is a concern. In the United States hyperthyroidism affects about 1.2% of the population. It occurs between two and ten times more often in women. Onset is commonly between 20 and 50 years of age. Overall the disease is more common in those over the age of 60 years.

Signs and symptoms
Hyperthyroidism may be asymptomatic or present with significant symptoms. Some of the symptoms of hyperthyroidism include nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety, trouble sleeping, thinning of the skin, fine brittle hair, and muscular weakness—especially in the upper arms and thighs. More frequent bowel movements may occur, and diarrhea is common. Weight loss, sometimes significant, may occur despite a good appetite (though 10% of people with a hyperactive thyroid experience weight gain), vomiting may occur, and, for women, menstrual flow may lighten and menstrual periods may occur less often, or with longer cycles than usual.Thyroid hormone is critical to normal function of cells. In excess, it both overstimulates metabolism and disrupts the normal functioning of sympathetic nervous system, causing "speeding up" of various body systems and symptoms resembling an overdose of epinephrine (adrenaline). These include fast heartbeat and symptoms of palpitations, nervous system tremor such as of the hands and anxiety symptoms, digestive system hypermotility, unintended weight loss, and, in lipid panel blood tests, a lower and sometimes unusually low serum cholesterol.Major clinical signs of hyperthyroidism include weight loss (often accompanied by an increased appetite), anxiety, heat intolerance, hair loss (especially of the outer third of the eyebrows), muscle aches, weakness, fatigue, hyperactivity, irritability, high blood sugar, excessive urination, excessive thirst, delirium, tremor, pretibial myxedema (in Graves disease), emotional lability, and sweating.  Panic attacks, inability to concentrate, and memory problems may also occur. Psychosis and paranoia, common during thyroid storm, are rare with milder hyperthyroidism. Many persons will experience complete remission of symptoms 1 to 2 months after a euthyroid state is obtained, with a marked reduction in anxiety, sense of exhaustion, irritability, and depression. Some individuals may have an increased rate of anxiety or persistence of affective and cognitive symptoms for several months to up to 10 years after a euthyroid state is established. In addition, those with hyperthyroidism may present with a variety of physical symptoms such as palpitations and abnormal heart rhythms (the notable ones being atrial fibrillation), shortness of breath (dyspnea), loss of libido, amenorrhea, nausea, vomiting, diarrhea, gynecomastia and feminization. Long term untreated hyperthyroidism can lead to osteoporosis. These classical symptoms may not be present often in the elderly.Neurological manifestations can include tremors, chorea, myopathy, and in some susceptible individuals (in particular of Asian descent) periodic paralysis. An association between thyroid disease and myasthenia gravis has been recognized. Thyroid disease, in this condition, is autoimmune in nature and approximately 5% of people with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is not well understood.In Graves disease, ophthalmopathy may cause the eyes to look enlarged because the eye muscles swell and push the eye forward. Sometimes, one or both eyes may bulge. Some have swelling of the front of the neck from an enlarged thyroid gland (a goiter).Minor ocular (eye) signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare"), extraocular muscle weakness, and lid-lag. In hyperthyroid stare (Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superior corneoscleral limbus, where the "white" of the eye begins at the upper border of the iris). Extraocular muscle weakness may present with double vision. In lid-lag (von Graefes sign), when the person tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism.Neither of these ocular signs should be confused with exophthalmos (protrusion of the eyeball), which occurs specifically and uniquely in hyperthyroidism caused by Graves disease (note that not all exophthalmos is caused by Graves disease, but when present with hyperthyroidism is diagnostic of Graves disease). This forward protrusion of the eyes is due to immune-mediated inflammation in the retro-orbital (eye socket) fat. Exophthalmos, when present, may exacerbate hyperthyroid lid-lag and stare.

Thyroid storm
Thyroid storm is a severe form of thyrotoxicosis characterized by rapid and often irregular heart beat, high temperature, vomiting, diarrhea, and mental agitation. Symptoms may not be typical in the young, old, or pregnant. It usually occurs due to untreated hyperthyroidism and can be provoked by infections. It is a medical emergency and requires hospital care to control the symptoms rapidly. Even with treatment, death occurs in 20% to 50% of cases.

Hypothyroidism
Hyperthyroidism due to certain types of thyroiditis can eventually lead to hypothyroidism (a lack of thyroid hormone), as the thyroid gland is damaged. Also, radioiodine treatment of Graves disease often eventually leads to hypothyroidism. Such hypothyroidism may be diagnosed with thyroid hormone testing and treated by oral thyroid hormone supplementation.

Causes
There are several causes of hyperthyroidism. Most often, the entire gland is overproducing thyroid hormone. Less commonly, a single nodule is responsible for the excess hormone secretion, called a "hot" nodule. Thyroiditis (inflammation of the thyroid) can also cause hyperthyroidism. Functional thyroid tissue producing an excess of thyroid hormone occurs in a number of clinical conditions.
The major causes in humans are:

Graves disease. An autoimmune disease (usually, the most common cause with 50–80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981)). Thought to be due to varying levels of iodine in the diet. It is eight times more common in females than males and often occurs in young females, around 20 – 40 years of age.
Toxic thyroid adenoma (the most common cause in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country)
Toxic multinodular goiterHigh blood levels of thyroid hormones (most accurately termed hyperthyroxinemia) can occur for a number of other reasons:

Inflammation of the thyroid is called thyroiditis. There are several different kinds of thyroiditis including Hashimotos thyroiditis (Hypothyroidism immune-mediated), and subacute thyroiditis (de Quervains). These may be initially associated with secretion of excess thyroid hormone but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism.
Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of eating ground beef or pork contaminated with thyroid tissue, and thus thyroid hormones (termed hamburger thyrotoxicosis or alimentary thyrotoxicosis). Pharmacy compounding errors may also be a cause.
Amiodarone, an antiarrhythmic drug, is structurally similar to thyroxine and may cause either under-or overactivity of the thyroid.
Postpartum thyroiditis (PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment.
A struma ovarii is a rare form of monodermal teratoma that contains mostly thyroid tissue, which leads to hyperthyroidism.
Excess iodine consumption notably from algae such as kelp.Thyrotoxicosis can also occur after taking too much thyroid hormone in the form of supplements, such as levothyroxine (a phenomenon known as exogenous thyrotoxicosis, alimentary thyrotoxicosis, or occult factitial thyrotoxicosis).Hypersecretion of thyroid stimulating hormone (TSH), which in turn is almost always caused by a pituitary adenoma, accounts for much less than 1 percent of hyperthyroidism cases.

Diagnosis
Measuring the level of thyroid-stimulating hormone (TSH), produced by the pituitary gland (which in turn is also regulated by the hypothalamuss TSH Releasing Hormone) in the blood is typically the initial test for suspected hyperthyroidism. A low TSH level typically indicates that the pituitary gland is being inhibited or "instructed" by the brain to cut back on stimulating the thyroid gland, having sensed increased levels of T4 and/or T3 in the blood. In rare circumstances, a low TSH indicates primary failure of the pituitary, or temporary inhibition of the pituitary due to another illness (euthyroid sick syndrome) and so checking the T4 and T3 is still clinically useful.Measuring specific antibodies, such as anti-TSH-receptor antibodies in Graves disease, or anti-thyroid peroxidase in Hashimotos thyroiditis—a common cause of hypothyroidism—may also contribute to the diagnosis. The diagnosis of hyperthyroidism is confirmed by blood tests that show a decreased thyroid-stimulating hormone (TSH) level and elevated T4 and T3 levels. TSH is a hormone made by the pituitary gland in the brain that tells the thyroid gland how much hormone to make. When there is too much thyroid hormone, the TSH will be low. A radioactive iodine uptake test and thyroid scan together characterizes or enables radiologists and doctors to determine the cause of hyperthyroidism. The uptake test uses radioactive iodine injected or taken orally on an empty stomach to measure the amount of iodine absorbed by the thyroid gland. Persons with hyperthyroidism absorb much more iodine than healthy persons which includes radioactive iodine which is easy to measure.  A thyroid scan producing images is typically conducted in connection with the uptake test to allow visual examination of the over-functioning gland.Thyroid scintigraphy is a useful test to characterize (distinguish between causes of) hyperthyroidism, and this entity from thyroiditis. This test procedure typically involves two tests performed in connection with each other: an iodine uptake test and a scan (imaging) with a gamma camera. The uptake test involves administering a dose of radioactive iodine (radioiodine), traditionally iodine-131 (131I), and more recently iodine-123 (123I). Iodine-123 may be the preferred radionuclide in some clinics due to its more favorable radiation dosimetry (i.e. less radiation dose to the person per unit administered radioactivity) and a gamma photon energy more amenable to imaging with the gamma camera. For the imaging scan, I-123 is considered an almost ideal isotope of iodine for imaging thyroid tissue and thyroid cancer metastasis.Typical administration involves a pill or liquid containing sodium iodide (NaI) taken orally, which contains a small amount of iodine-131, amounting to perhaps less than a grain of salt. A 2-hour fast of no food prior to and for 1 hour after ingesting the pill is required. This low dose of radioiodine is typically tolerated by individuals otherwise allergic to iodine (such as those unable to tolerate contrast mediums containing larger doses of iodine such as used in CT scan, intravenous pyelogram (IVP), and similar imaging diagnostic procedures). Excess radioiodine that does not get absorbed into the thyroid gland is eliminated by the body in urine. Some people with hyperthyroidism may experience a slight allergic reaction to the diagnostic radioiodine and may be given an antihistamine.The person returns 24 hours later to have the level of radioiodine "uptake" (absorbed by the thyroid gland) measured by a device with a metal bar placed against the neck, which measures the radioactivity emitting from the thyroid. This test takes about 4 minutes while the uptake % (i.e., percentage) is accumulated (calculated) by the machine software. A scan is also performed, wherein images (typically a center, left and right angle) are taken of the contrasted thyroid gland with a gamma camera; a radiologist will read and prepare a report indicating the uptake % and comments after examining the images. People with hyperthyroid will typically "take up" higher than normal levels of radioiodine. Normal ranges for RAI uptake are from 10 to 30%.
In addition to testing the TSH levels, many doctors test for T3, Free T3, T4, and/or Free T4 for more detailed results. Free T4 is unbound to any protein in the blood. Adult limits for these hormones are: TSH (units): 0.45 – 4.50 uIU/mL; T4 Free/Direct (nanograms): 0.82 – 1.77 ng/dl; and T3 (nanograms): 71 – 180 ng/dl. Persons with hyperthyroidism can easily exhibit levels many times these upper limits for T4 and/or T3. See a complete table of normal range limits for thyroid function at the thyroid gland article.
In hyperthyroidism CK-MB (Creatine kinase) is usually elevated.

Subclinical
In overt primary hyperthyroidism, TSH levels are low and T4 and T3 levels are high. Subclinical hyperthyroidism is a milder form of hyperthyroidism characterized by low or undetectable serum TSH level, but with a normal serum free thyroxine level. Although the evidence for doing so is not definitive, treatment of elderly persons having subclinical hyperthyroidism could reduce the number of cases of atrial fibrillation. There is also an increased risk of bone fractures (by 42%) in people with subclinical hyperthyroidism; there is insufficient evidence to say whether treatment with antithyroid medications would reduce that risk.A 2022 meta-analysis found subclinical hyperthyroidism to be associated with cardiovascular death.

Screening
In those without symptoms who are not pregnant there is little evidence for or against screening.

Treatment
Antithyroid drugs
Thyrostatics (antithyroid drugs) are drugs that inhibit the production of thyroid hormones, such as carbimazole (used in the UK) and methimazole (used in the US, Germany and Russia), and propylthiouracil. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase and, thus, the formation of tetraiodothyronine (T4). Propylthiouracil also works outside the thyroid gland, preventing the conversion of (mostly inactive) T4 to the active form T3. Because thyroid tissue usually contains a substantial reserve of thyroid hormone, thyrostatics can take weeks to become effective and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results.A very high dose is often needed early in treatment, but, if too high a dose is used persistently, people can develop symptoms of hypothyroidism. This titrating of the dose is difficult to do accurately, and so sometimes a "block and replace" attitude is taken. In block and replace treatments thyrostatics are taken in sufficient quantities to completely block thyroid hormones, and the person treated as though they have complete hypothyroidism.

Beta-blockers
Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety are mediated by increases in beta-adrenergic receptors on cell surfaces. Beta blockers, typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety. Thus, a person with hyperthyroidism can often obtain immediate temporary relief until the hyperthyroidism can be characterized with the Radioiodine test noted above and more permanent treatment take place. Note that these drugs do not treat hyperthyroidism or any of its long-term effects if left untreated, but, rather, they treat or reduce only symptoms of the condition.Some minimal effect on thyroid hormone production however also comes with propranolol—which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremor, palpitations, anxiety, and heat intolerance. D-propranolol inhibits thyroxine deiodinase, thereby blocking the conversion of T4 to T3, providing some though minimal therapeutic effect. Other beta-blockers are used to treat only the symptoms associated with hyperthyroidism. Propranolol in the UK, and metoprolol in the US, are most frequently used to augment treatment for people with hyperthyroid .

Diet
People with autoimmune hyperthyroidism (such as in Graves disease) should not eat foods high in iodine, such as edible seaweed and kelps.From a public health perspective, the general introduction of iodized salt in the United States in 1924 resulted in lower disease, goiters, as well as improving the lives of children whose mothers would not have eaten enough iodine during pregnancy which would have lowered the IQs of their children.

Surgery
Surgery (thyroidectomy to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing the parathyroid glands, and of cutting the recurrent laryngeal nerve, making swallowing difficult, and even simply generalized staphylococcal infection as with any major surgery. Some people with Graves may opt for surgical intervention. This includes those that cannot tolerate medicines for one reason or another, people that are allergic to iodine, or people that refuse radioiodine.If people have toxic nodules treatments typically include either removal or injection of the nodule with alcohol.

Radioiodine
In iodine-131 (radioiodine) radioisotope therapy, which was first pioneered by Dr. Saul Hertz, radioactive iodine-131 is given orally (either by pill or liquid) on a one-time basis, to severely restrict, or altogether destroy the function of a hyperactive thyroid gland. This isotope of radioactive iodine used for ablative treatment is more potent than diagnostic radioiodine (usually iodine-123 or a very low amount of iodine-131), which has a biological half-life from 8–13 hours. Iodine-131, which also emits beta particles that are far more damaging to tissues at short range, has a half-life of approximately 8 days.  People not responding sufficiently to the first dose are sometimes given an additional radioiodine treatment, at a larger dose. Iodine-131 in this treatment is picked up by the active cells in the thyroid and destroys them, rendering the thyroid gland mostly or completely inactive.Since iodine is picked up more readily (though not exclusively) by thyroid cells, and (more important) is picked up even more readily by over-active thyroid cells, the destruction is local, and there are no widespread side effects with this therapy. Radioiodine ablation has been used for over 50 years, and the only major reasons for not using it are pregnancy and breastfeeding (breast tissue also picks up and concentrates iodine). Once the thyroid function is reduced, replacement hormone therapy (levothyroxine) taken orally each day replaces the thyroid hormone that is normally produced by the body.There is extensive experience, over many years, of the use of radioiodine in the treatment of thyroid overactivity and this experience does not indicate any increased risk of thyroid cancer following treatment. However, a study from 2007 has reported an increased number of cancer cases after radioiodine treatment for hyperthyroidism.The principal advantage of radioiodine treatment for hyperthyroidism is that it tends to have a much higher success rate than medications. Depending on the dose of radioiodine chosen, and the disease under treatment (Graves vs. toxic goiter, vs. hot nodule etc.), the success rate in achieving definitive resolution of the hyperthyroidism may vary from 75 to 100%. A major expected side-effect of radioiodine in people with Graves disease is the development of lifelong hypothyroidism, requiring daily treatment with thyroid hormone. On occasion, some people may require more than one radioactive treatment, depending on the type of disease present, the size of the thyroid, and the initial dose administered.People with Graves disease manifesting moderate or severe Graves ophthalmopathy are cautioned against radioactive iodine-131 treatment, since it has been shown to exacerbate existing thyroid eye disease. People with mild or no ophthalmic symptoms can mitigate their risk with a concurrent six-week course of prednisone. The mechanisms proposed for this side effect involve a TSH receptor common to both thyrocytes and retro-orbital tissue.As radioactive iodine treatment results in the destruction of thyroid tissue, there is often a transient period of several days to weeks when the symptoms of hyperthyroidism may actually worsen following radioactive iodine therapy. In general, this happens as a result of thyroid hormones being released into the blood following the radioactive iodine-mediated destruction of thyroid cells that contain thyroid hormone. In some people, treatment with medications such as beta blockers (propranolol, atenolol, etc.) may be useful during this period of time. Most people do not experience any difficulty after the radioactive iodine treatment, usually given as a small pill. On occasion, neck tenderness or a sore throat may become apparent after a few days, if moderate inflammation in the thyroid develops and produces discomfort in the neck or throat area. This is usually transient, and not associated with a fever, etc.It is recommended that breastfeeding be stopped at least six weeks before radioactive iodine treatment and that it not be resumed, although it can be done in future pregnancies. It also shouldnt be done during pregnancy, and pregnancy should be put off until at least 6–12 months after treatment.A common outcome following radioiodine is a swing from hyperthyroidism to the easily treatable hypothyroidism, which occurs in 78% of those treated for Graves thyrotoxicosis and in 40% of those with toxic multinodular goiter or solitary toxic adenoma. Use of higher doses of radioiodine reduces the number of cases of treatment failure, with penalty for higher response to treatment consisting mostly of higher rates of eventual hypothyroidism which requires hormone treatment for life.There is increased sensitivity to radioiodine therapy in thyroids appearing on ultrasound scans as more uniform (hypoechogenic), due to densely packed large cells, with 81% later becoming hypothyroid, compared to just 37% in those with more normal scan appearances (normoechogenic).

Thyroid storm
Thyroid storm presents with extreme symptoms of hyperthyroidism.  It is treated aggressively with resuscitation measures along with a combination of the above modalities including: an intravenous beta blockers such as propranolol, followed by a thioamide such as methimazole, an iodinated radiocontrast agent or an iodine solution if the radiocontrast agent is not available, and an intravenous steroid such as hydrocortisone.

Alternative medicine
In countries such as China, herbs used alone or with antithyroid medications are used to treat hyperthyroidism. Very low quality evidence suggests that traditional Chinese herbal medications may be beneficial when taken along with routine hyperthyroid medications, however, there is no reliable evidence to determine the effectiveness of Chinese herbal medications for treating hyperthyroidism.

Epidemiology
In the United States hyperthyroidism affects about 1.2% of the population. About half of these cases have obvious symptoms while the other half do not. It occurs between two and ten times more often in women. The disease is more common in those over the age of 60 years.Subclinical hyperthyroidism modestly increases the risk of cognitive impairment and dementia.

History
Caleb Hillier Parry first made the association between the goiter and protrusion of the eyes in 1786, however, did not publish his findings until 1825. In 1835, Irish doctor Robert James Graves discovered a link between the protrusion of the eyes and goiter, giving his name to the autoimmune disease now known as Graves Disease.

Pregnancy
Recognizing and evaluating hyperthyroidism in pregnancy is a diagnostic challenge. Thyroid hormones are naturally elevated during pregnancy. Thyroid function generally normalizes in by the second trimester without treatment. Hyperthyroidism must also be distinguished from gestational transient thyrotoxicosis; as it can increase the risk of complications for mother and child. Such risks include pregnancy-related hypertension, pregnancy loss, low-birth weight, still birth and behavioral disorders later in the childs life. Nonetheless, high maternal FT4 levels during pregnancy have been associated with impaired brain developmental outcomes of the offspring and this was independent of for example hCG levels.

Other animals
Cats
Hyperthyroidism is one of the most common endocrine conditions affecting older domesticated housecats. In the United States, up to 10% of cats over ten years old have hyperthyroidism. The disease has become significantly more common since the first reports of feline hyperthyroidism in the 1970s. The most common cause of hyperthyroidism in cats is the presence of benign tumors called adenomas. 98% of cases are caused by the presence of an adenoma, but the reason these cats develop such tumors continues to be studied.
The most common presenting symptoms are: rapid weight loss, tachycardia (rapid heart rate), vomiting, diarrhea, increased consumption of fluids (polydipsia), increased appetite (polyphagia), and increased urine production (polyuria). Other symptoms include hyperactivity, possible aggression, an unkempt appearance, and large, thick claws. Heart murmurs and a gallop rhythm can develop due to secondary hypertrophic cardiomyopathy.  About 70% of affected cats also have enlarged thyroid glands (goiter). 10% of cats exhibit "apathetic hyperthyroidism", which is characterized by anorexia and lethargy.The same three treatments used with humans are also options in treating feline hyperthyroidism (surgery, radioiodine treatment, and anti-thyroid drugs). There is also a special low iodine diet available that will control the symptoms providing no other food is fed; Hills y/d formula, when given exclusively, decreases T4 production by limiting the amount of iodine needed for thyroid hormone production. It is the only available commercial diet that focuses on managing feline hyperthyroidism. Medical and dietary management using methimazole and Hills y/d cat food will give hyperthyroid cats an average of 2 years before dying due to secondary conditions such as heart and kidney failure. Drugs used to help manage the symptoms of hyperthyroidism are methimazole and carbimazole. Drug therapy is the least expensive option, even though the drug must be administered daily for the remainder of the cats life. Carbimazole is only available as a once daily tablet. Methimazole is available as an oral solution, a tablet, and compounded as a topical gel that is applied using a finger cot to the hairless skin inside a cats ear. Many cat owners find this gel a good option for cats that dont like being given pills.
Radioiodine treatment, however, is not available in all areas, as this treatment requires nuclear radiological expertise and facilities that not only board the cat, but are specially equipped to manage the cats urine, sweat, saliva, and stool, which are radioactive for several days after the treatment, usually for a total of 3 weeks (the cat spends the first week in total isolation and the next two weeks in close confinement). In the United States, the guidelines for radiation levels vary from state to state; some states such as Massachusetts allow hospitalization for as little as two days before the animal is sent home with care instructions.

Dogs
Hyperthyroidism is much less common in dogs compared to cats. Hyperthyroidism may be caused by a thyroid tumor. This may be a thyroid carcinoma. About 90% of carcinomas are very aggressive; they invade the surrounding tissues and metastasize (spread) to other tissues, particularly the lungs </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Kuru and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Mitochondrial disease and can you explain it in depth? [/INST] Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of food molecules into the ATP that powers most cell functions.
Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function. A subclass of these diseases that have neuromuscular symptoms are known as mitochondrial myopathies.

Types
Examples of mitochondrial diseases include:

Mitochondrial myopathy
Diabetes mellitus and deafness (DAD)
this combination at an early age can be due to mitochondrial disease
Diabetes mellitus and deafness can be found together for other reasons
Lebers hereditary optic neuropathy (LHON)
visual loss beginning in young adulthood
eye disorder characterized by progressive loss of central vision due to degeneration of the optic nerves and retina
affects 1 in 50,000 people in Finland
Leigh syndrome, subacute necrotizing encephalomyelopathyafter normal development the disease usually begins late in the first year of life, although onset may occur in adulthood
a rapid decline in function occurs and is marked by seizures, altered states of consciousness, dementia, ventilatory failure
Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
progressive symptoms as described in the acronym
dementia
Myoneurogenic gastrointestinal encephalopathy (MNGIE)
gastrointestinal pseudo-obstruction
neuropathy
MERRF syndrome
progressive myoclonic epilepsy
"Ragged Red Fibers" are clumps of diseased mitochondria that accumulate in the subsarcolemmal region of the muscle fiber and appear when muscle is stained with modified Gömöri trichrome stain
short stature
hearing loss
lactic acidosis
exercise intolerance
MELAS syndrome
Mitochondrial DNA depletion syndromeConditions such as Friedreichs ataxia can affect the mitochondria but are not associated with mitochondrial proteins.

Presentation
Associated conditions
Acquired conditions in which mitochondrial dysfunction has been involved are:

diabetes
Huntingtons disease
cancer
Alzheimers disease,
Parkinsons disease
bipolar disorder, schizophrenia, aging and senescence, anxiety disorders
cardiovascular disease
sarcopenia
chronic fatigue syndromeThe body, and each mutation, is modulated by other genome variants; the mutation that in one individual may cause liver disease might in another person cause a brain disorder. The severity of the specific defect may also be great or small. Some defects include exercise intolerance. Defects often affect the operation of the mitochondria and multiple tissues more severely, leading to multi-system diseases.It has also been reported that drug tolerant cancer cells have an increased number and size of mitochondria, which suggested an increase in mitochondrial biogenesis. Interestingly, a recent study in Nature Nanotechnology has reported that cancer cells can hijack the mitochondria from immune cells via physical tunneling nanotubes.As a rule, mitochondrial diseases are worse when the defective mitochondria are present in the muscles, cerebrum, or nerves, because these cells use more energy than most other cells in the body.
Although mitochondrial diseases vary greatly in presentation from person to person, several major clinical categories of these conditions have been defined, based on the most common phenotypic features, symptoms, and signs associated with the particular mutations that tend to cause them.An outstanding question and area of research is whether ATP depletion or reactive oxygen species are in fact responsible for the observed phenotypic consequences.Cerebellar atrophy or hypoplasia has sometimes been reported to be associated.

Causes
Mitochondrial disorders may be caused by mutations (acquired or inherited), in mitochondrial DNA (mtDNA), or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondrial dysfunction due to adverse effects of drugs, infections, or other environmental causes. Oxalate may enter cells where it is known to cause mitochondrial dysfunction.

Nuclear DNA has two copies per cell (except for sperm and egg cells), one copy being inherited from the father and the other from the mother. Mitochondrial DNA, however, is inherited from the mother only (with some exceptions) and each mitochondrion typically contains between 2 and 10 mtDNA copies. During cell division the mitochondria segregate randomly between the two new cells. Those mitochondria make more copies, normally reaching 500 mitochondria per cell. As mtDNA is copied when mitochondria proliferate, they can accumulate random mutations, a phenomenon called heteroplasmy. If only a few of the mtDNA copies inherited from the mother are defective, mitochondrial division may cause most of the defective copies to end up in just one of the new mitochondria (for more detailed inheritance patterns, see human mitochondrial genetics). Mitochondrial disease may become clinically apparent once the number of affected mitochondria reaches a certain level; this phenomenon is called "threshold expression".
Mitochondria possess many of the same DNA repair pathways as nuclei do—but not all of them; therefore, mutations occur more frequently in mitochondrial DNA than in nuclear DNA (see Mutation rate). This means that mitochondrial DNA disorders may occur spontaneously and relatively often. Defects in enzymes that control mitochondrial DNA replication (all of which are encoded for by genes in the nuclear DNA) may also cause mitochondrial DNA mutations.
Most mitochondrial function and biogenesis is controlled by nuclear DNA. Human mitochondrial DNA encodes 13 proteins of the respiratory chain, while most of the estimated 1,500 proteins and components targeted to mitochondria are nuclear-encoded. Defects in nuclear-encoded mitochondrial genes are associated with hundreds of clinical disease phenotypes including anemia, dementia, hypertension, lymphoma, retinopathy, seizures, and neurodevelopmental disorders.A study by Yale University researchers (published in the February 12, 2004, issue of the New England Journal of Medicine) explored the role of mitochondria in insulin resistance among the offspring of patients with type 2 diabetes.
Other studies have shown that the mechanism may involve the interruption of the mitochondrial signaling process in body cells (intramyocellular lipids). A study conducted at the Pennington Biomedical Research Center in Baton Rouge, Louisiana showed that this, in turn, partially disables the genes that produce mitochondria.

Mechanisms
The effective overall energy unit for the available body energy is referred to as the daily glycogen generation capacity, and is used to compare the mitochondrial output of affected or chronically glycogen-depleted individuals to healthy individuals. This value is slow to change in a given individual, as it takes between 18 and 24 months to complete a full cycle.The glycogen generation capacity is entirely dependent on, and determined by, the operating levels of the mitochondria in all of the cells of the human body; however, the relation between the energy generated by the mitochondria and the glycogen capacity is very loose and is mediated by many biochemical pathways. The energy output of full healthy mitochondrial function can be predicted exactly by a complicated theoretical argument, but this argument is not straightforward, as most energy is consumed by the brain and is not easily measurable.

Diagnosis
Mitochondrial diseases are usually detected by analysing muscle samples, where the presence of these organelles is higher. The most common tests for the detection of these diseases are:

Southern blot to detect big deletions or duplications
Polymerase chain reaction and specific mutation testing
Sequencing

Treatments
Although research is ongoing, treatment options are currently limited; vitamins are frequently prescribed, though the evidence for their effectiveness is limited.Pyruvate has been proposed in 2007 as a treatment option. N-acetyl cysteine reverses many models of mitochondrial dysfunction. In the case of mood disorders, specifically bipolar disorder, it is hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options.

Gene therapy prior to conception
Mitochondrial replacement therapy (MRT), where the nuclear DNA is transferred to another healthy egg cell leaving the defective mitochondrial DNA behind, is an IVF treatment procedure. Using a similar pronuclear transfer technique, researchers at Newcastle University led by Douglass Turnbull successfully transplanted healthy DNA in human eggs from women with mitochondrial disease into the eggs of women donors who were unaffected. In such cases, ethical questions have been raised regarding biological motherhood, since the child receives genes and gene regulatory molecules from two different women. Using genetic engineering in attempts to produce babies free of mitochondrial disease is controversial in some circles and raises important ethical issues. A male baby was born in Mexico in 2016 from a mother with Leigh syndrome using MRT.In September 2012 a public consultation was launched in the UK to explore the ethical issues involved. Human genetic engineering was used on a small scale to allow infertile women with genetic defects in their mitochondria to have children.
In June 2013, the United Kingdom government agreed to develop legislation that would legalize the three-person IVF procedure as a treatment to fix or eliminate mitochondrial diseases that are passed on from mother to child </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hair disease and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Grain itch and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Infantile neuroaxonal dystrophy and can you explain it in depth? [/INST] Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills.

Cause
This condition is inherited in an autosomal recessive pattern, which means two copies of the gene (PLA2G6)  in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.

Pathophysiology
Mutations in the PLA2G6 gene have been identified in most individuals with infantile neuroaxonal dystrophy. The PLA2G6 gene provides instructions for making an enzyme called an A2 phospholipase. This enzyme family is involved in metabolizing phospholipids. Phospholipid metabolism is important for many body processes, including helping to keep the cell membrane intact and functioning properly. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane.Mutations in the PLA2G6 gene impair the function of the PLA2 group VI enzyme. This impairment of enzyme function may disrupt cell membrane maintenance and contribute to the development of spheroid bodies in the nerve axons. Although it is unknown how changes in this enzymes function lead to the signs and symptoms of infantile neuroaxonal dystrophy, phospholipid metabolism problems have been seen in both this disorder and a related disorder called pantothenate kinase-associated neurodegeneration. These disorders, as well as the more common Alzheimer disease and Parkinson disease, also are associated with changes in brain iron metabolism. Researchers are studying the links between phospholipid defects, brain iron, and damage to nerve cells, but have not determined how the iron accumulation that occurs in some individuals with infantile neuroaxonal dystrophy may contribute to the features of this disorder.A few individuals with infantile neuroaxonal dystrophy have not been found to have mutations in the PLA2G6 gene. The genetic cause of the condition in these cases is unknown; there is evidence that at least one other gene may be involved.Mutations in the NAGA gene, resulting in alpha-N-acetylgalactosaminidase deficiency, cause an infantile neuroaxonal dystrophy known as Schindler disease.

Diagnosis
In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly.
Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. Generally they have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic) </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Endemic goitre and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Desmosterolosis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Factitious disorder imposed on another and can you explain it in depth? [/INST] Factitious disorder imposed on another (FDIA), also called Munchausen syndrome by proxy (MSbP), is a condition in which a caregiver creates the appearance of health problems in another person, typically their child. This may include injuring the child or altering test samples. The caregiver then presents the person as being sick or injured. Permanent injury or death of the victim may occur as a result of the disorder. The behaviour occurs without a specific benefit to the caregiver.The cause of FDIA is unknown. The primary motive may be to gain attention and manipulate physicians. Risk factors for FDIA include pregnancy related complications and a mother who was abused as a child or has factitious disorder imposed on self. Diagnosis is supported when removing the child from the caregiver results in improvement of symptoms or video surveillance without the knowledge of the caregiver finds concerns. Those affected by the disorder have been subjected to a form of physical abuse and medical neglect.Management of FDIA may require putting the child in foster care. It is not known how effective therapy is for FDIA; it is assumed it may work for those who admit they have a problem. The prevalence of FDIA is unknown, but it appears to be relatively rare. More than 95% of cases involve a persons mother.The prognosis for the caregiver is poor. However, there is a burgeoning literature on possible courses of therapy.The condition was first named, as "Munchausen syndrome by proxy", in 1977 by British pediatrician Roy Meadow. Some aspects of FDIA may represent criminal behavior.

Signs and symptoms
In factitious disorder imposed on another, a caregiver makes a dependent person appear mentally or physically ill in order to gain attention. To perpetuate the medical relationship, the caregiver systematically misrepresents symptoms, fabricates signs, manipulates laboratory tests, or even purposely harms the dependent (e.g. by poisoning, suffocation, infection, physical injury). It is important to note the caregiver is not performing this behavior for obvious external reward, such as money. Studies have shown a mortality rate of between six and ten percent, making it perhaps the most lethal form of abuse.In one study, the average age of the affected individual at the time of diagnosis was four years old. Slightly over 50% were aged 24 months or younger, and 75% were under six years old. The average duration from onset of symptoms to diagnosis was 22 months. By the time of diagnosis, six percent of the affected persons were dead, mostly from apnea (a common result of smothering) or starvation, and seven percent had long-term or permanent injury. About half of the affected had siblings; 25% of the known siblings were dead, and 61% of siblings had symptoms similar to the affected or that were otherwise suspicious. The mother was the perpetrator in 76.5% of the cases, the father in 6.7%.Most present about three medical problems in some combination of the 103 different reported symptoms. The most-frequently reported problems are apnea (26.8% of cases), anorexia or feeding problems (24.6% of cases), diarrhea (20%), seizures (17.5%), cyanosis (blue skin) (11.7%), behavior (10.4%), asthma (9.5%), allergy (9.3%), and fevers (8.6%). Other symptoms include failure to thrive, vomiting, bleeding, rash, and infections. Many of these symptoms are easy to fake because they are subjective. A parent reporting that their child had a fever in the past 24 hours is making a claim that is impossible to prove or disprove. The number and variety of presented symptoms contribute to the difficulty in reaching a proper diagnosis.
Aside from the motive (most commonly attributed to be a gain in attention or sympathy), another feature that differentiates FDIA from "typical" physical child abuse is the degree of premeditation involved. Whereas most physical abuse entails lashing out at a child in response to some behavior (e.g., crying, bedwetting, spilling food), assaults on the FDIA victim tend to be unprovoked and planned.Also unique to this form of abuse is the role that health care providers play by actively, albeit unintentionally, enabling the abuse. By reacting to the concerns and demands of perpetrators, medical professionals are manipulated into a partnership of child maltreatment. Challenging cases that defy simple medical explanations may prompt health care providers to pursue unusual or rare diagnoses, thus allocating even more time to the child and the abuser. Even without prompting, medical professionals may be easily seduced into prescribing diagnostic tests and therapies that may be painful, costly, or potentially injurious to the child. If the health practitioner resists ordering further tests, drugs, procedures, surgeries, or specialists, the FDIA abuser makes the medical system appear negligent for refusing to help a sick child and their selfless parent. Like those with Munchausen syndrome, FDIA perpetrators are known to switch medical providers frequently until they find one that is willing to meet their level of need; this practice is known as "doctor shopping" or "hospital hopping".
The perpetrator continues the abuse because maintaining the child in the role of patient satisfies the abusers needs. The cure for the victim is to separate the child completely from the abuser. When parental visits are allowed, sometimes there is a disastrous outcome for the child. Even when the child is removed, the perpetrator may then abuse another child: a sibling or other child in the family.Factitious disorder imposed on another can have many long-term emotional effects on a child. Depending on their experience of medical interventions, a percentage of children may learn that they are most likely to receive the positive parental attention they crave when they are playing the sick role in front of health care providers. Several case reports describe Munchausen syndrome patients suspected of themselves having been FDIA victims. Seeking personal gratification through illness can thus become a lifelong and multi-generational disorder in some cases.  In stark contrast, other reports suggest survivors of FDIA develop an avoidance of medical treatment with post-traumatic responses to it.The adult caregiver who has abused the child often seems comfortable and not upset over the childs hospitalization. While the child is hospitalized, medical professionals must monitor the caregivers visits to prevent an attempt to worsen the childs condition. In addition, in many jurisdictions, medical professionals have a duty to report such abuse to legal authorities.

Diagnosis
Munchausen syndrome by proxy is a controversial term.  In the World Health Organizations International Statistical Classification of Diseases, 10th Revision (ICD-10), the official diagnosis is factitious disorder (301.51 in ICD-9, F68.12 in ICD-10).  Within the United States, factitious disorder imposed on another (FDIA or FDIoA) was officially recognized as a disorder in 2013, while in the United Kingdom, it is known as fabricated or induced illness by carers (FII).In DSM-5, the diagnostic manual published by the American Psychiatric Association in 2013, this disorder is listed under 300.19 Factitious disorder. This, in turn, encompasses two types:
Factitious Disorder Imposed on Self
Factitious Disorder Imposed on Another (Previously Factitious Disorder by Proxy); the diagnosis is assigned to the perpetrator; the person affected may be assigned an abuse diagnosis (e.g. child abuse).Both types include an optional specifier to identify if the observed behavior was a single episode or part of recurrent episodes.

Warning signs
Warning signs of the disorder include:
A child who has one or more medical problems that do not respond to treatment or that follow an unusual course that is persistent, puzzling, and unexplained.
Physical or laboratory findings that are highly unusual, discrepant with patients presentation or history, or physically or clinically impossible.
A parent who appears medically knowledgeable, fascinated with medical details and hospital gossip, appears to enjoy the hospital environment, and expresses interest in the details of other patients problems.
A highly attentive parent who is reluctant to leave their childs side and who themselves seem to require constant attention.
A parent who appears unusually calm in the face of serious difficulties in their childs medical course while being highly supportive and encouraging of the physician, or one who is angry, devalues staff, and demands further intervention, more procedures, second opinions, and transfers to more sophisticated facilities.
The suspected parent may work in the health-care field themselves or profess an interest in a health-related job.
The signs and symptoms of a childs illness may lessen or simply vanish in the parents absence (hospitalization and careful monitoring may be necessary to establish this causal relationship).
A family history of similar or unexplained illness or death in a sibling.
A parent with symptoms similar to their childs own medical problems or an illness history that itself is puzzling and unusual.
A suspected emotionally distant relationship between parents; the spouse often fails to visit the patient and has little contact with physicians even when the child is hospitalized with a serious illness.
A parent who reports dramatic, negative events, such as house fires, burglaries, or car accidents, that affect them and their family while their child is undergoing treatment.
A parent who seems to have an insatiable need for adulation or who makes self-serving efforts for public acknowledgment of their abilities.
A child who inexplicably deteriorates whenever discharge is planned.
A child that looks for cueing from a parent in order to feign illness when medical personnel are present.
A child that is overly articulate regarding medical terminology and their own disease process for their age.
A child that presents to the Emergency Department with a history of repeat illness, injury, or hospitalization.

Epidemiology
FDIA is rare. Incidence rate estimates range from 1 to 28 per million children, although some assume that it may be much more common.One study showed that in 93 percent of FDIA cases, the abuser is the mother or another female guardian or caregiver.  A psychodynamic model of this kind of maternal abuse exists.Fathers and other male caregivers have been the perpetrators in only seven percent of the cases studied.  When they are not actively involved in the abuse, the fathers or male guardians of FDIA victims are often described as being distant, emotionally disengaged, and powerless. These men play a passive role in FDIA by being frequently absent from the home and rarely visiting the hospitalized child. Usually, they vehemently deny the possibility of abuse, even in the face of overwhelming evidence or their childs pleas for help.Overall, male and female children are equally likely to be the victim of FDIA. In the few cases where the father is the perpetrator, however, the victim is three times more likely to be male.One study in Italy found that 4 out of more than 700 children admitted to the hospital met the criteria (0.53%). In this study, stringent diagnostic criteria were used, which required at least one test outcome or event that could not possibly have occurred without deliberate intervention by the FDIA person.

Society and culture
Terminology
The term "Munchausen syndrome by proxy", in the United States, has never officially been included as a discrete mental disorder by the American Psychiatric Association, which publishes the Diagnostic and Statistical Manual of Mental Disorders (DSM), now in its fifth edition. Although the DSM-III (1980) and DSM-III-R (1987) included Munchausen syndrome, they did not include MSbP.  DSM-IV (1994) and DSM-IV-TR (2000) added MSbP as a proposal only, and although it was finally recognized as a disorder in DSM-5 (2013), each of the last three editions of the DSM designated the disorder by a different name.
FDIA has been given different names in different places and at different times. What follows is a partial list of alternative names that have been either used or proposed (with approximate dates):
Factitious Disorder Imposed on Another (current) (U.S., 2013)  American Psychiatric Association, DSM-5
Factitious Disorder by Proxy (FDP, FDbP) (proposed) (U.S., 2000)  American Psychiatric Association, DSM-IV-TR
Fictitious Disorder by Proxy (FDP, FDbP) (proposed) (U.S., 1994)  American Psychiatric Association, DSM-IV
Fabricated or Induced Illness by Carers (FII) (U.K., 2002)  The Royal College of Pediatrics and Child Health
Factitious Illness by Proxy (1996)  World Health Organization
Pediatric Condition Falsification (PCF) (proposed) (U.S., 2002)  American Professional Society on the Abuse of Children proposed this term to diagnose the victim (child); the perpetrator (caregiver) would be diagnosed "factitious disorder by proxy"; MSbP would be retained as the name applied to the disorder that contains these two elements, a diagnosis in the child and a diagnosis in the caretaker.
Induced Illness (Munchausen Syndrome by Proxy) (Ireland, 1999–2002)  Department of Health and Children
Munchausen Syndrome by Proxy (2002) Professor Roy Meadow.
Meadows Syndrome (1984–1987) named after Roy Meadow.  This label, however, had already been in use since 1957 to describe a completely unrelated and rare form of cardiomyopathy.
Polle Syndrome (1977–1984)  coined by Burman and Stevens, from the then-common belief that Baron Münchhausens second wife gave birth to a daughter named Polle during their marriage. The baron declared that the baby was not his, and the child died from "seizures" at the age of 10 months. The name fell out of favor after 1984, when it was discovered that Polle was not the babys name, but rather was the name of her mothers hometown.While it initially included only the infliction of harmful medical care, the term has subsequently been extended to include cases in which the only harm arose from medical neglect, noncompliance, or even educational interference. The term is derived from Munchausen syndrome, a psychiatric factitious disorder wherein those affected feign disease, illness, or psychological trauma to draw attention, sympathy, or reassurance to themselves. Munchausen syndrome by proxy perpetrators, by contrast, are willing to fulfill their need for positive attention by hurting their own child, thereby assuming the sick role onto their child, by proxy. These proxies then gain personal attention and support by taking on this fictitious "hero role" and receive positive attention from others, by appearing to care for and save their so-called sick child. They are named after Baron Munchausen, a literary character based on Hieronymus Karl Friedrich, Freiherr von Münchhausen (1720–1797), a German nobleman and well-known storyteller. In 1785, writer and con artist Rudolf Erich Raspe anonymously published a book in which a fictional version of "Baron Munchausen" tells fantastic and impossible stories about himself, establishing a popular literary archetype of a bombastic exaggerator.

Initial description
"Munchausen syndrome" was first described by R. Asher in 1951 as when someone invents or exaggerates medical symptoms, sometimes engaging in self-harm, to gain attention or sympathy.
The term "Munchausen syndrome by proxy" was first coined by John Money and June Faith Werlwas in a 1976 paper titled Folie à deux in the parents of psychosocial dwarfs: Two cases to describe the abuse-induced and neglect-induced symptoms of the syndrome of abuse dwarfism. That same year, Sneed and Bell wrote an article titled The Dauphin of Munchausen: factitious passage of renal stones in a child.According to other sources, the term was created by the British pediatrician Roy Meadow in 1977.  In 1977, Meadow – then professor of pediatrics at the University of Leeds, England – described the extraordinary behavior of two mothers. According to Meadow, one had poisoned her toddler with excessive quantities of salt. The other had introduced her own blood into her babys urine sample. This second case occurred during a series of Outpatient visits to the Paediatric Clinic of Dr. Bill Arrowsmith at Doncaster Royal Infirmary. He referred to this behavior as Munchausen syndrome by proxy (MSbP).The medical community was initially skeptical of FDIAs existence, but it gradually gained acceptance as a recognized condition.

Controversy
During the 1990s and early 2000s, Roy Meadow was an expert witness in several murder cases involving MSbP/FII. Meadow was knighted for his work for child protection, though later, his reputation, and consequently the credibility of MSbP, became damaged when several convictions of child killing, in which he acted as an expert witness, were overturned. The mothers in those cases were wrongly convicted of murdering two or more of their children, and had already been imprisoned for up to six years.One case was that of Sally Clark. Clark was a lawyer wrongly convicted in 1999 of the murder of her two baby sons, largely on the basis of Meadows evidence. As an expert witness for the prosecution, Meadow asserted that the odds of there being two unexplained infant deaths in one family were one in 73 million. That figure was crucial in sending Clark to jail but was hotly disputed by the Royal Statistical Society, who wrote to the Lord Chancellor to complain.  It was subsequently shown that the true odds were much greater once other factors (e.g. genetic or environmental) were taken into consideration, meaning that there was a significantly higher likelihood of two deaths happening as a chance occurrence than Meadow had claimed during the trial. Those odds in fact range from a low of 1:8500 to as high as 1:200.  It emerged later that there was clear evidence of a Staphylococcus aureus infection that had spread as far as the childs cerebrospinal fluid.  Clark was released in January 2003 after three judges quashed her convictions in the Court of Appeal in London, but suffering from catastrophic trauma of the experience, she later died from alcohol poisoning.  Meadow was involved as a prosecution witness in three other high-profile cases resulting in mothers being imprisoned and subsequently cleared of wrongdoing: Trupti Patel, Angela Cannings and Donna Anthony.In 2003, Lord Howe, the Opposition spokesman on health, accused Meadow of inventing a "theory without science" and refusing to produce any real evidence to prove that Munchausen syndrome by proxy actually exists. It is important to distinguish between the act of harming a child, which can be easily verified, and motive, which is much harder to verify and which FDIA tries to explain. For example, a caregiver may wish to harm a child out of malice and then attempt to conceal it as illness to avoid detection of abuse, rather than to draw attention and sympathy.
The distinction is often crucial in criminal proceedings, in which the prosecutor must prove both the act and the mental element constituting a crime to establish guilt. In most legal jurisdictions, a doctor can give expert witness testimony as to whether a child was being harmed but cannot speculate regarding the motive of the caregiver. FII merely refers to the fact that illness is induced or fabricated and does not specifically limit the motives of such acts to a caregivers need for attention and/or sympathy.
In all, around 250 cases resulting in conviction in which Meadow was an expert witness were reviewed, with few changes, but all where the only evidence was Meadows expert testimony were overturned. Meadow was investigated by the British General Medical Council (GMC) over evidence he gave in the Sally Clark trial. In July 2005, the GMC declared Meadow guilty of "serious professional misconduct", and he was struck off the medical register for giving "erroneous" and "misleading" evidence.
At appeal, High Court judge Mr. Justice Collins said that the severity of his punishment "approaches the irrational" and set it aside.Collinss judgment raises important points concerning the liability of expert witnesses – his view is that referral to the GMC by the losing side is an unacceptable threat and that only the Court should decide whether its witnesses are seriously deficient and refer them to their professional bodies.In addition to the controversy surrounding expert witnesses, an article appeared in the forensic literature that detailed legal cases involving controversy surrounding the murder suspect. The article provides a brief review of the research and criminal cases involving Munchausen syndrome by proxy in which psychopathic mothers and caregivers were the murderers. It also briefly describes the importance of gathering behavioral data, including observations of the parents who commit the criminal acts. The article references the 1997 work of Southall, Plunkett, Banks, Falkov, and Samuels, in which covert video recorders were used to monitor the hospital rooms of suspected FDIA victims. In 30 out of 39 cases, a parent was observed intentionally suffocating their child; in two they were seen attempting to poison a child; in another, the mother deliberately broke her three-month-old daughters arm. Upon further investigation, those 39 patients, ages 1 month to 3 years old, had 41 siblings; 12 of those had died suddenly and unexpectedly.  The use of covert video, while apparently extremely effective, raises controversy in some jurisdictions over privacy rights.

Legal status
In most legal jurisdictions, doctors are allowed to give evidence only in regard to whether the child is being harmed. They are not allowed to give evidence in regard to the motive. Australia and the UK have established the legal precedent that FDIA does not exist as a medico-legal entity.
In a June 2004 appeal hearing, the Supreme Court of Queensland, Australia, stated:

As the term factitious disorder (Munchausens Syndrome) by proxy is merely descriptive of a behavior, not a psychiatrically identifiable illness or condition, it does not relate to an organized or recognized reliable body of knowledge or experience. Dr. Reddans evidence was inadmissible.
The Queensland Supreme Court further ruled that the determination of whether or not a defendant had caused intentional harm to a child was a matter for the jury to decide and not for the determination by expert witnesses:

The diagnosis of Doctors Pincus, Withers, and OLoughlin that the appellant intentionally caused her children to receive unnecessary treatment through her own acts and the false reporting of symptoms of the factitious disorder (Munchausen Syndrome) by proxy is not a diagnosis of a recognized medical condition, disorder, or syndrome. It is simply placing her within the medical term used in the category of people exhibiting such behavior. In that sense, their opinions were not expert evidence because they related to matters that could be decided on the evidence by ordinary jurors. The essential issue as to whether the appellant reported or fabricated false symptoms or did acts to intentionally cause unnecessary medical procedures to injure her children was a matter for the jurys determination. The evidence of Doctors Pincus, Withers, and OLoughlin that the appellant was exhibiting the behavior of factitious disorder (Munchausen syndrome by proxy) should have been excluded.
Principles of law and implications for legal processes that may be deduced from these findings are that:

Any matters brought before a Court of Law should be determined by the facts, not by suppositions attached to a label describing a behavior, i.e., MSBP/FII/FDBP;
MSBP/FII/FDBP is not a mental disorder (i.e., not defined as such in DSM IV), and the evidence of a psychiatrist should not therefore be admissible;
MSBP/FII/FDBP has been stated to be a behavior describing a form of child abuse and not a medical diagnosis of either a parent or a child. A medical practitioner cannot therefore state that a person "suffers" from MSBP/FII/FDBP, and such evidence should also therefore be inadmissible. The evidence of a medical practitioner should be confined to what they observed and heard and what forensic information was found by recognized medical investigative procedures;
A label used to describe a behavior is not helpful in determining guilt and is prejudicial. By applying an ambiguous label of MSBP/FII to a woman is implying guilt without factual supportive and corroborative evidence;
The assertion that other people may behave in this way, i.e., fabricate and/or induce illness in children to gain attention for themselves (FII/MSBP/FDBY), contained within the label is not factual evidence that this individual has behaved in this way. Again therefore, the application of the label is prejudicial to fairness and a finding based on fact.The Queensland Judgment was adopted into English law in the High Court of Justice by Mr. Justice Ryder. In his final conclusions regarding Factitious Disorder, Ryder states that:

I have considered and respectfully adopt the dicta of the Supreme Court of Queensland in R v. LM [2004] QCA 192 at paragraph 62 and 66. I take full account of the criminal law and foreign jurisdictional contexts of that decision but I am persuaded by the following argument upon its face that it is valid to the English law of evidence as applied to children proceedings.The terms "Munchausen syndrome by proxy" and "factitious (and induced) illness (by proxy)" are child protection labels that are merely descriptions of a range of behaviors, not a pediatric, psychiatric or psychological disease that is identifiable. The terms do not relate to an organized or universally recognized body of knowledge or experience that has identified a medical disease (i.e. an illness or condition) and there are no internationally accepted medical criteria for the use of either label.In reality, the use of the label is intended to connote that in the individual case there are materials susceptible of analysis by pediatricians and of findings of fact by a court concerning fabrication, exaggeration, minimization or omission in the reporting of symptoms and evidence of harm by act, omission or suggestion (induction). Where such facts exist the context and assessments can provide an insight into the degree of risk that a child may face and the court is likely to be assisted as to that aspect by psychiatric and/or psychological expert evidence.All of the above ought to be self evident and has in any event been the established teaching of leading pediatricians, psychiatrists and psychologists for some while. That is not to minimize the nature and extent of professional debate about this issue which remains significant, nor to minimize the extreme nature of the risk that is identified in a small number of cases.In these circumstances, evidence as to the existence of MSBP or FII in any individual case is as likely to be evidence of mere propensity which would be inadmissible at the fact finding stage (see Re CB and JB supra). For my part, I would consign the label MSBP to the history books and however useful FII may apparently be to the child protection practitioner I would caution against its use other than as a factual description of a series of incidents or behaviors that should then be accurately set out (and even then only in the hands of the pediatrician or psychiatrist/psychologist). I cannot emphasis too strongly that my conclusion cannot be used as a reason to re-open the many cases where facts have been found against a carer and the label MSBP or FII has been attached to that carers behavior. What I seek to caution against is the use of the label as a substitute for factual analysis and risk assessment.
In his book Playing Sick (2004), Marc Feldman notes that such findings have been in the minority among U.S. and even Australian courts. Pediatricians and other physicians have banded together to oppose limitations on child-abuse professionals whose work includes FII detection. The April 2007 issue of the journal Pediatrics specifically mentions Meadow as an individual who has been inappropriately maligned.
In the context of child protection (a child being removed from the custody of a parent), the Australian state of New South Wales uses a "on the balance of probabilities" test, rather than a "beyond reasonable doubt" test. Therefore, in the case "The Secretary, Department of Family and Community Services and the Harper Children [2016] NSWChC 3", the expert testimony of Professor David Isaacs that a certain blood test result was "highly unlikely" to occur naturally or accidentally (without any speculation about motive), was sufficient to refuse the return of the affected child and his younger siblings to the mother. The children had initially been removed from the mothers custody after the blood test results became known. The fact that the affected child quickly improved both medically and behaviourly after being removed was also a factor.

Notable cases
Beverley Allitt, a British nurse who murdered four children and injured a further nine in 1991 at Grantham and Kesteven Hospital, Lincolnshire, was diagnosed with Munchausen syndrome by proxy.Wendi Michelle Scott is a Frederick, Maryland, mother who was charged with sickening her four-year-old daughter.The book Sickened, by Julie Gregory, details her life growing up with a mother who had Munchausen by proxy, who took her to various doctors, coached her to act sicker than she was and to exaggerate her symptoms, and who demanded increasingly invasive procedures to diagnose Gregorys enforced imaginary illnesses.Lisa Hayden-Johnson of Devon was jailed for three years and three months after subjecting her son to a total of 325 medical actions – including being forced to use a wheelchair and being fed through a tube in his stomach. She claimed her son had a long list of illnesses including diabetes, food allergies, cerebral palsy, and cystic fibrosis, describing him as "the most ill child in Britain" and receiving numerous cash donations and charity gifts, including two cruises.In the mid-1990s, Kathy Bush gained public sympathy for the plight of her daughter, Jennifer, who by the age of 8 had undergone 40 surgeries and spent over 640 days in hospitals for gastrointestinal disorders. The acclaim led to a visit with first lady Hillary Clinton, who championed the Bushs plight as evidence of need for medical reform. However, in 1996, Kathy Bush was arrested and charged with child abuse and Medicaid fraud, accused of sabotaging Jennifers medical equipment and drugs to agitate and prolong her illness. Jennifer was moved to foster care where she quickly regained her health. The prosecutors claimed Kathy was driven by Munchausen Syndrome by Proxy, and she was convicted to a five-year sentence in 1999. Kathy was released after serving three years in 2005, always maintaining her innocence, and having gotten back in contact with Jennifer via correspondence.In 2014, 26-year-old Lacey Spears was charged in Westchester County, New York, with second-degree depraved murder and first-degree manslaughter.  She fed her son dangerous amounts of salt after she conducted research on the Internet about its effects. Her actions were allegedly motivated by the social media attention she gained on Facebook, Twitter, and blogs. She was convicted of second-degree murder on March 2, 2015, and sentenced to 20 years to life in prison.Dee Dee Blanchard was a Missouri mother who was murdered by her daughter and a boyfriend in 2015 after having claimed for years that her daughter, Gypsy Rose, was sick and disabled; to the point of shaving her head, making her use a wheelchair in public, and subjecting her to unnecessary medication and surgery. Gypsy possessed no outstanding illnesses. Feldman said it is the first case he is aware of in a quarter-century of research where the victim killed the abuser. Their story was shown on HBOs documentary film Mommy Dead and Dearest and is featured in the Hulu limited series The Act </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Tenonitis and can you explain it in depth? [/INST] Tenonitis is a rare eye disease that is represented by inflammation of Tenons capsule. Tenons capsule, also known as the fascial sheath of the eyeball, is a structure surrounding the eyeball, and when it becomes inflamed it may cause issues in regards to vision. Also known as orbital tenonitis, tenonitis is associated with the SLC26A3 gene. The inflammation of the Tenon capsule resulting from heightened blood flow may also affect the lacrimal gland and the extraocular muscles.

Signs and Symptoms
Signs and symptoms depend on the severity of the case with tenonitis. In mild cases it may just be an uncomfortable sensation in the eye socket. In extreme cases it may cause permanent blindness or eye removal is needed.

Swelling
Intraocular pressure
Blindness

Causes
There are no specific causes of this disease. With this being so rare not enough research has been allocated to pinpoint a specific cause of this disease. The main thing that we know about this disease is that the inflammation of the Tenon capsule may be related to macular retinal edema and intraocular pressure quantitative trait locus.

Mechanism
With the lack of research and understanding about this specific disease it is hard to come up with a mechanism that outlines how this arises in the body. Although we cannot pinpoint specifically how it occurs, there are some findings that may help us get to that point in the future. A gene that is associated with orbital tenonitis is the SLC26A3 gene. This gene mediates chloride and bicarbonate exchange and additionally transports sulfate and other anions at the apical membrane, part of the plasma membrane of enterocytes. It is also known that related phenotypes are  Increased shRNA abundance (Z-score > 2).

Diagnosis
Tenonitis can be identified and diagnosed a few different ways. Tenons capsule may have inflammation from a disease called idiopathic orbital inflammation syndrome </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Multiple evanescent white dot syndrome and can you explain it in depth? [/INST] Multiple evanescent white dot syndrome (MEWDS) is an uncommon inflammatory condition of the retina that typically affects otherwise healthy young females in the second to fourth decades of life.
The typical patient with MEWDS is a healthy middle aged female age 15-50 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Chordee and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Seminal vesicles and can you explain it in depth? [/INST] The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder of some male mammals. They secrete fluid that partly composes the semen.
The vesicles are 5–10 cm in size, 3–5 cm in diameter, and are located between the bladder and the rectum. They have multiple outpouchings which contain secretory glands, which join together with the vas deferens at the ejaculatory duct. They receive blood from the vesiculodeferential artery, and drain into the vesiculodeferential veins. The glands are lined with column-shaped and cuboidal cells. The vesicles are present in many groups of mammals, but not marsupials, monotremes or carnivores.
Inflammation of the seminal vesicles is called seminal vesiculitis, most often is due to bacterial infection as a result of a sexually transmitted disease or following a surgical procedure. Seminal vesiculitis can cause pain in the lower abdomen, scrotum, penis or peritoneum, painful ejaculation, and blood in the semen. It is usually treated with antibiotics, although may require surgical drainage in complicated cases. Other conditions may affect the vesicles, including congenital abnormalities such as failure or incomplete formation, and, uncommonly, tumours.
The seminal vesicles have been described as early as the second century AD by Galen, although the vesicles only received their name much later, as they were initially described using the term from which the word prostate is derived.

Structure
The seminal vesicles are a pair of glands in males that are positioned below the urinary bladder and at the end of the vasa deferentia, where they enter the prostate. Each vesicle is a coiled and folded tube, with occasional outpouchings termed diverticula in its wall. The lower part of the tube ends as a straight tube called the excretory duct which joins with the vas deferens of that side of the body to form an ejaculatory duct. The ejaculatory ducts pass through the prostate gland before opening separately into the verumontanum of the prostatic urethra. The vesicles are between 5–10 cm in size, 3–5 cm in diameter, and have a volume of around 13 mL.The vesicles receive blood supply from the vesiculodeferential artery, and also from the inferior vesical artery. The vesiculodeferential artery arises from the umbilical arteries, which branch directly from the internal iliac arteries. Blood is drained into the vesiculodeferential veins and the inferior vesical plexus, which drain into the internal iliac veins. Lymphatic drainage occurs along the venous routes, draining into the internal iliac nodes.The vesicles lie behind the bladder at the end of the vasa deferentia. They lie in the space between the bladder and the rectum; the bladder and prostate lie in front, the tip of the ureter as it enters the bladder above, and Denonvilliers fascia and the rectum behind.

Development
In the developing embryo, at the hind end lies a cloaca. This, over the fourth to the seventh week, divides into a urogenital sinus and the beginnings of the anal canal, with a wall forming between these two inpouchings called the urorectal septum. Two ducts form next to each other that connect to the urogenital sinus; the mesonephric duct and the paramesonephric duct, which go on to form the reproductive tracts of the male and female respectively.In the male, under the influence of testosterone, the mesonephric duct proliferates, forming the epididymis, ductus deferens and, via a small outpouching near the developing prostate, the seminal vesicles. Sertoli cells secrete anti-mullerian hormone, which causes the paramesonephric duct to regress.The development and maintenance of the seminal vesicles, as well as their secretion and size/weight, are highly dependent on androgens. The seminal vesicles contain 5α-reductase, which metabolizes testosterone into its much more potent metabolite, dihydrotestosterone (DHT). The seminal vesicles have also been found to contain luteinizing hormone receptors, and hence may also be regulated by the ligand of this receptor, luteinizing hormone.

Microanatomy
The inner lining of the seminal vesicles (the epithelium) is made of a lining of interspersed column-shaped and cube-shaped cells. There are varying descriptions of the lining as being pseudostratified and consisting of column-shaped cells only. When viewed under a microscope, the cells are seen to have large bubbles in their interior. This is because their interior, called cytoplasm, contains lipid droplets involved in secretion during ejaculation. The tissue of the seminal vesicles is full of glands, spaced irregularly. As well as glands, the seminal vesicles contain smooth muscle and connective tissue. This fibrous and muscular tissue surrounds the glands, helping to expel their contents. The outer surface of the glands is covered in peritoneum.

Function
The seminal vesicles secrete a significant proportion of the fluid that ultimately becomes semen. Fluid is secreted from the ejaculatory ducts of the vesicles into the vas deferens, where it becomes part of semen. This then passes through the urethra, where it is ejaculated during a male sexual response.About 70-85% of the seminal fluid in humans originates from the seminal vesicles. The fluid consists of nutrients including fructose and citric acid, prostaglandins, and fibrinogen. Nutrients help support sperm until fertilisation occurs; prostaglandins may also assist by softening mucous of the cervix, and by causing reverse contractions of parts of the female reproductive tract such as the fallopian tubes, to ensure that sperm are less likely to be expelled.

Clinical significance
Disease
Diseases of the Seminal vesicles as opposed to that of prostate gland are extremely rare and are infrequently reported in the medical literature.Congenital anomalies associated with the seminal vesicles include failure to develop, either completely (agenesis) or partially (hypoplasia), and cysts. Failure of the vesicles to form is often associated with absent vas deferens, or an abnormal connection between the vas deferens and the ureter. The seminal vesicles may also be affected by cysts, amyloidosis, and stones. Stones or cysts that become infected, or obstruct the vas deferens or seminal vesicles, may require surgical intervention.Seminal vesiculitis (also known as spermatocystitis) is an inflammation of the seminal vesicles, most often caused by bacterial infection. Symptoms can include vague back or lower abdominal pain; pain of the penis, scrotum or peritoneum; painful ejaculation; blood in the semen on ejaculation; irritative and obstructive voiding symptoms; and impotence. Infection may be due to sexually transmitted infections, as a complication of a procedure such as prostate biopsy. It is usually treated with antibiotics. If a person experiences ongoing discomfort, transurethral seminal vesiculoscopy may be considered. Intervention in the form of drainage through the skin or surgery may also be required if the infection becomes an abscess. The seminal vesicles may also be affected by tuberculosis, schistosomiasis and hydatid disease. These diseases are investigated, diagnosed and treated according to the underlying disease.Benign tumours of the seminal vesicles are rare. When they do occur, they are usually papillary adenomas and cystadenomas. They do not cause elevation of tumour markers, and are usually diagnosed based examination of tissue that has been removed after surgery. Primary adenocarcinoma of the seminal vesicles, although rare, constitutes the most common malignant cancer of the seminal vesicles; that said, the majority of malignant cancers affecting the vesicles are lesions that have extended into the vesicles from nearby parts of the body. When adenocarcinoma occurs, it can cause blood in the urine, blood in the semen, painful urination, urinary retention, or even urinary obstruction. Adenocarcinomata are usually diagnosed after they are excised, based on tissue diagnosis. Some produce the tumour marker Ca-125, which can be used to monitor for reoccurence afterwards. Even rarer neoplasms include sarcoma, squamous cell carcinoma, yolk sac tumor, neuroendocrine carcinoma, paraganglioma, epithelial stromal tumors and lymphoma.

Investigations
Symptoms due to diseases of the seminal vesicles may be vague and not able to be specifically attributable to the vesicles themselves; additionally, some conditions such as tumours or cysts may not cause any symptoms at all. When diseases is suspected, such as due to pain on ejaculation, blood in the urine, infertility, due to urinary tract obstruction, further investigations may be conducted.A digital rectal examination, which involves a finger inserted by a medical practitioner through the anus, may cause greater than usual tenderness of the prostate gland, or may reveal a large seminal vesicle </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Biotinidase deficiency and can you explain it in depth? [/INST] Biotinidase deficiency is an autosomal recessive metabolic disorder in which biotin is not released from proteins in the diet during digestion or from normal protein turnover in the cell. This situation results in biotin deficiency.
Biotin is an important water-soluble nutrient that aids in the metabolism of fats, carbohydrates, and proteins.  Biotin deficiency can result in behavioral disorders, lack of coordination, learning disabilities and seizures. Biotin supplementation can alleviate and sometimes totally stop such symptoms.

Signs and symptoms
Signs and symptoms of a biotinidase deficiency can appear several days after birth. These include seizures, hypotonia and muscle/limb weakness, ataxia, paresis, hearing loss, optic atrophy, skin rashes (including seborrheic dermatitis and psoriasis), and alopecia. If left untreated, the disorder can rapidly lead to coma and death.Biotinidase deficiency can also appear later in life. This is referred to as "late-onset" biotinidase deficiency. The symptoms are similar, but perhaps more mild, because if an individual survives the neonatal period they likely have some residual activity of biotin-related enzymes. Studies have noted individuals who were asymptomatic until adolescence or early adulthood. One study pointed out that untreated individuals may not show symptoms until age 21. Furthermore, in rare cases, even individuals with profound deficiencies of biotinidase can be asymptomatic.Symptom severity is predictably correlated with the severity of the enzyme defect. Profound biotinidase deficiency refers to situations where enzyme activity is 10% or less. Individuals with partial biotinidase deficiency may have enzyme activity of 10-30%.Functionally, there is no significant difference between dietary biotin deficiency and genetic loss of biotin-related enzyme activity. In both cases, supplementation with biotin can often restore normal metabolic function and proper catabolism of leucine and isoleucine.The symptoms of biotinidase deficiency (and dietary deficiency of biotin) can be quite severe. A 2004 case study from Metametrix detailed the effects of biotin deficiency, including aggression, cognitive delay, and reduced immune function.

Genetics
Mutations in the BTD gene cause biotinidase deficiency. Biotinidase is the enzyme that is made by the BTD gene. Many mutations that cause the enzyme to be nonfunctional or to be produced at extremely low levels have been identified. Biotin is a vitamin that is chemically bound to proteins. (Most vitamins are only loosely associated with proteins.) Without biotinidase activity, the vitamin biotin cannot be separated from foods and therefore cannot be used by the body. Another function of the biotinidase enzyme is to recycle biotin from enzymes that are important in metabolism (processing of substances in cells). When biotin is lacking, specific enzymes called carboxylases cannot process certain proteins, fats, or carbohydrates. Specifically, two essential branched-chain amino acids (leucine and isoleucine) are metabolized differently.Individuals lacking functional biotinidase enzymes can still have normal carboxylase activity if they ingest adequate amounts of biotin. The standard treatment regimen calls for 5–10 mg of biotin per day.Biotinidase deficiency is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the defective gene - one from each parent - must be inherited for a person to be affected by the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder, but are carriers of one copy of the defective gene.  If both parents are carriers for the biotinidase deficiency, there is a 25% chance that their child will be born with it, a 50% chance the child will be a carrier, and a 25% chance the child will be unaffected.The chromosomal locus is at 3p25. The BTD gene has 4 exons of lengths 79 bp, 265 bp, 150 bp and 1502 bp, respectively.  There are at least 21 different mutations that have been found to lead to biotinidase deficiency. The most common mutations in severe biotinidase deficiency (<10% normal enzyme activity) are: p. Cys33PhefsX36, p.Gln456His, p.Arg538Cys, p.Asp444His, and p.[Ala171Thr;Asp444His]. Almost all individuals with partial biotinidase deficiency (10-30% enzyme activity) have the mutation p.Asp444His in one allele of the BTD gene in combination with a second allele.

Pathophysiology
Symptoms of the deficiency are caused by the inability to reuse biotin molecules that are needed for cell growth, production of fatty acids and the metabolism of fats and amino acids. If left untreated, the symptoms can lead to later problems such as comas or death. Unless treatment is administered on a regular basis, symptoms can return at any point during the lifespan.

Diagnosis
Biotinidase deficiency can be found by genetic testing.  This is often done at birth as part of newborn screening in several states throughout the United States.  Results are found through testing a small amount of blood gathered through a heel prick of the infant.  As not all states require that this test be done, it is often skipped in those where such testing is not required.  Biotinidase deficiency can also be found by sequencing the BTD gene, particularly in those with a family history or known familial gene mutation.

Treatment
Treatment is possible but unless continued daily, problems may arise. Currently, this is done through supplementation of 5–10 mg of oral biotin a day. If symptoms have begun to show, standard treatments can take care of them, such as hearing aids for poor hearing.

Epidemiology
Based on the results of worldwide screening of biotinidase deficiency in 1991, the incidence of the disorder is:
5 in 137,401 for profound biotinidase deficiency

One in 109,921 for partial biotinidase deficiency
One in 61,067 for the combined incidence of profound and partial biotinidase deficiency
Carrier frequency in the general population is approximately one in 120.

See also
Biotin
Biotin deficiency
Multiple carboxylase deficiency
Holocarboxylase synthetase deficiency
3-Methylcrotonyl-CoA carboxylase deficiency

References
Further reading
Dobrowolski, Steven F.; Angeletti, Janine; Banas, Richard A.; Naylor, Edwin W. (2003). "Real time PCR assays to detect common mutations in the biotinidase gene and application of mutational analysis to newborn screening for biotinidase deficiency". Molecular Genetics and Metabolism. 78 (2): 100–7. doi:10.1016/S1096-7192(02)00231-7. PMID 12618081.
McMahon, Robert J. (2002). "Biotin in metabolism and molecular biology". Annual Review of Nutrition. 22: 221–39. doi:10.1146/annurev.nutr.22.121101.112819. PMID 12055344.
C. Neto, E.; Schulte, J.; Rubim, R.; Lewis, E.; Demari, J.; Castilhos, C.; Brites, A.; Giugliani, R.;  et al. (2004). "Newborn screening for biotinidase deficiency in Brazil: biochemical and molecular characterizations". Brazilian Journal of Medical and Biological Research. 37 (3): 295–9. doi:10.1590/S0100-879X2004000300001. PMID 15060693.
Weber, Peter; Scholl, Sabine; Baumgartner, E Regula (2007). "Outcome in patients with profound biotinidase deficiency: relevance of newborn screening". Developmental Medicine & Child Neurology </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pulmonary consolidation and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Autoimmune encephalitis and can you explain it in depth? [/INST]  </s>