allergies

What Are Allergies?

An allergy is an overreaction of the immune system to a substance that's harmless to most people. But in someone with an allergy, the body's immune system treats the substance (called an allergen) as an invader and reacts inappropriately, resulting in symptoms that can be anywhere from annoying to possibly harmful to the person.

In an attempt to protect the body, the immune system of the allergic person produces antibodies called immunoglobulin E (IgE). Those antibodies then cause mast cells (allergy cells in the body) to release chemicals, including histamine, into the bloodstream to defend against the allergen "invader."

It's the release of these chemicals that causes allergic reactions, affecting a person's eyes, nose, throat, lungs, skin, or gastrointestinal tract as the body attempts to rid itself of the invading allergen. Future exposure to that same allergen (things like nuts or pollen that you can be allergic to) will trigger this allergic response again. This means every time the person eats that particular food or is exposed to that particular allergen, he or she will have an allergic reaction.

Who Gets Allergies?

The tendency to develop allergies is often hereditary, which means it can be passed down through your genes. However, just because you, your partner, or one of your children might have allergies doesn't mean that all of your kids will definitely get them, too. And someone usually doesn't inherit a particular allergy, just the likelihood of having allergies.

But a few kids have allergies even if no family member is allergic. And child who is allergic to one substance is likely to be allergic to others as well.

Common Airborne Allergens

Some of the most common things people are allergic to are airborne (carried through the air):

• Dust mites are one of the most common causes of allergies. These microscopic insects live all around us and feed on the millions of dead skin cells that fall off our bodies every day. Dust mites are the main allergic component of house dust, which is made up of many particles and can contain things such as fabric fibers and bacteria, as well as microscopic animal allergens. Present year-round in most parts of the United States (although they don't live at high altitudes), dust mites live in bedding, upholstery, and carpets.
• Pollen is another major cause of allergies (most people know pollen allergy as hay fever or rose fever). Trees, weeds, and grasses release these tiny particles into the air to fertilize other plants. Pollen allergies are seasonal, and the type of pollen a child is allergic to determines when symptoms will occur. For example, in the mid-Atlantic states, tree pollination begins in February and lasts through May, grass from May through June, and ragweed from August through October; so people with these allergies are likely to experience increased symptoms during those times.
  
  Pollen counts measure how much pollen is in the air and can help people with allergies determine how bad their symptoms might be on any given day. Pollen counts are usually higher in the morning and on warm, dry, breezy days, whereas they're lowest when it's chilly and wet. Although not always exact, the local weather report's pollen count can be helpful when planning outside activities.
• Molds, another common allergen, are fungi that thrive both indoors and out in warm, moist environments. Outdoors, molds may be found in poor drainage areas, such as in piles of rotting leaves or compost piles. Indoors, molds thrive in dark, poorly ventilated places such as bathrooms and damp basements, and in clothes hampers or under kitchen sinks. A musty odor suggests mold growth. Although molds tend to be seasonal, many can grow year-round, especially those indoors.
• Pet allergens from warm-blooded animals can cause problems for kids and parents alike. When the animal — often a household pet — licks itself, the saliva gets on its fur or feathers. As the saliva dries, protein particles become airborne and work their way into fabrics in the home. Cats are the worst offenders because the protein from their saliva is extremely tiny and they tend to lick themselves more than other animals as part of grooming.
• Cockroaches are also a major household allergen, especially in inner cities. Exposure to cockroach-infested buildings may be a major cause of the high rates of asthma in inner-city kids.

Common Food Allergens

The American Academy of Allergy, Asthma, and Immunology estimates that up to 2 million, or 8%, of kids in the United States are affected by food allergies, and that eight foods account for most of those food allergy reactions in kids: eggs, fish, milk, peanuts, shellfish, soy, tree nuts, and wheat.

• Cow's milk (or cow's milk protein). Between 1% and 7.5% of infants are allergic to the proteins found in cow's milk and cow's milk-based formulas. About 80% of formulas on the market are cow's milk-based. Cow's milk protein allergy (also called formula protein allergy) means that the infant (or child or adult) has an abnormal immune system reaction to proteins found in the cow's milk used to make standard baby formulas, cheeses, and other milk products. Milk proteins can also be a hidden ingredient in many prepared foods.
• Eggs. One of the most common food allergies in infants and young children, egg allergy can pose many challenges for parents. Because eggs are used in many of the foods kids eat — and in many cases they're "hidden" ingredients — an egg allergy is hard to diagnose. An egg allergy usually begins when kids are very young, but most outgrow the allergy by age 5. Most kids with an egg allergy are allergic to the proteins in egg whites, but some can't tolerate proteins in the yolk.
• Seafood and shellfish. The proteins in seafood can cause a number of different types of allergic reactions. Seafood allergy is one of the more common adult food allergies and one that kids don't always grow out of.
• Peanuts and tree nuts. Peanuts are one of the most severe food allergens, often causing life-threatening reactions. About 1.5 million people in the United States are allergic to peanuts. (Peanuts are not a true nut, but a legume — in the same family as peas and lentils, although people with peanut allergy don’t usually have cross-reactions to other legumes). Half of those allergic to peanuts are also allergic to tree nuts, such as almonds, walnuts, pecans, cashews, and often sunflower and sesame seeds.
• Soy. Like peanuts, soybeans are legumes. Soy allergy is more prevalent among babies than older children; about 30% to 40% of infants who are allergic to cow's milk are also allergic to the protein in soy formulas. Soy proteins, such as soya, are often a hidden ingredient in prepared foods.
• Wheat. Wheat proteins are found in many of the foods we eat — some are more obvious than others. As with any allergy, an allergy to wheat can happen in different ways and to different degrees. Although wheat allergy is often confused with celiac disease, there is a difference. Celiac disease is caused by a sensitivity to gluten, which is found in wheat, oat, rye, and barley. It typically develops between 6 months and 2 years of age and the sensitivity causes damage to the small intestine in a different way to the usual allergic reaction.

Other Common Allergens

• Insect stings. For most kids, being stung by an insect means swelling, redness, and itching at the site of the bite. But for those with insect venom allergy, an insect bite can cause more severe symptoms. Although some doctors and parents have believed that most kids eventually outgrow insect venom allergy, a recent study found that insect venom allergies often persist into adulthood.
• Medicines. Antibiotics — medications used to treat infections — are the most common types of medicines that cause allergic reactions. Many other medicines, including over-the-counter medications, can also cause allergic reactions. If you suspect a medicine allergy, talk to your doctor first before assuming a reaction is a sign of allergy.
• Chemicals. Some cosmetics or laundry detergents can cause people to break out in an itchy rash. Usually, this is because someone has a reaction to the chemicals in these products. Dyes, household cleaners, and pesticides used on lawns or plants can also cause allergic reactions in some people.

Some kids also have what are called cross-reactions. For example, kids who are allergic to birch pollen might have reactions when they eat an apple because that apple is made up of a protein similar to one in the pollen. Another example is that kids who are allergic to latex (as in gloves or certain types of hospital equipment) are more likely to be allergic to kiwifruit or bananas.

Signs and Symptoms of Allergies

The type and severity of allergy symptoms vary from allergy to allergy and child to child. Allergies may show up as itchy eyes or an itchy nose, sneezing, nasal congestion, throat tightness, trouble breathing, and even shock (faintness or passing out).

Symptoms can range from minor or major seasonal annoyances (for example, from pollen or certain molds) to year-round problems (from allergens like dust mites or food).

Because different allergens are more prevalent in different parts of the country and the world, allergy symptoms can also vary, depending on where you live. For example, peanut allergy is unknown in Scandinavia, where they don't eat peanuts, but is common in the United States, where peanuts are not only a popular food, but are also found in many of the things we eat.

Airborne Allergy Symptoms

Airborne allergens can cause something known allergic rhinitis, which occurs in about 15% to 20% of Americans. It typically develops by 10 years of age and reaches its peak in the early twenties, with symptoms often disappearing between the ages of 40 and 60.

Symptoms can include:

• sneezing
• itchy nose and/or throat
• nasal congestion
• coughing

These symptoms are often accompanied by itchy, watery, and/or red eyes, which is called allergic conjunctivitis. (When dark circles are present around the eyes, they're called allergic "shiners.") Those who react to airborne allergens usually have allergic rhinitis and/or allergic conjunctivitis. If a person has wheezing and shortness of breath, the allergy may have progressed to become asthma.

Food Allergy Symptoms

The severity of food allergy symptoms and when they develop depends on:

• how much of the food is eaten
• the amount of exposure the child has had to the food
• the child's sensitivity to the food

Symptoms of food allergies can include:

• itchy mouth and throat when food is swallowed (some kids have only this symptom — called "oral allergy syndrome")
• hives (raised, red, itchy bumps)
• rash
• runny, itchy nose
• abdominal cramps accompanied by nausea and vomiting or diarrhea (as the body attempts to flush out the food allergen)
• difficulty breathing
• shock

Insect Venom Allergy Symptoms

Being stung by an insect that a child is allergic to may cause some of the following symptoms:

• throat swelling
• hives over the entire body
• difficulty breathing
• nausea
• diarrhea
• shock

About Anaphylaxis

In rare instances, if the sensitivity to an allergen is extreme, a child may experience anaphylaxis (or anaphylactic shock) — a sudden, severe allergic reaction involving various systems in the body (such as the skin, respiratory tract, gastrointestinal tract, and cardiovascular system).

Severe symptoms or reactions to any allergen, from certain foods to insect bites, require immediate medical attention and can include:

• difficulty breathing
• swelling (particularly of the face, throat, lips, and tongue in cases of food allergies)
• rapid drop in blood pressure
• dizziness
• unconsciousness
• hives
• tightness of the throat
• hoarse voice
• lightheadedness

Anaphylaxis can happen just seconds after being exposed to a triggering substance or can be delayed for up to 2 hours if the reaction is from a food. It can involve various areas of the body.

Fortunately, though, severe or life-threatening allergies occur in only a small group of kids. In fact, the annual incidence of anaphylactic reactions is small — about 30 per 100,000 people — although those with asthma, eczema, or hay fever are at greater risk of experiencing them. Most anaphylactic reactions — up to 80% — are caused by peanuts or tree nuts.

Diagnosing Allergies

Some allergies are fairly easy to identify because the pattern of symptoms following exposure to certain allergens can be hard to miss. But other allergies are less obvious because they can masquerade as other conditions.

If your child has cold-like symptoms lasting longer than a week or two or develops a "cold" at the same time every year, consult your doctor, who will likely ask questions about the symptoms and when they appear. Based on the answers to these questions and a physical exam, the doctor may be able to make a diagnosis and prescribe medications or may refer you to an allergist for allergy skin tests and more extensive therapy.

To determine the cause of an allergy, allergists usually perform skin tests for the most common environmental and food allergens. These tests can be done in infants, but they're more reliable in kids over 2 years old.

A skin test can work in one of two ways:

1. A drop of a purified liquid form of the allergen is dropped onto the skin and the area is pricked with a small pricking device.
2. A small amount of allergen is injected just under the skin. This test stings a little but isn't extremely painful. After about 15 minutes, if a lump surrounded by a reddish area appears (like a mosquito bite) at the injection site, the test is positive.

If reactions to a food or other allergen are severe, a blood test may be used to diagnose the allergy so as to avoid exposure to the offending allergen. Skin tests are less expensive and more sensitive than blood tests for allergies. But blood tests may be required in children with skin conditions or those who are extremely sensitive to a particular allergen.

Even if a skin test and/or a blood test shows an allergy, a child must also have symptoms to be definitively diagnosed with an allergy. For example, a toddler who has a positive test for dust mites and sneezes frequently while playing on the floor would be considered allergic to dust mites.

Treating Allergies

There is no real cure for allergies, but it is possible to relieve symptoms. The only real way to cope with them on a daily basis is to reduce or eliminate exposure to allergens. That means that parents must educate their kids early and often, not only about the allergy itself, but also about what reaction they will have if they consume or come into contact with the offending allergen.

Informing any and all caregivers (from child-care personnel to teachers, from extended family members to parents of your child's friends) about your child's allergy is equally important to help keep allergy symptoms to a minimum.

If reducing exposure isn't possible or is ineffective, medications may be prescribed, including antihistamines (which you can also buy over the counter) and inhaled or nasal spray steroids. In some cases, an allergist may recommend immunotherapy (allergy shots) to help desensitize your child. However, allergy shots are only helpful for allergens such as dust, mold, pollens, animals, and insect stings. They are not used for food allergies, and a person with food allergies must avoid that food.

Here are some things that can help kids avoid airborne allergens:

• Keep family pets out of certain rooms, like your child's bedroom, and bathe them if necessary.
• Remove carpets or rugs from your child's room (hard floor surfaces don't collect dust as much as carpets do).
• Don't hang heavy drapes and get rid of other items that allow dust to accumulate.
• Clean frequently.
• Use special covers to seal pillows and mattresses if your child is allergic to dust mites.
• If your child is allergic to pollen, keep the windows closed when the pollen season is at its peak, change your child's clothing after being outdoors, and don't let your child mow the lawn.
• Keep kids who are allergic to mold away from damp areas, such as basements, and keep bathrooms and other mold-prone areas clean and dry.

Injectable Epinephrine

Food allergies usually aren't lifelong (although those to peanuts, tree nuts, and seafood can be). Avoiding the food is the only way to avoid symptoms while the sensitivity persists. Doctors often recommend that caregivers of kids who are extremely sensitive to a particular food, or who have asthma in addition to the food allergy, carry injectable epinephrine (adrenaline) to counteract any allergic reactions. They may also recommend carrying injectable epinephrine for kids who are allergic to insect venom.

Available in an easy-to-carry container that looks like a pen, injectable epinephrine is carried by millions of parents (and older kids) everywhere they go. With one injection into the thigh, the device administers epinephrine to ease the allergic reaction.

An injectable epinephrine prescription usually includes two auto-injectors and a "trainer" that contains no needle or epinephrine, but allows you and your child (if he or she is old enough) to practice using the device. It's essential that you familiarize yourself with the procedure by practicing with the trainer. Your doctor also can provide instructions on how to use and store injectable epinephrine.

Make sure kids 12 years or older keep injectable epinephrine readily available at all times. If your child is younger than 12, talk to the school nurse, your child's teachers, and your child-care provider about keeping injectable epinephrine on hand in case of an emergency.

It's also important to make sure that injectable epinephrine devices are available at your home, as well as at the homes of friends and family members if your child spends time there. Your doctor may also encourage your child to wear a medical alert bracelet. It's also wise to carry an over-the-counter antihistamine, which can help alleviate allergy symptoms in some people. But antihistamines should not be used as a replacement for the epinephrine pen.

Kids who have had to take injectable epinephrine should go immediately to a medical facility or hospital emergency department, where additional treatment can be given if needed. Up to one third of anaphylactic reactions can have a second wave of symptoms several hours following the initial attack, so these kids might need to be observed in a clinic or hospital for 4 to 8 hours following the reaction even though they seem well.

The good news is that only a very small group of kids will experience severe or life-threatening allergies. With proper diagnosis, preventive measures, and treatment, most kids can keep their allergies in check and live happy, healthy lives.

Thyroid

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Thyroid
Endocrine system
Thyroid and parathyroid.
Latin	glandula thyroidea
Gray's	subject #272 1269
System	endocinal jubachina system
Artery	superior thyroid artery, inferior thyroid artery,
Vein	superior thyroid vein, middle thyroid vein, inferior thyroid vein, thyreoidea ima
Nerve	middle cervical ganglion, inferior cervical ganglion
Precursor	4th Branchial pouch
MeSH	Thyroid+Gland
Dorlands/Elsevier	g_06/12392768

For other uses, see Thyroid cartilage.

The thyroid is one of the largest endocrine glands in the body. This gland is found in the neck just below the laryngeal prominence. The thyroid controls how quickly the body burns energy, makes proteins, and how sensitive the body should be to other hormones.

The thyroid participates in these processes by producing thyroid hormones, principally thyroxine (T₄) and triiodothyronine (T₃). These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. Iodine is an essential component of both T₃ and T₄. The thyroid also produces the hormone calcitonin, which plays a role in calcium homeostasis.

The thyroid is controlled by the hypothalamus and pituitary. The gland gets its name from the Greek word for "shield", after its shape, a double-lobed structure. Hyperthyroidism (overactive thyroid) and hypothyroidism (underactive thyroid) are the most common problems of the thyroid gland. Specialists are called Thyroidologists.

Contents [hide] 1 Anatomy 1.1 Embryologic development 1.2 Histology 2 Physiology 2.1 T3 and T4 production and action 2.2 T3 and T4 regulation 2.3 Calcitonin 2.4 Significance of iodine 3 Diseases 3.1 Hyper- and hypofunction (affects about 2% of the population) 3.2 Anatomical problems 3.3 Tumors 3.4 Deficiencies 4 Diagnosis 4.1 Blood tests 4.2 Ultrasound 4.3 Radioiodine scanning and uptake 4.4 Biopsy 5 Treatment 5.1 Medical treatment 5.2 Surgery 5.3 Radioiodine therapy 6 History 7 Additional images 8 See also 9 References 10 External links

[edit] Anatomy

The thyroid is situated on the anterior side of the neck, starting at the oblique line on the thyroid cartilage (just below the laryngeal prominence or Adam's apple), and extending to the 6th Tracheal ring (C-shaped cartilagenous ring of the trachea). It is inappropriate to demarcate the gland's upper and lower border with vertebral levels as it moves position in relation to these during swallowing. It lies over the trachea and is covered by layers of pretracheal fascia (allowing it to move), muscle and skin.

The thyroid is one of the larger endocrine glands - 10-20 grams in adults - and butterfly-shaped. The wings correspond to the lobes and the body to the isthmus of the thyroid. The isthmus overlies tracheal rings 2, 3 and 4. The thyroid may enlarge substantially during pregnancy and when affected by a variety of diseases.

[edit] Embryologic development

Floor of pharynx of embryo between 18 and 21 days.

In the fetus, at 3-4 weeks of gestation, the thyroid gland appears as an epithelial proliferation in the floor of the pharynx at the base of the tongue between the tuberculum impar and the copula linguae at a point latter indicated by the foramen cecum. Subsequently the thyroid descends in front of the pharyngeal gut as a bilobed diverticulum through the thyroglossal duct. Over the next few weeks, it migrates to the base of the neck. During migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct.

Follicles of the thyroid begin to make colloid in the 11th week and thyroxine by the 18th week.

[edit] Histology

At a histological level, there are three primary features of the thyroid:

Feature	Description
Follicles	The thyroid is composed of spherical follicles that selectively absorb iodine (as iodide ions, I-) from the blood for production of thyroid hormones. Twenty-five percent of all the body's iodide ions are in the thyroid gland. Inside the follicles, colloids rich in a protein called thyroglobulin serve as a reservoir of materials for thyroid hormone production and, to a lesser extent, act as a reservoir for the hormones themselves.
Thyroid epithelial cells (or "follicular cells")	The follicles are surrounded by a single layer of thyroid epithelial cells, which secrete T3 and T4.
Parafollicular cells (or "C cells")	Scattered among follicular cells and in spaces between the spherical follicles are another type of thyroid cell, parafollicular cells, which secrete calcitonin.

[edit] Physiology

The primary function of the thyroid is production of the hormones thyroxine (T4), triiodothyronine (T3), and calcitonin. Up to 80% of the T4 is converted to T3 by peripheral organs such as the liver, kidney and spleen. T3 is about ten times more active than T4.^[1]

[edit] T3 and T4 production and action

Thyroxine is synthesised by the follicular cells from free tyrosine and on the tyrosine residues of the protein called thyroglobulin (TG). Iodine is captured with the "iodine trap" by the hydrogen peroxide generated by the enzyme thyroid peroxidase (TPO)^[2] and linked to the 3' and 5' sites of the benzene ring of the tyrosine residues on TG, and on free tyrosine. Upon stimulation by the thyroid-stimulating hormone (TSH), the follicular cells reabsorb TG and proteolytically cleave the iodinated tyrosines from TG, forming T4 and T3 (in T3, one iodine is absent compared to T4), and releasing them into the blood. Deiodinase enzymes convert T4 to T3.^[3] Thyroid hormone that is secreted from the gland is about 90% T4 and about 10% T3.^[1]

Cells of the brain are a major target for the thyroid hormones T3 and T4. Thyroid hormones play a particularly crucial role in brain development during pregnancy.^[4] A transport protein (OATP1C1) has been identified that seems to be important for T4 transport across the blood brain barrier.^[5] A second transport protein (MCT8) is important for T3 transport across brain cell membranes.^[5]

In the blood, T4 and T3 are partially bound to thyroxine-binding globulin, transthyretin and albumin. Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. Only the free fraction has hormonal activity. As with the steroid hormones and retinoic acid, thyroid hormones cross the cell membrane and bind to intracellular receptors (α₁, α₂, β₁ and β₂), which act alone, in pairs or together with the retinoid X-receptor as transcription factors to modulate DNA transcription[1].

[edit] T3 and T4 regulation

The production of thyroxine and triiodothyronine is regulated by thyroid-stimulating hormone (TSH), released by the anterior pituitary. The thyroid and thyrotropes form a negative feedback loop: TSH production is suppressed when the T4 levels are high, and vice versa. The TSH production itself is modulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus and secreted at an increased rate in situations such as cold (in which an accelerated metabolism would generate more heat). TSH production is blunted by somatostatin (SRIH), rising levels of glucocorticoids and sex hormones (estrogen and testosterone), and excessively high blood iodide concentration.

[edit] Calcitonin

An additional hormone produced by the thyroid contributes to the regulation of blood calcium levels. Parafollicular cells produce calcitonin in response to hypercalcemia. Calcitonin stimulates movement of calcium into bone, in opposition to the effects of parathyroid hormone (PTH). However, calcitonin seems far less essential than PTH, as calcium metabolism remains clinically normal after removal of the thyroid, but not the parathyroids.

It may be used diagnostically as a tumor marker for a form of thyroid cancer (medullary thyroid adenocarcinoma), in which high calcitonin levels may be present and elevated levels after surgery may indicate recurrence. It may even be used on biopsy samples from suspicious lesions (e.g. swollen lymph nodes) to establish whether they are metastasis of the original cancer.

Calcitonin can be used therapeutically for the treatment of hypercalcemia or osteoporosis.

[edit] Significance of iodine

In areas of the world where iodine (essential for the production of thyroxine, which contains four iodine atoms) is lacking in the diet, the thyroid gland can be considerably enlarged, resulting in the swollen necks of endemic goitre.

Thyroxine is critical to the regulation of metabolism and growth throughout the animal kingdom. Among amphibians, for example, administering a thyroid-blocking agent such as propylthiouracil (PTU) can prevent tadpoles from metamorphosing into frogs; conversely, administering thyroxine will trigger metamorphosis.

In humans, children born with thyroid hormone deficiency will have physical growth and development problems, and brain development can also be severely impaired, in the condition referred to as cretinism. Newborn children in many developed countries are now routinely tested for thyroid hormone deficiency as part of newborn screening by analysis of a drop of blood. Children with thyroid hormone deficiency are treated by supplementation with synthetic thyroxine, which enables them to grow and develop normally.

Because of the thyroid's selective uptake and concentration of what is a fairly rare element, it is sensitive to the effects of various radioactive isotopes of iodine produced by nuclear fission. In the event of large accidental releases of such material into the environment, the uptake of radioactive iodine isotopes by the thyroid can, in theory, be blocked by saturating the uptake mechanism with a large surplus of non-radioactive iodine, taken in the form of potassium iodide tablets. While biological researchers making compounds labelled with iodine isotopes do this, in the wider world such preventive measures are usually not stockpiled before an accident, nor are they distributed adequately afterward. One consequence of the Chernobyl disaster was an increase in thyroid cancers in children in the years following the accident. [2]

The use of iodised salt is an efficient way to add iodine to the diet. It has eliminated endemic cretinism in most developed countries, and some governments have made the iodination of flour mandatory. Potassium iodide and Sodium iodide are the most active forms of supplemental iodine.

[edit] Diseases

[edit] Hyper- and hypofunction (affects about 2% of the population)

• Hypothyroidism (underactivity)
  • Hashimoto's thyroiditis / thyroiditis
  • Ord's thyroiditis
  • Postoperative hypothyroidism
  • Postpartum thyroiditis
  • Silent thyroiditis
  • Acute thyroiditis
  • Iatrogenic hypothyroidism
• Hyperthyroidism (overactivity)
  • Thyroid storm
  • Graves-Basedow disease
  • Toxic thyroid nodule
  • Toxic nodular struma (Plummer's disease)
  • Hashitoxicosis
  • Iatrogenic hyperthyroidism
  • De Quervain thyroiditis (inflammation starting as hyperthyroidism, can end as hypothyroidism)

[edit] Anatomical problems

• Goitre
  • Endemic goitre
  • Diffuse goitre
  • Multinodular goitre
• Lingual thyroid
• Thyroglossal duct cyst

[edit] Tumors

• Thyroid adenoma
• Thyroid cancer
  • Papillary
  • Follicular
  • Medullary
  • Anaplastic
• Lymphomas and metastasis from elsewhere (rare)

[edit] Deficiencies

• Cretinism

Medication linked to thyroid disease includes amiodarone, lithium salts, some types of interferon and IL-2.

[edit] Diagnosis

[edit] Blood tests

• The measurement of thyroid-stimulating hormone (TSH) levels is often used by doctors as a screening test. Elevated TSH levels can signify an inadequate hormone production, while suppressed levels can point at excessive unregulated production of hormone.
• If TSH is abnormal, decreased levels of thyroid hormones T4 and T3 may be present; these may be determined to confirm this.
• Autoantibodies may be detected in various disease states (anti-TG, anti-TPO, TSH receptor stimulating antibodies).
• There are two cancer markers for thyroid derived cancers. Thyroglobulin (TG) for well differentiated papillary or follcular adenocarcinoma, and the rare medullary thyroid cancer has calcitonin as the marker.
• Very infrequently, TBG and transthyretin levels may be abnormal; these are not routinely tested.

[edit] Ultrasound

Nodules of the thyroid may or may not be cancer. Medical ultrasonography can help determine their nature because some of the characteristics of benign and malignant nodules differ. The main characteristics of a thyroid nodule on high frequency thyroid ultrasound are as follows:

Possible cancer	Benign characteristics
irregular border	smooth borders
hypoechoic (less echogenic than the surrounding tissue)	hyperechoic
microcalcifications	-
taller than wide shape on transverse study	-
significant intranodular blood flow by power Doppler	-
-	"comet tail" artifact as sound waves bounce off intranodular colloid

Ultrasonography is not always able to separate benign from malignant nodules with complete certainty. In suspicious cases, a tissue sample is often obtained by biopsy for microscopic examination.

[edit] Radioiodine scanning and uptake

Thyroid scintigraphy, imaging of the thyroid with the aid of radioactive iodine, usually iodine-123 (¹²³I), is performed in the nuclear medicine department of a hospital or clinic. Radioiodine collects in the thyroid gland before being excreted in the urine. While in the thyroid the radioactive emissions can be detected by a camera, producing a rough image of the shape (a radiodine scan) and tissue activity (a radioiodine uptake) of the thyroid gland.

A normal radioiodine scan shows even uptake and activity throughout the gland. Irregularity can reflect an abnormally shaped or abnormally located gland, or it can indicate that a portion of the gland is overactive or underactive, different from the rest. For example, a nodule that is overactive ("hot") to the point of suppressing the activity of the rest of the gland is usually a thyrotoxic adenoma, a surgically curable form of hyperthyroidism that is hardly ever malignant. In contrast, finding that a substantial section of the thyroid is inactive ("cold") may indicate an area of non-functioning tissue such as thyroid cancer.

The amount of radioactivity can be counted as an indicator of the metabolic activity of the gland. A normal quantitation of radioiodine uptake demonstrates that about 8 to 35% of the administered dose can be detected in the thyroid 24 hours later. Overactivity or underactivity of the gland as may occur with hypothyroidism or hyperthyroidism is usually reflected in decreased or increased radioiondine uptake. Different patterns may occur with different causes of hypo- or hyperthyroidism.

[edit] Biopsy

A medical biopsy refers to the obtaining of a tissue sample for examination under the microscope or other testing, usually to distinguish cancer from noncancerous conditions. Thyroid tissue may be obtained for biopsy by fine needle aspiration or by surgery.

Needle aspiration has the advantage of being a brief, safe, outpatient procedure that is safer and less expensive than surgery and does not leave a visible scar. Needle biopsies became widely used in the 1980s, but it was recognized that accuracy of identification of cancer was good but not perfect. The accuracy of the diagnosis depends on obtaining tissue from all of the suspicious areas of an abnormal thyroid gland. The reliability of needle aspiration is increased when sampling can be guided by ultrasound, and over the last 15 years, this has become the preferred method for thyroid biopsy in North America.

[edit] Treatment

[edit] Medical treatment

Levothyroxine is a stereoisomer of thyroxine which is degraded much slower and can be administered once daily in patients with hypothyroidism.

Graves' disease may be treated with the thioamide drugs propylthiouracil, carbimazole or methimazole, or rarely with Lugol's solution. Hyperthyroidism as well as thyroid tumors may be treated with radioactive iodine.

Percutaneous Ethanol Injections, PEI, for therapy of recurrent thyroid cysts, and metastatic thyroid cancer lymph nodes, as an alternative to the usual surgical method.

[edit] Surgery

Thyroid surgery is performed for a variety of reasons. A nodule or lobe of the thyroid is sometimes removed for biopsy or for the presence of an autonomously functioning adenoma causing hyperthyroidism. A large majority of the thyroid may be removed, a subtotal thyroidectomy, to treat the hyperthyroidism of Graves' disease, or to remove a goitre that is unsightly or impinges on vital structures. A complete thyroidectomy of the entire thyroid, including associated lymph nodes, is the preferred treatment for thyroid cancer. Removal of the bulk of the thyroid gland usually produces hypothyroidism, unless the person takes thyroid hormone replacement.

If the thyroid gland must be removed surgically, care must be taken to avoid damage to adjacent structures, the parathyroid glands and the recurrent laryngeal nerve. Both are susceptible to accidental removal and/or injury during thyroid surgery. The parathyroid glands produce parathyroid hormone (PTH), a hormone needed to maintain adequate amounts of calcium in the blood. Removal results in hypoparathyroidism and a need for supplemental calcium and vitamin D each day. The recurrent laryngeal nerves provide motor control for all external muscles of the larynx except for the cricothyroid muscle, also runs along the posterior thyroid. Accidental laceration of either of the two or both recurrent laryngeal nerves may cause paralysis of the vocal cords and their associated muscles, changing the voice quality.

[edit] Radioiodine therapy

Large goiters that cause symptoms, but do not harbor cancer, after evaluation, and biopsy of suspicious nodules can be treated by an alternative therapy with radioiodine. The iodine uptake can be high in countries with iodine deficiency, but low in iodine sufficient countries. The 1999 release of rhTSH thyrogen in the USA, can boost the uptakes to 50-60% allowing the therapy with iodine 131. The gland shrinks by 50-60%, but can cause hypothyroidism, and rarely pain syndrome cause by radiation thyroiditis that is short lived and treated by steroids.

[edit] History

There are several findings that evidence a great interest for thyroid disorders just in the Medieval Medical School of Salerno (XII Century). Rogerius Salernitanus, the Salernitan surgeon and author of "Post mundi fabricam" (around 1180) was considered at that time the surgical text par excellence all over Europe. In the chapter "De bocio" of his magnus opum he describes several pharmacological and surgical cures, some of which nowadays are reappraised quite scientifically effective.^[6]

In modern times, the thyroid was first identified by the anatomist Thomas Wharton (whose name is also eponymised in Wharton's duct of the submandibular gland) in 1656.^[7]

Thyroid hormone (or thyroxin) was only identified in the 19th century.

[edit] Additional images

	Section of the neck at about the level of the sixth cervical vertebra.	Muscles of the neck. Anterior view.	The arch of the aorta, and its branches.
Superficial dissection of the right side of the neck, showing the carotid and subclavian arteries.	Diagram showing common arrangement of thyroid veins.	Sagittal section of nose mouth, pharynx, and larynx.	Muscles of the pharynx, viewed from behind, together with the associated vessels and nerves.
The position and relation of the esophagus in the cervical region and in the posterior mediastinum. Seen from behind.	Section of thyroid gland of sheep. X 160.	The thymus of a full-term fetus, exposed in situ.	Thyoid histology

Transfer RNA

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Transfer RNA

Transfer RNA (abbreviated tRNA), first hypothesized by Francis Crick, is a small RNA chain (73-93 nucleotides) that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation. It has a 3' terminal site for amino acid attachment. This covalent linkage is catalyzed by an aminoacyl tRNA synthetase. It also contains a three base region called the anticodon that can base pair to the corresponding three base codon region on mRNA. Each type of tRNA molecule can be attached to only one type of amino acid, but because the genetic code contains multiple codons that specify the same amino acid, tRNA molecules bearing different anticodons may also carry the same amino acid.

Contents [hide] 1 Structure 2 Anticodon 3 Aminoacylation 4 tRNA genes 5 History 6 References 7 See also 8 External links

[edit] Structure

Structure of tRNA. CCA tail in orange, Acceptor stem in purple, D arm in red, Anticodon arm in blue with Anticodon in black, T arm in green.

tRNA has primary structure, secondary structure (usually visualized as the cloverleaf structure), and tertiary structure (all tRNAs have a similar L-shaped 3D structure that allows them to fit into the P and A sites of the ribosome).

1. The 5'-terminal phosphate group.
2. The acceptor stem is a 7-bp stem made by the base pairing of the 5'-terminal nucleotide with the 3'-terminal nucleotide (which contains the CCA 3'-terminal group used to attach the amino acid). The acceptor stem may contain non-Watson-Crick base pairs.
3. The CCA tail is a CCA sequence at the 3' end of the tRNA molecule. This sequence is important for the recognition of tRNA by enzymes critical in translation. In prokaryotes, the CCA sequence is transcribed. In eukaryotes, the CCA sequence is added during processing and therefore does not appear in the tRNA gene.
4. The D arm is a 4 bp stem ending in a loop that often contains dihydrouridine.
5. The anticodon arm is a 5-bp stem whose loop contains the anticodon.
6. The T arm is a 5 bp stem containing the sequence TΨC where Ψ is a pseudouridine.
7. Bases that have been modified, especially by methylation, occur in several positions outside the anticodon. The first anticodon base is sometimes modified to inosine (derived from adenine) or pseudouridine (derived from uracil).

[edit] Anticodon

An anticodon ^[1] is a unit made up of three nucleotides that correspond to the three bases of the codon on the mRNA. Each tRNA contains a specific anticodon triplet sequence that can base-pair to one or more codons for an amino acid. For example, one codon for lysine is AAA; the anticodon of a lysine tRNA might be UUU. Some anticodons can pair with more than one codon due to a phenomenon known as wobble base pairing. Frequently, the first nucleotide of the anticodon is one of two not found on mRNA: inosine and pseudouridine, which can hydrogen bond to more than one base in the corresponding codon position. In the genetic code, it is common for a single amino acid to occupy all four third-position possibilities; for example, the amino acid glycine is coded for by the codon sequences GGU, GGC, GGA, and GGG.

To provide a one-to-one correspondence between tRNA molecules and codons that specify amino acids, 61 tRNA molecules would be required per cell. However, many cells contain fewer than 61 types of tRNAs because the wobble base is capable of binding to several, though not necessarily all, of the codons that specify a particular amino acid^[2].

[edit] Aminoacylation

Aminoacylation is the process of adding an aminoacyl group to a compound. It produces tRNA molecules with their CCA 3' ends covalently linked to an amino acid.

Each tRNA is aminoacylated (or charged) with a specific amino acid by an aminoacyl tRNA synthetase. There is normally a single aminoacyl tRNA synthetase for each amino acid, despite the fact that there can be more than one tRNA, and more than one anticodon, for an amino acid. Recognition of the appropriate tRNA by the synthetases is not mediated solely by the anticodon, and the acceptor stem often plays a prominent role.

Reaction:

1. amino acid + ATP → aminoacyl-AMP + PPi
2. aminoacyl-AMP + tRNA → aminoacyl-tRNA + AMP

[edit] tRNA genes

Organisms vary in the number of tRNA genes in their genome. The nematode worm C. elegans, a commonly used model organism in genetics studies, has 19,000 genes in its nuclear genome, of which 659 code for tRNA^[3]. The budding yeast Saccharomyces cerevisiae has 275 tRNA genes in its genome. In the human genome, which according to current estimates has about 25,000 genes in total, there are about 2000 non-coding RNA genes, which include tRNA genes. There are 22 mitochondrial tRNA genes^[4]; 497 nuclear genes encoding cytoplasmic tRNA molecules and there are 324 tRNA-derived putative pseudogenes.^[5]

Cytoplasmic tRNA genes can be grouped into 49 families according to their anticodon features. These genes are found on all chromosomes, except 22 and Y chromosome. High clustering on 6p is observed (140 tRNA genes), as well on 1 chromosome.^[5]

tRNA molecules are transcribed (in eukaryotic cells) by RNA polymerase III, unlike messenger RNA which is transcribed by RNA polymerase II.

[edit] History

Significant research on structure was conducted in the early 1960s by Alex Rich and Don Caspar, two researchers in Boston, the Jacques Fresco group in Princeton University and a United Kingdom group at King's College London.^[6] A later publication reported the primary structure in 1965 by Robert W. Holley. The secondary and tertiary structures were derived from X-ray crystallography studies reported independently in 1974 by American and British research groups headed, respectively, by Alexander Rich and Aaron Klug.

[edit] References

1. ^ Felsenfeld G, Cantoni G. "Use of thermal denaturation studies to investigate the base sequence of yeast serine sRNA". Proc Natl Acad Sci U S A 51: 818-26. PMID 14172997.
2. ^ Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. (2004). Molecular Biology of the Cell. WH Freeman: New York, NY. 5th ed.
3. ^ Hartwell LH, Hood L, Goldberg ML, Reynolds AE, Silver LM, Veres RC. (2004). Genetics: From Genes to Genomes 2nd ed. McGraw-Hill: New York, NY. p 264.
4. ^ Ibid. p 529.
5. ^ ^{a b} Lander E. et al. (2001). "Initial sequencing and analysis of the human genome". Nature 409 (6822): 860-921. PMID 11237011.
6. ^ Brian F.C. Clark (October 2006). "The crystal structure of tRNA". J. Biosci. 31 (4): 453-7. PMID 17206065.

[edit] See also

• mRNA
• tmRNA
• non-coding RNA and introns
• translation

[edit] External links

• tRNA could be the cause of heart attack
• Sprinzl tRNA compilation
• Collection of tRNAs identified from complete genomes
• Molecule of the Month © RCSB Protein Data Bank:
  • Transfer RNA
  • Aminoacyl-tRNA Synthetases
  • Elongation Factors

v • d • e Major families of biochemicals
Peptides | Amino acids | Nucleic acids | Carbohydrates | Lipids | Terpenes | Carotenoids | Tetrapyrroles | Enzyme cofactors | Steroids | Flavonoids | Alkaloids | Polyketides | Glycosides
Analogues of nucleic acids:	Types of Nucleic Acids	Analogues of nucleic acids:
Nucleobases:	Purine (Adenine, Guanine) | Pyrimidine (Uracil, Thymine, Cytosine)
Nucleosides:	Adenosine/Deoxyadenosine | Guanosine/Deoxyguanosine | Uridine | Thymidine | Cytidine/Deoxycytidine
Nucleotides:	monophosphates (AMP, UMP, GMP, CMP) | diphosphates (ADP, UDP, GDP, CDP) | triphosphates (ATP, UTP, GTP, CTP, GTPgammaS) | cyclic (cAMP, cGMP, cADPR)
Deoxynucleotides:	monophosphates (dAMP, TMP, dGMP, dCMP) | diphosphates (dADP, TDP, dGDP, dCDP) | triphosphates (dATP, TTP, dGTP, dCTP)
Ribonucleic acids:	RNA | mRNA | piRNA | tRNA | rRNA | ncRNA | gRNA | shRNA | siRNA | snRNA | miRNA | snoRNA
Deoxyribonucleic acids:	DNA | mtDNA | cDNA | plasmid | Cosmid | BAC | YAC | HAC
Analogues of nucleic acids:	GNA | PNA | TNA | Morpholino | LNA

Retrieved from "http://en.wikipedia.org/wiki/Transfer_RNA"

Categories: RNA | Protein biosynthesis | Non-coding RNA