The thyroid is one of the largest endocrine glands in the body. This gland is found in the neck inferior to (below) the thyroid cartilage (a.k.a. the Adam's apple in men) and at approximately the same level as the cricoid cartilage. 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.
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. 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) 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. Thyroid hormone that is secreted from the gland is about 90% T4 and about 10% T3.
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. A transport protein (OATP1C1) has been identified that seems to be important for T4 transport across the blood brain barrier. A second transport protein (MCT8) is important for T3 transport across brain cell membranes.
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 (€ á1, € á2, € â1 and € â2), which act alone, in pairs or together with the retinoid X-receptor as transcription factors to modulate DNA transcription.
T3 and T4 regulation
The production of thyroxine and triiodothyronine is regulated by thyroid-stimulating hormone (TSH), released by the anterior pituitary (that is in turn released as a result of TRH release by the hypothalamus). 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.
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.
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.
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.
Hyper- and hypofunction (affects about 2% of the population)
Hypothyroidism is the disease state in humans and animals caused by insufficient production of thyroid hormone by the thyroid gland.
There are several distinct causes for chronic hypothyroidism. Historically, and still in many developing countries, iodine deficiency is the most common cause of hypothyroidism worldwide. In present day developed countries, however, hypothyroidism is mostly caused by Hashimoto's thyroiditis, or by a lack of the thyroid gland or a deficiency of hormones from either the hypothalamus or the pituitary.
Hypothyroidism can result from postpartum thyroiditis, a condition that affects about 5% of all women within a year after giving birth. The first phase is typically hyperthyroidism. Then, the thyroid either returns to normal or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, one in five will develop permanent hypothyroidism requiring life-long treatment.
Hypothyroidism can also result from sporadic inheritance, sometimes autosomal recessive.
Hypothyroidism is also a relatively common hormone disease in domestic dogs, with some specific breeds having a definite predisposition.
Temporary hypothyroidism can be due to the Wolff-Chaikoff effect.
Hypothyroidism is often classified by the organ of origin Symptoms Adults
In adults, hypothyroidism is associated with the following symptoms:
- Poor muscle tone (muscle hypotonia)
- Cold intolerance, increased sensitivity to cold
- Weight gain
- Muscle cramps and joint pain
- Thin, brittle fingernails
- Thin, brittle hair
- Dry, itchy skin -
- Slowed speech and a hoarse, breaking voice. Deepening of the voice can also be noticed.
- Dry puffy skin, especially on the face
- Thinning of the outer third of the eyebrows
- Abnormal menstrual cycles
- Low basal body temperature
Hyperthyroidism is the term for overactive tissue within the thyroid gland, resulting in overproduction and thus an excess of circulating free thyroid hormones: thyroxine (T4), triiodothyronine (T3), or both. The term is also often used more loosely to describe any syndrome of excess thyroid hormone (more properly termed hyperthyroxinemia), regardless of the source.
Thyrotoxicosisis the term for symptomomatic hyperthyroxinemia. Thyroid hormone is important at a cellular level, affecting nearly every type of tissue in the body. It functions as a stimulus to metabolism, and is critical to normal function of the cell. In excess it overstimulates, causing "speeding up" of various body systems, and thus symptoms: Fast heart beat results in palpitations, a fast nervous system in tremor and anxiety symptoms, a fast digestive system in weight loss and diarrhoea. Lack of functioning thyroid tissue results in a symptomatic lack of thyroid hormone, termed hypothyroidism.
Signs and symptoms
Major clinical signs include weight loss (often accompanied by a ravenous appetite), anxiety, intolerance to heat, fatigue, hair loss, weakness, hyperactivity, irritability, apathy, depression, polyuria, polydipsia, and sweating. Additionally, patients may present with a variety of symptoms such as palpitations and arrhythmias (notably atrial fibrillation), shortness of breath (dyspnea), loss of libido, nausea, vomiting, osteoporosis and diarrhea. In the elderly, these classical symptoms may not be present and they may present only with fatigue and weight loss leading to apathetic hyperthyroidism. Thyrotoxic crisis comes when the sick person is having stress. Its symptoms are increase of body temperature to over 40 degrees Celsius, tachycardia, arrhythmia, vomiting, diarrhea, dehydration, icterus, coma and death.
The major and generally accepted modalities for treatment of hyperthyroidism in humans involve initial temporary use of suppressive thyrostatics medication, and possibly later use of permanent surgical or radioisotope therapy. All approaches may cause under active thyroid function (hypothyroidism) which is easily managed with levothyroxine supplementation.
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