Thyroid

The thyroid gland and its relations

thumb

The thyroid (from the Greek word for "shield", after its shape) is one of the larger endocrine glands in the body. It is a double-lobed structure located in the neck and produces hormones, principally thyroxine (T₄) and triiodothyronine (T₃), that regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. The hormone calcitonin is also produced and controls calcium blood levels. Iodine is necessary for the production of both hormones. Hyperthyroidism (overactive thyroid) and hypothyroidism (underactive thyroid) are the most common problems of the thyroid gland.

Anatomy

The thyroid is situated on the front side of the neck, at the level of C5 to T1 vertebral bodies, just below the laryngeal prominence (Adam's apple), near the thyroid cartilage over the trachea but covered by layers of skin and muscle. 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. It may enlarge substantially during pregnancy and when affected by a variety of diseases.

Blood supply

The thyroid gland is supplied by two pairs of arteries: the superior and inferior thyroid arteries of each side. The superior thyroid artery is the first branch of the external carotid, and supplies mostly the upper half of the thyroid gland, while the inferior thyroid artery is the major branch of the thyrocervical trunk, which comes off of the subclavian artery. In 10% of people, there is an additional thyroid artery, the thyreoidea ima, that arises from the brachiocephalic trunk or the arch of the aorta. Lymph drainage follows the arterial supply.

There are three main veins that drain the thyroid to the superior vena cava: the superior, middle and inferior thyroid veins.

In comparison to the other organs of the body, the Thyroid receives one of the largest blood supplies per gram weight. The largest blood supply is seen in the Carotid arch baroreceptor organ.

Embryologic development

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 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.

Histology of the thyroid

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

Physiology

The primary function of the thyroid is production of the hormones thyroxine (T4), triiodothyronine (T3), and calcitonin. Up to 40% 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 T4The thyroid gland in Endocrinology: An Integrated Approach by Stephen Nussey and Saffron Whitehead (2001) Published by BIOS Scientific Publishers Ltd. ISBN 1859962521..

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, captured with the "iodine trap" is activated 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 TSH (see below), 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. 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 thyroid hormone. A transport protein (OATP1C1) has been identified that seems to be important for T4 transport across the blood brain barrier"Thyroid hormone transporters in health and disease" by Jurgen Jansen, Edith C. H. Friesema, Carmelina Milici and Theo J. Visser in Thyroid (2005) Volume 15, pages 757-768. PMID 16131319.. 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 (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].

T3 and T4 regulation

The production of thyroxine is regulated by thyroid-stimulating hormone (TSH), released by the 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, 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).

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. However calcitonin seems far less essential than PTH, as calcium metabolism remains clinically normal after removal of the thyroid, but not the parathyroids.

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

The 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.

Diseases of the thyroid gland

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)

Anatomical problems:
* Goitre
** Endemic goitre
** Diffuse goitre
** Multinodular goitre
* Lingual thyroid
* Thryoglossal duct cyst

Tumors:
* Thyroid adenoma
* Thyroid cancer
** Papillary
** Follicular
** Medullary
** Anaplastic
* Lymphomas and metastasis from elsewhere (rare)

Deficiencies:
*Cretinism

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

Diagnosis

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.

Nodules of the thyroid may require medical ultrasonography to establish their nature.The main characteristics of a thyroid nodule on high frequency thyroid ultrasound that suggest possible cancer are: 1.irregular border 2. hypoechoic ( less echogenic than the surrounding tissue).3. microcalcifications 4. taller than wide shape on transverse study.5. significant intranodular blood flow by power Doppler. Benign characteristics include 1. hyperechoic 2. smooth borders 3. "comet tail" artifact as sound waves bounce off intranodular colloid. However, these criteria alone can help select nodules for biopsy, but no criteria is 100%. The ideal way to assure that a nodule is not cancerous is a biopsy. To be sure you have sampled the specific nodule of interest, even if you can not feel it, ultrasound guided fine needle aspiration is recommended. Free hand fine needle aspiration (FNA) may be performed, on palpable nodules, but has a higher error rate, or inadequate sample result. If a result is not conclusive, thyroid scintigraphy with iodine-123 may reveal whether the nodule is abnormally active "hot or inactive "cold". Hot nodules are very, very rarely cancerous, therefore the endocrinologist may not need to repeat the biopsy. However if it is not hot, an inconclusive FNA result may warrant a repeat biopsy, but this time, not by free hand, but by ultrasound guided FNA technique.

Treatment

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.

Thyroid 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.

Thyroid: Encyclopedia BETA

Contents