Everything about the Thyroid totally explained
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 (also known as 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 (T
4) and
triiodothyronine (T
3). 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 T
3 and T
4. 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 the shape of the related thyroid cartilage.
Hyperthyroidism (overactive thyroid) and
hypothyroidism (underactive thyroid) are the most common problems of the thyroid gland.
Anatomy
The thyroid gland is a butterfly-shaped organ and is composed of two cone-like lobes or wings:
lobus dexter (right lobe) and
lobus sinister (left lobe), connected with the
isthmus. The organ is situated on the anterior side of the neck, lying against and around the
larynx and
trachea, reaching posteriorly the
oesophagus and
carotid sheath. It starts cranially at the oblique line on the
thyroid cartilage (just below the laryngeal prominence or
Adam's apple) and extends inferiorly to the fourth to sixth
tracheal ring. It is difficult to demarcate the gland's upper and lower border with vertebral levels as it moves position in relation to these during swallowing.
The thyroid gland is covered by a fibrous sheath, the
capsula glandulae thyroidea, composed of an internal and external layer. The external layer is anteriorly continuous with the
lamina pretrachealis fasciae cervicalis and posteriorolaterally continuous with the
carotid sheath. The gland is covered anteriorly with
infrahyoid muscles and laterally with the
sternocleidomastoid muscle. Posteriorly, the gland is fixed to the
cricoid and
tracheal cartilage and
cricopharyngeus muscle by a thickening of the fascia to form the
posterior suspensory ligament of Berry. In variable extent,
Zuckerkandl's tubercle, a pyramidal extension of the thyroid lobe, is present at the most posterior side of the lobe. In this region the
recurrent laryngeal nerve and the inferior thyroid artery pass next to or in the ligament and tubercle. Between the two layers of the capsule and on the posterior side of the lobes there are on each side two
parathyroid glands.
The
thyroid isthmus is variable in presence and size, and can encompass a cranially extending pyramid lobe (
lobus pyramidalis or
processus pyramidalis), remnant of the
thyroglossal duct. The thyroid is one of the larger endocrine glands, weighing 2-3 grams in neonates and 18-60 grams in adults, and is increased in pregnancy.
The thyroid is supplied with arterial blood from the
superior thyroid artery, a branch of the
external carotid artery, and the
inferior thyroid artery, a branch of the
thyrocervical trunk, and sometimes by the
thyroid ima artery, branching directly from the aortic arch. The venous blood is drained via
superior thyroid veins, draining in the
internal jugular vein, and via
inferior thyroid veins, draining via the
plexus thyroideus impar in the left
brachiocephalic vein.
Lymphatic drainage passes frequently the
lateral deep cervical lymph nodes and the
pre- and parathracheal lymph nodes. The gland is supplied by
sympathetic nerve input from the
superior cervical ganglion and the
cervicothoracic ganglion of the
sympathetic trunk, and by
parasympathetic nerve input from the
superior laryngeal nerve and the
recurrent laryngeal nerve.
Embryological 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 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.
Histology
At the microscopic 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. |
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.
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's secreted from the gland is about 90% T4 and about 10% T3. 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.
Anatomical problems
Goitre
Lingual thyroid
Thyroglossal 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
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.
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 isn't 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.
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's 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's 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 radioiodine uptake. Different patterns may occur with different causes of hypo- or hyperthyroidism.
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's safer and less expensive than surgery and doesn't 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.
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.
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's 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. Consequently, individuals who have undergone a total thyroidectomy are typically placed on thyroid hormone replacement for the remainder of their lives. Higher than normal doses are often administered to prevent recurrence.
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. In the event the blood supply to any one of the parathyroid glands is endangered through surgery, the parathyroid gland(s) involved may be re-implanted in surrounding muscle tissue. 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.
Radioiodine therapy
Large goiters that cause symptoms, but don't 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's short lived and treated by steroids.
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.
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.
Thyroid hormone (or thyroxin) was identified only in the 19th century.
Additional images
Image:Illu endocrine system.jpg|Position of the Thyroid in Males and Females
Image:illu08_thyroid.jpg|
Image:Gray384.png|Section of the neck at about the level of the sixth cervical vertebra.
Image:Gray386.png|Muscles of the neck. Anterior view.
Image:Gray505.png|The arch of the aorta, and its branches.
Image:Gray507.png|Superficial dissection of the right side of the neck, showing the carotid and subclavian arteries.
Image:Gray561.png|Diagram showing common arrangement of thyroid veins.
Image:Gray994.png|Sagittal section of nose mouth, pharynx, and larynx.
Image:Gray1031.png|Muscles of the pharynx, viewed from behind, together with the associated vessels and nerves.
Image:Gray1032.png|The position and relation of the esophagus in the cervical region and in the posterior mediastinum. Seen from behind.
Image:Gray1176.png|Section of thyroid gland of sheep. X 160.
Image:Gray1178.png|The thymus of a full-term fetus, exposed in situ.
Image:Thyoid-histology.jpg|Thyoid histology
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