In vertebrate anatomy, the thyroid gland or simply, the thyroid, is one of the l

argest endocrine glands in the body, and is not to be confused with the "parathy
roid glands" (a completely different set of glands). The thyroid gland is found
in the neck, inferior to (below) the thyroid cartilage (also known as the 'Adam'
s Apple') and at approximately the same level as the cricoid cartilage. The thyr
oid controls how quickly the body uses energy, makes proteins, and controls how
sensitive the body should be to other hormones.
The thyroid gland participates in these processes by producing thyroid hormones,
the principal ones being triiodothyronine (T3) and thyroxine (T4). These hormon
es regulate the rate of metabolism and affect the growth and rate of function of
many other systems in the body. T3 and T4 are synthesized utilizing both iodine
and tyrosine. The thyroid gland also produces a hormone called 'calcitonin', wh
ich plays a role in calcium homeostasis.
The thyroid gland is controlled by the hypothalamus and pituitary (to be specifi
c, the anterior pituitary). The thyroid gland gets its name from the Greek word
for "shield", after the shape of the related thyroid cartilage. The most common
problems of the thyroid gland consist of an over-active thyroid gland, referred
to as 'hyperthyroidism', and an under-active thyroid gland, referred to as 'hypo
thyroidism'.
Contents [hide]
1 Anatomy
1.1 Embryological development
1.2 Histology
2 Disorders
2.1 Hyperthyroidism
2.2 Hypothyroidism
2.3 Initial hyperthyroidism followed by hypothyroidism
2.4 Enlargement of the thyroid
2.5 Cancers
2.6 Non-cancerous nodules
2.7 Seasonal Aggravation
3 Physiology
3.1 T3 and T4 production and action
3.2 T3 and T4 regulation
3.3 Thyroid function laboratory tests - normal ranges[20]
3.4 Significance of iodine
4 Treatment for Hyperthyroidism
5 History
6 In other animals
7 Additional images
8 See also
9 References
10 External links
[edit] Anatomy
The thyroid gland is a butterfly-shape organ and is composed of two cone-like lo
bes or wings, lobus dexter (right lobe) and lobus sinister (left lobe), connecte
d via 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 carti
lage (just below the laryngeal prominence, or 'Adam's Apple'), and extends infer
iorly to approximately the fifth or sixth tracheal ring.[1] It is difficult to d
emarcate the gland's upper and lower border with vertebral levels because it mov
es position in relation to these during swallowing.
The thyroid gland is covered by a fibrous sheath, the capsula glandulae thyroide
a, composed of an internal and external layer. The external layer is anteriorly
continuous with the lamina pretrachealis fasciae cervicalis and posteriorolatera
lly continuous with the carotid sheath. The gland is covered anteriorly with inf
rahyoid muscles and laterally with the sternocleidomastoid muscle also known as
sternomastoid muscle. On the posterior side, the gland is fixed to the cricoid a
nd tracheal cartilage and cricopharyngeus muscle by a thickening of the fascia t
o form the posterior suspensory ligament of Berry.[2][3] The thyroid gland's fir
m attachment to the underlying trachea is the reason behind its movement with sw
allowing.[4] In variable extent, Lalouette's Pyramid, a pyramidal extension of t
he thyroid lobe, is present at the most anterior side of the lobe. In this regio
n, 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, th
ere are on each side two parathyroid glands.
The thyroid isthmus is variable in presence and size, and can encompass a crania
lly extending pyramid lobe (lobus pyramidalis or processus pyramidalis), remnant
of the thyroglossal duct. The thyroid is one of the larger endocrine glands, we
ighing 2-3 grams in neonates and 18-60 grams in adults, and is increased in preg
nancy.
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 brachiocephalic trunk. The venous blood is drained via superio
r thyroid veins, draining in the internal jugular vein, and via inferior thyroid
veins, draining via the plexus thyroideus impar in the left brachiocephalic vei
n.
Lymphatic drainage passes frequently the lateral deep cervical lymph nodes and t
he pre- and parathracheal lymph nodes. The gland is supplied by parasympathetic
nerve input from the superior laryngeal nerve and the recurrent laryngeal nerve.
[edit] Embryological development
In the fetus, at 3 4 weeks of gestation, the thyroid gland appears as an epithelia
l proliferation in the floor of the pharynx at the base of the tongue between th
e tuberculum impar and the copula linguae at a point latter indicated by the for
amen cecum. The thyroid then descends in front of the pharyngeal gut as a bilobe
d diverticulum through the thyroglossal duct. Over the next few weeks, it migrat
es to the base of the neck. During migration, the thyroid remains connected to t
he tongue by a narrow canal, the thyroglossal duct.
Thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) start
being secreted from the fetal hypothalamus and pituitary at 18-20 weeks of gesta
tion, and fetal production of thyroxine (T4) reach a clinically significant leve
l at 18 20 weeks.[5] Fetal triiodothyronine (T3) remains low (less than 15 ng/dL)
until 30 weeks of gestation, and increases to 50 ng/dL at term.[5] Fetal self-su
fficiency of thyroid hormones protects the fetus against e.g. brain development
abnormalities caused by maternal hypothyroidism.[6] However, preterm births can
suffer neurodevelopmental disorders due to lack of maternal thyroid hormones due
their own thyroid being insufficiently developed to meet their postnatal needs.
[7]
The portion of the thyroid containing the parafollicular C cells, those responsi
ble for the production of calcitonin, are derived from the 4th pharyngeal pouch
endoderm. This is first seen as the ultimobranchial body, which joins the primor
dial thyroid gland during its descent to its final location in the anterior neck
.
[edit] Histology
At the microscopic level, there are three primary features of the thyroid:[8]
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. Insi
de the follicles, colloid serve as a reservoir of materials for thyroid hormone
production and, to a lesser extent, act as a reservoir for the hormones themselv
es. Colloid is rich in a protein called thyroglobulin.
Thyroid epithelial cells
(or "follicular cells") The follicles are surrounded by a single layer of thyroi
d epithelial cells, which secrete T3 and T4. When the gland is not secreting T3/
T4 (inactive), the epithelial cells range from low columnar to cuboidal cells. W
hen active, the epithelial cells become tall columnar cells.
Parafollicular cells
(or "C cells") Scattered among follicular cells and in spaces between the spheri
cal follicles are another type of thyroid cell, parafollicular cells, which secr
ete calcitonin.
[edit] Disorders
Disorders of the thyroid gland fall into the following categories:
[edit] Hyperthyroidism
Hyperthyroidism in an overactive thyroid. It is the overproduction of the "thyro
id hormones" (T3 and T4) by the thyroid gland to which hyperthyroidism refers. T
he most common cause of hyperthyroidism is a disease called "Graves' Disease". G
raves' Disease is a 'diffuse toxic goiter' in which the thyroid gland enlarges a
s a result of the thyroid glands' overproduction of the T3 & T4 hormones.
Graves' disease is considered to be an autoimmune disease and is the most common
cause of thyroid gland overactivity (hyperthyroidism). Graves' disease is much
more common in women than in men. Graves' Disease results from excess stimulatio
n of the thyroid gland and usually presents with symptoms in the 2-3rd decade of
life. Symptoms include: An enlarged thyroid (goitre), protruding eyes (exopthal
mos), palpitations, excess sweating, diarrhea, weight loss, muscle weakness and
unusual sensitivity to heat. Treatment of Grave's disease involves the patient t
aking an oral dose of radioactive iodine, resulting in permanent destruction of
cells in the thyroid, thus rendering them permanently inactive. The patient may
then be treated with daily replacement hormone therapy as a result of a new foun
d hypothyroidism.
[edit] Hypothyroidism
Hypothyroidism is the underproduction of "thyroid hormones" (T3 and T4). Hypothy
roid disorders occur when the thyroid gland is inactive or underactive as a resu
lt of improper formation from birth, or the removal in whole or the removal in p
art of the thyroid gland.
Symptoms include: abnormal weight gain, tiredness, baldness, temperature intoler
ance (both heat and cold), and palpitation.
[edit] Initial hyperthyroidism followed by hypothyroidism
This is the overproduction of T3 and T4 followed by the underproduction of T3 an
d T4. There are two types: "Hashimoto's Thyroiditis" and "Postpartum Thyroiditis
".
Hashimoto's thyroiditis is an autoimmune disorder whereby the body's own immune
system reacts with the thyroid tissues. At the beginning, the gland is overactiv
e, and then becomes underactive as the gland is destroyed resulting in too littl
e thyroid hormone production or hypothyroidism. Hashimoto's is most common in mi
ddle-age females and tend to run in families. Also more common in individuals wi
th hashimoto's thyroiditis are type 1 diabetes and celiac disease.[9]
Postpartum thyroiditis occurs in some females following delivery. The gland gets
inflamed and the condition initially presents with over activity of the gland f
ollowed by under activity. In some cases, the gland does recover with time and r
esume its functions.
[edit] Enlargement of the thyroid
An enlarged thyroid gland can exist and not be considered "hyperthyroidism". The
term "Non-toxic goiter" (or simply 'Goiter') is used when enlargement of the th
yroid gland occurs - but only if the enlargement is not as a result of hyperthyr
oidism (not due to the overproduction of a thyroid hormone), nor due to a malign
ancy. Only then can the condition be deemed a "Non-toxic Goiter" (or 'Goiter') f
or short. This enlargement, the 'goiter', can occur when iodine is not in the di
et in sufficient amounts. Goiter due to iodine deficiency is uncommon in develop
ed countries as various food items come standard with added iodine (i.e., Season
ing-type table salt is supplemented with iodine). Iodine deficiency is still obs
erved in some developing parts of the world.
In addition, enlargement of the thyroid can also occur as a result of a bacteria
l infection or a viral infection. When this occurs it is deemed 'Thyroiditis'.
Goiter typically takes many years to present.
[edit] Cancers
Cancers do occur in the thyroid gland and, in general, are more common in female
s. In most cases, the thyroid cancer presents as a painless mass in the neck. It
is very unusual for the thyroid cancers to present with symptoms, unless it has
been neglected. One may be able to feel a hard nodule in the neck. Diagnosis is
made using a needle biopsy and various radiological studies. All thyroid cancer
s are treated with surgery.[10]
[edit] Non-cancerous nodules
Many individuals may find the presence of small masses (nodules) in the neck. Th
e majority of these thyroid nodules are benign (non cancerous). The presence of
a thyroid nodule does not mean one has thyroid disease. Most thyroid nodules do
not cause any symptoms, and most are discovered on an incidental exam. Doctors u
sually perform a needle aspiration biopsy of the thyroid to determine the status
of the nodules. If the nodule is found to be non-cancerous, no other treatment
is required. If the nodule is suspicious then surgery is recommended..
[edit] Seasonal Aggravation
Limited research shows that seasonal allergies may trigger episodes of hypo- or
hyperthyroidism.[11][12]
[edit] Physiology
The primary function of the thyroid is production of the hormones triiodothyroni
ne (T3), thyroxine (T4), and calcitonin. Up to 80% of the T4 is converted to T3
by peripheral organs such as the liver, kidney and spleen. T3 is several times m
ore powerful than T4, which is largely a prohormone, perhaps four[13] or even te
n times more active.[14]
[edit] T3 and T4 production and action
The system of the thyroid hormones T3 and T4.[15]Thyroxine (T4) is synthesised b
y the follicular cells from free tyrosine and on the tyrosine residues of the pr
otein called thyroglobulin (Tg). Iodine is captured with the "iodine trap" by th
e hydrogen peroxide generated by the enzyme thyroid peroxidase (TPO)[16] and lin
ked to the 3' and 5' sites of the benzene ring of the tyrosine residues on Tg, a
nd on free tyrosine. Upon stimulation by the thyroid-stimulating hormone (TSH),
the follicular cells reabsorb Tg and cleave the iodinated tyrosines from Tg in l
ysosomes, forming T4 and T3 (in T3, one iodine atom is absent compared to T4), a
nd releasing them into the blood. Deiodinase enzymes convert T4 to T3.[17] Thyro
id hormones that are secreted from the gland is about 80-90% T4 and about 10-20%
T3.[13][14]
Cells of the brain are a major target for the thyroid hormones T3 and T4. Thyroi
d hormones play a particularly crucial role in brain maturation during fetal dev
elopment.[18] A transport protein that seems to be important for T4 transport ac
ross the blood-brain barrier (OATP1C1) has been identified.[19] A second transpo
rt protein (MCT8) is important for T3 transport across brain cell membranes.[19]
Non-genomic actions of T4 are those that are not initiated by liganding of the h
ormone to intranuclear thyroid receptor. These may begin at the plasma membrane
or within cytoplasm. Plasma membrane-initiated actions begin at a receptor on th
e integrin alphaV beta3 that activates ERK1/2. This binding culminates in local
membrane actions on ion transport systems such as the Na(+)/H(+) exchanger or co
mplex cellular events including cell proliferation. These integrins are concentr
ated on cells of the vasculature and on some types of tumor cells, which in part
explains the proangiogenic effects of iodothyronines and proliferative actions
of thyroid hormone on some cancers including gliomas. T4 also acts on the mitoch
ondrial genome via imported isoforms of nuclear thyroid receptors to affect seve
ral mitochondrial transcription factors. Regulation of actin polymerization by T
4 is critical to cell migration in neurons and glial cells and is important to b
rain development.
T3 can activate phosphatidylinositol 3-kinase by a mechanism that may be cytopla
smic in origin or may begin at integrin alpha V beta3.
In the blood, T4 and T3 are partially bound to thyroxine-binding globulin (TBG),
transthyretin, and albumin. Only a very small fraction of the circulating hormo
ne 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 cros
s the cell membrane and bind to intracellular receptors (a1, a2, ß1 and ß2), which a
ct alone, in pairs or together with the retinoid X-receptor as transcription fac
tors to modulate DNA transcription[1].
[edit] T3 and T4 regulation
The production of thyroxine and triiodothyronine is regulated by thyroid-stimula
ting hormone (TSH), released by the anterior pituitary. The thyroid and thyrotro
pes form a negative feedback loop: TSH production is suppressed when the T4 leve
ls are high. The TSH production itself is modulated by thyrotropin-releasing hor
mone (TRH), which is produced by the hypothalamus and secreted at an increased r
ate in situations such as cold (in which an accelerated metabolism would generat
e more heat). TSH production is blunted by somatostatin (SRIH), rising levels of
glucocorticoids and sex hormones (estrogen and testosterone), and excessively h
igh blood iodide concentration.
An additional hormone produced by the thyroid contributes to the regulation of b
lood calcium levels. Parafollicular cells produce calcitonin in response to hype
rcalcemia. Calcitonin stimulates movement of calcium into bone, in opposition to
the effects of parathyroid hormone (PTH). However, calcitonin seems far less es
sential than PTH, as calcium metabolism remains clinically normal after removal
of the thyroid (thyroidectomy), but not the parathyroids.
[edit] Thyroid function laboratory tests - normal ranges[20]
Test Abbreviation Normal ranges
Serum thyrotropin/thyroid-stimulating hormone TSH 0.3 3.0 µU/ml
Free thyroxine FT4 7 18 ng/l = 0.7 1.8 ng/dl
Serum triiodothyronine T3 800 ng/l 1.8 µg/l = 80 180 ng/dl
Radioactive iodine-123 uptake RAIU 10 30%
Radioiodine scan (gamma camera) N/A N/A - thyroid contrasted images
Free thyroxine fraction FT4F 0.03 0.005%
Serum thyroxine T4 46 120 µg/l = 4.6 12.0 µg/dl
Thyroid hormone binding ratio THBR 0.9 1.1
Free thyroxine index FT4I 4 11
Free triiodothyronine l FT3 230 619 pg/d
Free T3 Index FT3I 80 180
Thyroxine-binding globulin TBG 12 20 ug/dl T4 +1.8 µg
TRH stimulation test Peak TSH 9 30 µIU/ml at 20 30 min.
Serum thyroglobulin l Tg 0-30 ng/m
Thyroid microsomal antibody titer TMAb Varies with method
Thyroglobulin antibody titer TgAb Varies with method
µU/ml = mU/l, microunit per milliliter
ng/dl, nanograms per deciliter
µg, micrograms
pg/d, picograms per day
µIU/ml = mIU/l, micro-international unit per milliliter
See [2] for more information on medical units of measure
[edit] Significance of iodine
In areas of the world where iodine is lacking in the diet the thyroid gland can
become considerably enlarged, a condition called 'endemic goitre'. Pregnant wome
n on a diet that is severely deficient of iodine can give birth to infants who c
an present with thyroid hormone deficiency, manifesting in problems of physical
growth and development as well as brain development (a condition referred to as
'endemic cretinism'), and is one cause of congenital hypothyroidism. In many dev
eloped countries, newborns are routinely tested for congenital hypothyroidism as
part of newborn screening. Children with congenital hypothyroidism are treated
supplementally with levothyroxine, which facilitates normal growth and developme
nt.
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 in
to frogs; in contrast, administering thyroxine will trigger metamorphosis.
Because the thyroid concentrates this element, it also concentrates various radi
oactive isotopes of iodine produced by nuclear fission. In the event of large ac
cidental releases of such material into the environment, the uptake of radioacti
ve iodine isotopes by the thyroid can, in theory, be blocked by saturating the u
ptake mechanism with a large surplus of non-radioactive iodine, taken in the for
m of potassium iodide tablets. One consequence of the Chernobyl disaster was an
increase in thyroid cancers in children in the years following the accident.[21]
The use of iodised salt is an efficient way to add iodine to the diet. It has el
iminated endemic cretinism in most developed countries, and some governments hav
e made the iodination of flour, cooking oil, and salt mandatory. Potassium iodid
e and sodium iodide are typically used forms of supplemental iodine.
As with most substances, either too much or too little can cause problems. Recen
t studies on some populations are showing that excess iodine intake could cause
an inceased prevelence of autoimmune thyroid disease, resulting in permanent hyp
othyroidism.[22]
[edit] Treatment for Hyperthyroidism
Beta blockers are used to decrease symptoms like fast heart rate, tremors, anxie
ty and chest palpitations, and are sometimes anti thyroid drugs used to block th
yroid hormones, in particular, in the case of Graves' disease. These medications
take several months to take full effect and have side-effects like skin rash or
a drop in white blood cell count, which decreases the ability of the body to fi
ght off infections. Sometimes these drugs involve frequent dosing (such as one p
ill each 8 hours) and require frequent doctor visits (blood tests) to track impa
cts and progress, and sometimes may be ineffective at free. Because of the side-
effects and treatment protocol of drugs, many patients choose to undergo surgery
or more commonly the use of radioactive iodine 131, a type of radioiodine. Some
times, radioiodine is administered under a thyroid ablation procedure to severel
y restrict or altogether destroy the gland; the radioactive iodine is selectivel
y taken up by the gland and gradually thins out producing cells and destroys the
tissues. The treatment has been noted to be safe and effective.
Individuals that have underactivity of the thyroid gland require hormone replace
ment therapy. Several types of thyroid hormone replacements are available and al
l are very safe but need to be taken for the rest of one's life. Thyroid hormone
treatment is given under the care of a physician and may take a few weeks to be
come effective.[23]
Surgery is sometimes used to treat overactive thyroid, thyroid nodules, and ofte
n for thyroid cancers. The surgery is quite effective but can have a few side-ef
fects or risks:
The nerves controlling the vocal cords can be damaged.
The parathyroid glands that produce parathyroid hormone (PTH) can be destroyed a
nd one can develop bleeding.
If the entire thyroid gland is removed, one develops hypothyroidism, which entai
ls taking hormone supplements for the rest of one's life.[24]
[edit] History
There are several findings that evidence a great interest for thyroid disorders
just in the Medieval Medical School of Salerno (12th century). Rogerius Salernit
anus, the Salernitan surgeon and author of "Post mundi fabricam" (around 1180) w
as considered at that time the surgical text par excellence all over Europe. In
the chapter "De bocio" of his magnum opus, he describes several pharmacological
and surgical cures, some of which nowadays are reappraised quite scientifically
effective.[25]
In modern times, the thyroid was first identified by the anatomist Thomas Wharto
n (whose name is also eponymised in Wharton's duct of the submandibular gland) i
n 1656.[26]
Thyroxin was identified only in the 19th century.
[edit] In other animals
The thyroid gland is found in all vertebrates. In fish, it is, in general, locat
ed below the gills and is not always divided into distinct lobes. However, in so
me teleosts, patches of thyroid tissue are found elsewhere in the body, associat
ed with the kidneys, spleen, heart, or eyes.[27]
In tetrapods, the thyroid is always found somewhere in the neck region. In most
tetrapod species, there are two paired thyroid glands - that is, the right and l
eft lobes are not joined together. However, there is only ever a single thyroid
gland in most mammals, and the shape found in humans is common to many other spe
cies.[27]
In larval lampreys, the thyroid originates as an exocrine gland, secreting its h
ormones into the gut, and associated with the larva's filter-feeding apparatus.
In the adult lamprey, the gland separates from the gut, and becomes endocrine, b
ut this path of development may reflect the evolutionary origin of the thyroid.
For instance, the closest living relatives of vertebrates, the tunicates and Amp
hioxus, have a structure very similar to that of larval lampreys, and this also
secretes iodine-containing compounds (albeit not thyroxine).[27]
[edit] Additional images