Thyroid
From Wikipedia, the free encyclopedia
The thyroid gland controls how quickly the body uses energy, makes
proteins, and controls how sensitive the body is to other
hormones. It participates in these processes by producing thyroid hormones, the principal ones being
triiodothyronine (T
3) and
thyroxine which can sometimes be referred to as tetraiodothyronine (T
4). These hormones regulate the
rate of metabolism and affect the growth and rate of function of many other systems in the body. T
3 and T
4 are synthesized from both
iodine and
tyrosine. The thyroid also produces
calcitonin, which plays a role in
calcium homeostasis.
The thyroid gets its name from the Greek word for "shield", due to
the shape of the related thyroid cartilage. The most common problems of
the thyroid gland consist of an overactive thyroid gland, referred to as
hyperthyroidism, and an underactive thyroid gland, referred to as
hypothyroidism.
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 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 cartilage (just below the laryngeal prominence, or '
Adam's Apple'), and extends inferiorly to approximately the fifth or sixth
tracheal ring.
[1]
It is difficult to demarcate the gland's upper and lower border with
vertebral levels because it moves position in relation to these during
swallowing.
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, can change
shape 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.
Evolution
Phylogenetically, thyroid cells are derived from primitive
iodide-concentrating gastroenteric cells. Given the essential nature of
iodine compounds in living organisms, organisms moving from iodine-rich
seas to iodine-deficient land needed stronger systems for uptake and
storage of that element. The thyroid appears to have evolved to serve
that need. Venturi et al.
[5] suggested that
iodide
has an ancestral antioxidant function in all iodide-concentrating cells
from primitive algae to more recent vertebrates. In 2008, this
ancestral antioxidant action of iodides has been experimentally
confirmed by Küpper et al.
[6]
Thyroxine has a 700 million year history. It is present, while showing
no hormonal action, in the fibrous exoskeletal scleroproteins of the
lowest invertebrates,
Porifera and
Anthozoa. The active hormone, triiodothyronine (T
3), became active in metamorphosis and
thermogenesis,
allowing for better adaptation of organisms to terrestrial environment
(fresh water, atmosphere, gravity, temperature and diet).
Embryological development
Floor of pharynx of embryo between 18 and 21 days.
In the fetus
[clarification needed],
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 later indicated by the
foramen cecum. The thyroid then 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, passing
anterior to the hyoid bone. During migration, the thyroid remains
connected to the tongue by a narrow canal, the thyroglossal duct.
The portion of the thyroid containing the parafollicular C cells,
those responsible for the production of calcitonin, are derived from the
neural crest. This is first seen as the
ultimobranchial body, which joins the primordial thyroid gland during its descent to its final location in the anterior neck.
Histology
At the microscopic level, there are three primary features of the thyroid:
[10]
Histological section through the thyroid of a horse. 1 follicles, 2 follicular epithelial cells, 3 endothelial cells
| 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, but also for storage of iodine in thyroglobulin,
in fact iodine is necessary for other important iodine-concentrating
organs as breast, stomach, salivary glands, thymus etc. (see iodine in biology).
Twenty-five percent of all the body's iodide ions are in the thyroid
gland. Inside the follicles, colloid serves as a reservoir of materials
for thyroid hormone production and, to a lesser extent, acts as a
reservoir for the hormones themselves. Colloid is rich in a protein
called thyroglobulin.
|
Thyroid epithelial cells
(or "follicular cells") |
The follicles are surrounded by a single layer of thyroid 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. When active, the epithelial cells become tall columnar cells. |
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
T3 and T4 production and action
Thyroxine (T
4) 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)
[16]
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 cleave the iodinated tyrosines from Tg in lysosomes, forming T
4 and T
3 (in T
3, one iodine atom is absent compared to T
4), and releasing them into the blood.
Deiodinase enzymes convert T
4 to T
3.
[17] Thyroid hormone secreted from the gland is about 80-90% T
4 and about 10-20% T
3.
[11][12]
Cells of the developing brain are a major target for the thyroid hormones T
3 and T
4. Thyroid hormones play a particularly crucial role in brain maturation during fetal development.
[18] A transport protein that seems to be important for T
4 transport across the
blood–brain barrier (
OATP1C1) has been identified.
[19] A second transport protein (
MCT8) is important for T
3 transport across brain cell membranes.
[19]
Non-genomic actions of T4 are those that are not initiated
by liganding of the hormone to intranuclear thyroid receptor. These may
begin at the plasma membrane or within cytoplasm. Plasma
membrane-initiated actions begin at a receptor on the 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
complex cellular events including cell proliferation. These integrins
are concentrated 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 mitochondrial
genome via imported isoforms of nuclear thyroid receptors to affect
several mitochondrial transcription factors. Regulation of actin
polymerization by T4 is critical to cell migration in neurons and glial cells and is important to brain development.
T3 and T4 regulation
Disorders
Hyperthyroidism
Hyperthyroidism, or overactive thyroid, is the overproduction of the thyroid hormones T
3 and T
4, and is most commonly caused by the development of
Graves' disease,
[citation needed]
an autoimmune disease in which antibodies are produced which stimulate
the thyroid to secrete excessive quantities of thyroid hormones. The
disease can result in the formation of a toxic
goiter as a result of thyroid growth in response to a lack of
negative feedback mechanisms. It presents with symptoms such as a thyroid goiter, protruding eyes (
exopthalmos),
palpitations, excess
sweating,
diarrhea,
weight loss,
muscle weakness and unusual sensitivity to heat. The
appetite is often increased.
Beta blockers are used to decrease symptoms of hyperthyroidism such as
increased heart rate,
tremors, anxiety and
heart palpitations, and
anti-thyroid drugs are used to decrease the production of
thyroid hormones, in particular, in the case of
Graves' disease. These medications take several months to take full effect and have
side-effects such as skin
rash or a drop in
white blood cell count, which decreases the ability of the body to fight off
infections.
These drugs involve frequent dosing (often one pill every 8 hours) and
often require frequent doctor visits and blood tests to monitor the
treatment, and may sometimes lose effectiveness over time. Due to the
side-effects
[clarification needed] and inconvenience of such drug regimens, some patients choose to undergo radioactive
iodine-131
treatment. Radioactive iodine is administered in order to destroy a
proportion of or the entire thyroid gland, since the radioactive iodine
is selectively taken up by the gland and gradually destroys the cells of
the gland. Alternatively, the gland may be partially or entirely
removed surgically, though iodine treatment is usually preferred since the surgery is
invasive and carries a risk of damage to the
parathyroid glands or the nerves controlling the
vocal cords. If the entire thyroid gland is removed, hypothyroidism results.
[21]
Hypothyroidism
Main article:
Hypothyroidism
Hypothyroidism is the underproduction of the thyroid hormones T
3 and T
4. Hypothyroid disorders may occur as a result of congenital thyroid abnormalities (see
congenital hypothyroidism), autoimmune disorders such as
Hashimoto's thyroiditis,
iodine deficiency
(more likely in poorer countries) or the removal of the thyroid
following surgery to treat severe hyperthyroidism and/or thyroid
cancer. Typical symptoms are abnormal weight gain, tiredness, baldness, cold intolerance, and
bradycardia. Hypothyroidism is treated with
hormone replacement therapy, such as
levothyroxine, which is typically required for the rest of the patient's life. Thyroid hormone treatment is given under the care of a
physician and may take a few weeks to become effective.
[22]
Negative feedback
mechanisms result in growth of the thyroid gland when thyroid hormones
are being produced in sufficiently low quantities as a means of
increasing the thyroid output; however, where the hypothyroidism is
caused by iodine insufficiency, the thyroid is unable to produce T
3 and T
4 and as a result, the thyroid may continue to grow to form a non-toxic
goiter. It is termed non-toxic as it does not produce toxic quantities of thyroid hormones, despite its size.
Initial hyperthyroidism followed by hypothyroidism
This is the overproduction of T3 and T4 followed by the underproduction of T3 and T4. There are two types: Hashimoto's thyroiditis and postpartum thyroiditis.
Hashimoto's thyroiditis or Hashimoto's Disease is an
autoimmune disorder whereby the body's own
immune system reacts with the thyroid
tissues in an attempt to destroy it. At the beginning, the gland may be overactive, and then becomes underactive as the
gland is damaged resulting in too little thyroid hormone production or
hypothyroidism.
Some patients may experience "swings" in hormone levels that can
progress rapidly from hyper-to-hypothyroid (sometimes mistaken as severe
moodswings, or even being
bipolar,
before the proper clinical diagnosis is made). Some patients may
experience these "swings" over a longer period of time, over days or
weeks or even months. Hashimoto's is more common in females than males,
usually appearing after the age of 30, and tends to run in families
meaning it can be seen as a
genetic disease. Also more common in individuals with Hashimoto's Thyroiditis are
type 1 diabetes and
celiac disease.
[23]
Postpartum thyroiditis
occurs in some females following the birth of a child. After delivery,
the gland becomes inflamed and the condition initially presents with
overactivity of the gland followed by underactivity. In some cases, the
gland may recover with time and resume its functions. In others it may
not. The
etiology is not always known, but can sometimes be attributed to autoimmunity, such as
Hashimoto's Thyroiditis or
Graves' Disease.
Cancers
Main article:
Thyroid cancer
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.
[24]
Non-cancerous nodules
Many individuals may find the presence of
thyroid nodules in the neck. The majority of these thyroid nodules are
benign
(non cancerous). The presence of a thyroid nodule does not mean that
one has thyroid disease. Most thyroid nodules do not cause any symptoms,
and most are discovered on an incidental examination. Doctors usually
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.
Congenital anomalies
A
persistent thyroglossal duct
or cyst is the most common clinically significant congenital anomaly of
the thyroid gland. A persistent sinus tract may remain as a vestigial
remnant of the tubular development of the thyroid gland. Parts of this
tube may be obliterated, leaving small segments to form
cysts.
These occur at any age and might not become evident until adult life.
Mucinous, clear secretions may collect within these cysts to form either
spherical masses or fusiform swellings, rarely larger than 2 to 3 cm in
diameter. These are present in the midline of the
neck anterior to the
trachea. Segments of the duct and cysts that occur high in the neck are lined by
stratified squamous epithelium, which is essentially identical to that covering the posterior portion of the
tongue
in the region of the foreamen cecum. The anomalies that occur in the
lower neck more proximal to the thyroid gland are lined by epithelium
resembling the thyroidal acinar epithelium. Characteristically, next to
the lining epithelium, there is an intense lymphocytic inflitrate.
Superimposed infection may convert these lesions into abscess cavities,
and rarely, give rise to cancers.
[citation needed]
Other disorders
- Limited research shows that seasonal allergies may trigger episodes of hypo- or hyperthyroidism.[25][26]
- A ectopic thyroid is an entire or parts of the thyroid located in another part of the body than what is the usual case.
Thyroid function tests
| Test |
Abbreviation |
Normal ranges[27] |
| 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 |
0.8–1.8 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
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
goiter.
Pregnant women on a diet that is severely deficient of iodine can give
birth to infants who can present with thyroid hormone deficiency (
congenital hypothyroidism), manifesting in problems of physical growth and development as well as brain development (a condition referred to as endemic
cretinism). In many developed 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 development.
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; in contrast, administering thyroxine will trigger metamorphosis.
Because the thyroid concentrates this element, it also concentrates the 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. One consequence of the
Chernobyl disaster was an increase in
thyroid cancers in children in the years following the accident.
[28]
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, cooking oil, and salt mandatory.
Potassium iodide and sodium iodide are typically used forms of
supplemental iodine.
As with most substances, either too much or too little can cause
problems. Recent studies on some populations are showing that excess
iodine intake could cause an increased prevalence of
autoimmune thyroid disease, resulting in permanent hypothyroidism.
[29]
History
There are several findings that evidence a great interest for thyroid disorders just in the Medieval Medical School of
Salerno (12th 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 magnum opus, he describes
several pharmacological and surgical cures, some of which nowadays are
reappraised quite scientifically effective.
[30]
Thyroxine was identified only in the 19th century.
In 1909,
Theodor Kocher from Switzerland won the
Nobel Prize in Medicine "for his work on the physiology, pathology and surgery of the thyroid gland".
[32]
In other animals
The thyroid gland is found in all
vertebrates. In fish, it is usually located below the gills and is not always divided into distinct lobes. However, in some
teleosts, patches of thyroid tissue are found elsewhere in the body, associated with the kidneys, spleen, heart, or eyes.
[33]
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 left 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 species.
[33]
In larval
lampreys, the thyroid originates as an
exocrine
gland, secreting its hormones 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, but this path of
development may reflect the evolutionary origin of the thyroid. For
instance, the closest living relatives of vertebrates, the
tunicates and
Amphioxus,
have a structure very similar to that of larval lampreys, and this also
secretes iodine-containing compounds (albeit not thyroxine).
[33]
Additional images
-
Position of the Thyroid in Males and Females
-
-
Section of the neck at about the level of the sixth cervical vertebra.
-
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.
-
-
-
-
