St.

Lukes College of Medicine

William H. Quasha Memorial
Foundations of Medicine
Study Guide Questions for January 22, 2016.
DISEASES OF THE THYROID GLAND
1. Describe the gross anatomy and histology, location and blood supply of
the thyroid gland.
The thyroid is a highly vascular, brownish-red gland located anteriorly
in the lower neck, extending from the level of the fifth cervical vertebra
down to the first thoracic. The gland varies from an H to a U shape and is
formed by 2 elongated lateral lobes with superior and inferior poles
connected by a median isthmus, with an average height of 12-15 mm,
overlying the second to fourth tracheal rings.
This gland secretes iodine containing hormones called Tri-iodo
thyronine (T3) and thyroxine(T4) of which T3 is more active. It regulates
the basal metabolic rate, and it is regulated by the pituitary hormone
TSH. It also secretes calcitonin - which regulates blood calcium levels.
Secretion of calcitonin causes blood calcium levels to drop, and its
secretion is directly dependent on blood calcium levels.

achieved by two main arteries; the superior and inferior thryoid arteries.
These are paired arteries arising on both the left and right.
The superior thyroid artery is the first branch of the external carotid artery.
After arising, the artery descends toward the thyroid gland. As a
generalisation, it supplies the superior and anterior portions of the gland.
The inferior thyroid artery arises from the thyrocervical trunk (which in turn
is a branch of the subclavian artery). The artery travels superomedially to
reach the inferior pole of the thyroid. It tends to supply the posteroinferior aspect.
In a small proportion of people (around 10%), there is an additional artery
present; the thyroid ima artery. It comes from the brachiocephalic trunk of
the arch of aorta, supplying the anterior surface and isthmus.
Venous drainage is carried out by the superior, middle and inferior thyroid
veins, which form avenous plexus. The superior and middle veins drain into
the internal
jugular veins, whereas the inferior drains into
the brachiocephalic vein

The thyroid gland is innervated by branches derived from the sympathetic

trunk. However, these nerves do not control endocrine secretion
release of hormones is regulated by pituitary gland.

Principal innervation of the thyroid gland derives from the autonomic

nervous system. Parasympathetic fibers come from the vagus nerves, and
sympathetic fibers are distributed from the superior, middle, and inferior
ganglia of the sympathetic trunk. These small nerves enter the gland along
with the blood vessels. Autonomic nervous regulation of the glandular
secretion is not clearly understood, but most of the effect is postulated to be
on blood vessels, hence the perfusion rates of the glands.
Three pairs of veins provide venous drainage for the thyroid gland (see the
image below). The superior thyroid vein ascends along the superior thyroid
artery and becomes a tributary of the internal jugular vein. The middle
thyroid vein follows a direct course laterally to the internal jugular vein. The
inferior thyroid veins follow different paths on each side. The right passes
anterior to the innominate artery to the right brachiocephalic vein or
anterior to the trachea to the left brachiocephalic vein. On the left side,
drainage is to the left brachiocephalic vein. Occasionally, both inferior veins
form a common trunk called the thyroid ima vein, which empties into the left
brachiocephalic vein.
Vascular Supply
The thyroid gland secretes hormones directly into the blood. Therefore it
needs to be highly vascularised. Blood supply to the thyroid gland is

Clinical Relevance: Recurrent Laryngeal Nerve

The are two recurrent laryngeal nerves; one left and one right. They arise
from their respective vagus nerves, and descend into the chest.
In the chest, they hook around the subclavian artery (right RL nerve), or the
arch of aorta (left RL nerve). The nerves then ascend back up the neck,
running between thetrachea and oesophagus. They pass underneath
the thryoid gland to innervate the larynx.
During surgery on the thyroid gland, care must be taken not to ligate or
damage the recurrent laryngeal nerves.
HISTOLOGY
THYROID GLAND
The thyroid gland is composed of many spherical hollow sacs called
thyroid follicles. In this tissue section, each follicle (A) appears as an irregular
circle of cells. The principal cells, which surround the follicle are simple
cuboidal epithelium. These follicles are filled with a colloid (B), which usually
stains pink. The principal cells use the thyroglobulin and iodide stored in the
colloid to produce the primary thyroid hormones - including thyroxine.
Between these follicles are the parafollicular cells (C) which
produce calcitonin.
PARATHYROID GLAND
Because the parathyroids (A) are embedded in the thyroid tissue,
their tissues are often found with the thyroid tissue. The chief cells that
make up this gland are smaller and darker staining than those of the
thyroid. At higher magnifications, we could see that the chief cells

appeared in "ribbons" or "cords." These cells secrete parathyroid hormone

(PTH) Recall that you are only responsible for recognizing this tissue when
it appears with the thyroid gland.
2. Discuss briefly the biochemical steps in thyroid hormone synthesis,
storage, release and thyroid receptor interaction. Describe the different
factors that increase or decrease thyroid hormone secretion.

Release of T4 and T3 from Thyroglobulin

Once endocytosed into the follicular epithelial Cell, the thyroglobulin is
broken down by lysosomes, thus releasing attached T4, T3, MIT, and DIT.
T4 and T3 are then transported out of the follicular epithelial cells and into
the circulation. The iodine atoms of MIT and DIT are salvaged and
transported back into the follicular lumen as I-.

Thyroid Hormones are amine hormones and so their synthesis is based on

the amino acid tyrosine. The primary synthetic organ of Thyroid Hormones is
the thyroid gland which produces about twenty times more T4 compared to
T3. T4 is then converted to either T3 or rT3 by the enzyme 'Iodinase' which is
present throughout the body's tissues.
The thyroid gland is full of thyroid follicles which are the basic units of
thyroid hormone synthesis (For detailed histology see Thyroid Histology). The
thyroid follicles are surrounded by a lining of follicular epithelial cells and
contain an acellular lumen full of proteinacious material termed the Thyroid
Colloid. Synthesis of thyroid hormones is a complex multi-step process which
possesses steps that occur within the follicular epithelial cells and also within
the acellular follicular lumen.
THYROID SYNTHESIS

Iodine Transport
Large amounts of Iodine are required for synthesis of physiological
levels of thyroid hormones. To generate sufficient concentrations of Iodine,
the ionic form of the atom, Iodide (I-) is actively transported from the blood
stream into the follicular lumen by the Follicular Epithelial Cells.
Consequently, Iodide is highly concentrated in the thyroid gland compared to
the rest of the body.

General

The first step in the synthesis of thyroid hormones is the

organification of iodine. Iodide is taken up, converted to iodine,
and then condensed onto tyrosine residues which reside along
the polypeptide backbone of a protein molecule called
thyroglobulin. This reaction results in either a mono-iodinated
tyrosine (MIT) or di-iodinated tyrosine (DIT) being incorporated
into thyroglobulin. This newly formed iodothyroglobulin forms
one of the most important constituents of the colloid material,
present in the follicle of the thyroid unit.

The other synthetic reaction, that is closely linked to

organification, is a coupling reaction, where iodotyrosine
molecules are coupled together. If two di-iodotyrosine molecules
couple together, the result is the formation of thyroxin (T4). If a
di-iodotyrosine and a mono-iodotyrosine are coupled together,
the result is the formation of tri-iodothyronine (T3).

From the perspective of the formation of thyroid hormone, the

major coupling reaction is the di-iodotyrosine coupling to produce
T4. Although T3 is more biologically active than T4, the major
production of T3 actually occurs outside of the thyroid gland. The
majority of T3 is produced by peripheral conversion from T4 in a
deiodination reaction involving a specific enzyme which removes
one iodine from the outer ring of T4.

The T3 and T4 released from the thyroid by proteolysis reach the

bloodstream where they are bound to thyroid hormone binding
proteins. The major thyroid hormone binding protein is thyroxin
binding globulin (TBG) which accounts for about 75% of the bound
hormone.

In order to attain normal levels of thyroid hormone synthesis, an

adequate supply of iodine is essential. The recommended
minimum intake of iodine is 150 micrograms a day. Intake of less
than 50 micrograms a day is associated with goiter. High iodine
levels inhibit iodide oxidation and organification. Additionally,
iodine excess inhibits thyroglobulin proteolysis (this is the
principal mechanism for the antithyroid effect of inorganic iodine
in patients with thyrotoxicosis).

Thyroglobulin Synthesis
Thyroglobulin is a protein that contains large numbers of tyrosine
amino acids that go on to become individual thyroid hormone molecules.
Thyroglobulin is synthesized within the follicular epithelial cell and secreted
into the follicular lumen.

Thyroid Peroxidase
Thyroid Peroxidase is an enzyme present in the acellular colloid of the
follicular lumen and performs several key reactions. Thyroid Peroxidase first
generates I2 by oxidizing I- ions present in the follicular lumen. Thyroid
Peroxidase then "organifies" the generated I2 by covalently linking it with the
tyrosine residues present in Thyroglobulin. This generates either single or
doubly-iodinated species of tyrosine, termed "Monoiodotyrosine (MIT)" and
"Diiodotyrosine (DIT)", respectively
o Peroxidase then combines MIT and DIT residues to generate T4 or
T3 species within the thyroglobulin protein, a process termed "Coupling". T4 is
generated by combining two DIT residues while T3 is generated by combining
one DIT residue with one MIT residue. Importantly, peroxidase is much more
efficient at combining of two DIT residues and thus generation of T 4 occurs
much more readily, explaining why the thyroid gland primarily produces
T4 rather than T3. Notably, some MIT and DIT residues do not get coupled and
so peroxidase-processed thyroglobulin will retain some MIT and DIT residues.

Endocytosis of Peroxidase-processed Thyroglobulin

Peroxidase-processed thyroglobulin is then endocytosed by follicular
epithelial cells on a regulated basis whenever the thyroid gland is stimulated
to release thyroid hormone into the circulation. Importantly, peroxidaseprocessed thyroglobulin within the follicle can act as a reservoir for thyroid
hormones in the absence of stimulation for hormone release. Importantly,
this reservoir of peroxidase-processed thyroglobulin is usually enough for
months of use explaining why defects in thyroid hormone synthesis often
take months to become clinically apparent.

3. Discuss briefly the physiologic effects of thyroid hormone.

Overview
Thyroid hormones serve diverse physiological functions critical for
developmental and maintenance of sufficient metabolism. Many of the
sequelae of thyroid hormone deficiency and excess can be inferred from
these physiological functions.
Metabolism
Thyroid hormones enhance whole-body metabolism by modulating the
levels a number of key metabolic and catabolic enzymes in multiple tissues.
By doing so, thyroid hormones enhance the basal metabolic rate and body
temperature. This is likely the most important function of thyroid hormones
in adults.
Autonomic Nervous System
Thyroid Hormones tend to enhance sympathetic nervous system activity
in a number of organs but especially the heart thus directly increasing heart
rate and cardiac output. These cardiac parameters are also enhanced
indirectly by thyroid hormones given the hormones effects on whole-body
metabolism which result in enhanced oxygen demand.

Normal Linear Growth:

Thyroid Hormones cooperate with growth hormone to coordinate
normal linear growth to adult stature.
CNS
Thyroid Hormones are critical for proper brain development in fetuses
and neonates. In adults thyroid hormones appear to speed up the brain's
activity,
GI System
Thyroid Hormones enhance GI Motility as a result hypothyroidism can
result in constipation while hyperthyroidism yields hyperdefecation (this
means increased frequency of well-formed stools and not watery diarrhea).
4.
Describe the effects, signs and symptoms of thyroid hormone
excess and deficiency. Discuss how it affects the hypothalamic- pituitary
thyroid gland axis.
Please read on Hyperthyroidism and Hypothyroidism.