The Thyroid Gland and its

Hormones
 Physiology and Anatomy of The Thyroid Gland
The gland contains many follicles.
• A follicle is a fluid-filled lumen. The lumen contains material called colloid. The
major constituent of colloid is the large glycoprotein thyroglobulin, which
contains the thyroid hormones. Each follicle is lined by cuboidal epithelial cells,
also called the follicular cells.
• There are also extrafollicular hormone-secreting cells, called C cells.
 Hormones Produced in the thyroid
 Triiodothyronine (T3): made in follicle
 Thyroxine (T4): made in follicle
 Calcitonin: made by C cells
• Triiodothyronine and Thyroxine profoundly increase the metabolic
rate of the body.
• Complete lack of thyroid secretion usually causes the basal metabolic
rate to fall 40% to 50% below normal, and extreme excesses of
thyroid secretion can increase the basal metabolic rate to 60% to
100% above normal.
• The functions of these two hormones are qualitatively the same, but
they differ in rapidity and intensity of action.

Follicular cells require about 50 milligrams Iodine a year, or 1mg / week to

form normal quantities of thyroxine.
 Synthesis of Thyroid Hormones

1. Thyroglobulin Synthesis
• Endoplasmic reticulum and Golgi apparatus in the follicular cells of
thyroid gland synthesize and secrete thyroglobulin.
• Thyroglobulin molecule is a large glycoprotein containing molecules of
amino acid tyrosine. After synthesis, thyroglobulin is stored in the
follicle.

2. Iodide Trapping
• Iodide is actively transported from blood into follicular cell, by sodium-
iodide symporter pump.
• This process of concentrating the iodide in the cell is called iodide
trapping.
• In a normal gland, the iodide pump concentrates the iodide to about 30
times its concentration in the blood.
3. Transport of Iodide into Follicular Cavity

• From the follicular cells, iodide is transported into the follicular cavity
through the apical membrane by a chloride-iodide ion counter-
transporter molecule called pendrin.
4. Oxidation of Iodide
• Iodide must be oxidized to elementary iodine (I).
• The oxidation of iodide into iodine occurs inside the follicular cells in
the presence of thyroid peroxidase and its accompanying hydrogen
peroxide, which is located in the apical membrane of the cell.
• This providing the oxidized iodine at exactly the point in the cell where
the thyroglobulin molecule enters the colloid.
 5. Iodination of Tyrosine and Coupling Reactions
• In the follicular lumen, iodine binds with thyroglobulin.
• Combination of iodine with tyrosine is known as iodination. It takes
place in thyroglobulin.
• Iodine (I) combines with tyrosine, which is already present in
thyroglobulin, with the enzyme peroxidase.
• Iodination of tyrosine occurs in several stages.
• Tyrosine is iodized first into monoiodotyrosine (MIT) and later into
diiodotyrosine (DIT).
• MIT and DIT get coupled with one another.
• The coupling occurs in different configurations, to give rise to different
thyroid hormones.
Tyrosine + I = Monoiodotyrosine (MIT)
MIT + I = Di-iodotyrosine (DIT)
DIT + MIT = Tri-iodothyronine (T3)
MIT + DIT = Reverse T3
DIT + DIT = Tetraiodothyronine or Thyroxine (T4)
 Thyroid Hormone Synthesis & Secretion

Each thyroglobulin molecule contains 140 molecules of tyrosine. T3 and T4 are

breakdown products of thyroglobulin
Release of Thyroid Hormones and Transport to tissues
Before being released into the blood, the hormones are first cleaved from
thyroglobulin. Then they are released into the blood.
1. Follicular cell sends foot-like extensions called pseudopods, which
close around the thyroglobulin-hormone complex.
2. Pseudopods convert thyroglobulin-hormone complex into small
pinocytic vesicles.
3. Digestive enzymes such as proteinases digest (proteolysis) the
thyroglobulin and release the hormones.
4. The hormones diffuse through base of the follicular cell and enter the
capillaries.
5. MIT and DIT are not released into blood. These residues are
deiodinated by an enzyme called iodotyrosine deiodinase, resulting in
the release of iodine.
6. Only T3 and T4 are released into the blood.
7. Upon entering the blood, the thyroxine and triiodothyronine combines
immediately with several of the plasma proteins.
8. Then the thyroid hormones are released to the tissue cells slowly.
 Regulation of Thyroid Hormone Secretion
• To achieve the ideal level of Thyroid hormone secretion, specific
feedback mechanisms operate through the hypothalamus and
anterior pituitary gland to control the rate of thyroid secretion.
• Thyroid-Stimulating Hormone (TSH), also known as thyrotropin,
is an anterior pituitary hormone. It increases secretion of thyroxine
and triiodothyronine.
• Secretion of TSH from the Anterior pituitary is controlled by a
hypothalamic hormone, thyrotropin-releasing hormone (TRH).
TRH is transported to the anterior pituitary by way of the
hypothalamic-hypophysial portal blood, where it stimulates the
anterior pituitary to release TSH.
• TRH secretion by anterior pituitary is inhibited in a negative
feedback fashion by circulating T4 and T3. Although some
feedback occurs at the hypothalamus by influencing TRH secretion,
the predominant feedback occurs at the level of the pituitary.
 Regulation of Thyroid Hormone Secretion

Figure 77-7: Regulation of thyroid secretion. T3, triiodothyronine; T4, thyroxine.

 Thyroid hormone activation of target cells
• Thyroxine (T4) and triiodothyronine (T3) readily diffuse through
the cell membrane.
• Much of the T4 is deiodinated to form T3 as thyroid hormone
receptors have a high affinity for T3.
• T3 interacts with the thyroid hormone receptor, bound as a
heterodimer with a retinoid X receptor, on the thyroid hormone
response element of the target genes.
• This causes either increases or decreases in transcription of target
genes that lead to formation of new proteins.
• Therefore, great numbers of protein enzymes, structural proteins,
transport proteins, and other substances are synthesized in the
almost all the cells.
• Most of the actions of thyroid hormone result from the
subsequent enzymatic and other functions of these new proteins
to cause a generalized increase in functional activity throughout
the body.
Figure 77-5:Thyroid hormone activation of target
 Physiological effect of thyroid hormones:

1. THYROID HORMONES INCREASE CELLULAR

METABOLIC ACTIVITY
• Thyroid hormones increase the metabolic activities of almost all the
tissues of the body.
• The rate of utilization of foods for energy is greatly accelerated.
• Although the rate of protein synthesis is increased, at the same time
the rate of protein catabolism is also increased.
• Increased Number and activity of Mitochondria  increased ATP to
energize cellular function.
• Increased Active Transport of Ions Through Cell Membranes.
 2. EFFECT OF THYROID HORMONE ON GROWTH

• In humans, the effect of thyroid hormone on growth is manifest

mainly in growing children.
• In children with hypothyroidism, the rate of growth is greatly
retarded.
• In children with hyperthyroidism, excessive skeletal growth often
occurs, causing the child to become considerably taller at an earlier
age, however, the duration and eventual height of the adult may
actually be shortened due to early closure of epiphysis with bone
shaft.
• Thyroid hormone also promotes growth and development of the
brain during fetal life and for the first few years of postnatal life.
3. EFFECTS OF THYROID HORMONE ON SPECIFIC
BODY FUNCTIONS
1. Stimulation of Carbohydrate Metabolism: Thyroid hormone
stimulates almost all aspects of carbohydrate metabolism.

2. Stimulation of Fat Metabolism: Essentially all aspects of fat

metabolism are also enhanced by thyroid hormone. Lipids are
mobilized rapidly from the fat tissue, which decreases fat stores of
the body and increases free fatty acid concentration in the plasma.

3. Effect on Plasma and Liver Fats: Increased thyroid hormone

decreases the concentrations of cholesterol, phospholipids, and
triglycerides in the plasma, whereas decreased thyroid hormone
has the reverse effect.
3. EFFECTS OF THYROID HORMONE ON SPECIFIC
BODY FUNCTIONS
4. Increased Requirement for Vitamins: vitamins are essential
parts of some of the enzymes or coenzymes, so as thyroid
hormones cause an increase in many enzymes, there is an
increased need for vitamins.

5. Cardiovascular effects: Increased blood flow to the tissues and

increased cardiac output, increased HR.

6. Increased Gastrointestinal Motility: Thyroid hormone increases

appetite, food intake, secretion of digestive juices and motility of
the gastrointestinal tract. Hyperthyroidism often results in
diarrhea, whereas lack of thyroid hormone can cause constipation.
3. EFFECTS OF THYROID HORMONE ON SPECIFIC
BODY FUNCTIONS
7. Excitatory Effects on the Central Nervous System: In general,
thyroid hormone increases the rapidity of cerebration (thinking),
although thought processes may be dissociated. Conversely, lack
of thyroid hormone decreases rapidity of cerebration. A person
with hyperthyroidism is likely to be extremely nervous and have
many psychoneurotic tendencies, such as anxiety complexes,
extreme worry, and paranoia.

8. Decreased Body Weight: A greatly increased amount of thyroid

hormone almost always decreases body weight, and a greatly
decreased amount of thyroid hormone almost always increases
body weight.
3. EFFECTS OF THYROID HORMONE ON SPECIFIC
BODY FUNCTIONS
9. Effect on the Muscles. A slight increase in thyroid hormone
usually makes the muscles react with vigor but, with excessive
thyroid hormone, the muscles become weakened because of
excess protein catabolism. Conversely, lack of thyroid hormone
causes the muscles to become sluggish, and they relax slowly after
a contraction.
10. Muscle Tremor. One of the most characteristic signs of
hyperthyroidism is a fine muscle tremor.

11. Effect on Other Endocrine Glands. It caused increased secretion

of other endocrine glands.

12. Effect of Thyroid Hormone on Sexual Function. For normal

sexual function, thyroid secretion needs to be approximately
normal.
 3. EFFECTS OF THYROID HORMONE ON SPECIFIC
BODY FUNCTIONS

13. Effect on Sleep. Because of the exhausting effect of thyroid

hormone on the musculature and on the central nervous system,
persons with hyperthyroidism often have a feeling of constant
tiredness, but because of the excitable effects of thyroid hormone on
the synapses, it is difficult to sleep. Conversely, extreme somnolence
is characteristic of hypothyroidism, with sleep sometimes lasting
12 to 14 hours a day.
 Diseases of the Thyroid

1. Hyperthyroidism

2. Hypothyroidism
 Diseases of the Thyroid

1. Hyperthyroidism:
It is the condition that occurs due to excessive production of thyroid
hormones by the thyroid gland.

The thyroid gland is increased to two to three times its normal size,
with tremendous increase in the number of follicular cells.

Hyperthyroidism is caused by:

A. Graves’ disease
B. Thyroid adenoma
Hyperthyroidism causes:

A. Graves’ disease is an autoimmune disease.

• Normally, TSH (Thyroid Stimulating Hormone) combines with
receptors of thyroid cells and causes the synthesis and secretion of
thyroid hormones.
• In Graves’ disease, the body produces autoimmune antibodies
called thyroid-stimulating immunoglobulins (TSIs). These
antibodies act like TSH by binding with receptors of TSH of the
thyroid follicular cells. This results in hypersecretion of thyroid
hormones.
• The high concentration of thyroid hormones caused by the
antibodies also suppresses the anterior pituitary TSH production.

B. Thyroid adenoma is a localized tumor in the thyroid tissue.

• It secretes large quantities of thyroid hormones.
• Here also, the TSH production from anterior pituitary is depressed.
Symptoms of Hyperthyroidism
(1) A high state of excitability
(2) Intolerance to heat
(3) Increased sweating
(4) Mild to extreme weight loss
(5) Varying degrees of diarrhea
(6) Muscle weakness
(7) Nervousness or other psychic disorders
(8) Extreme fatigue but inability to sleep
(9) Tremor of the hands
(10)Exophthalmos (protrusion of the eyeballs)

Management of Hyperthyroidism:

• Antithyroid drug (decreases thyroid hormone levels)

• Thyroidectomy
• Radioactive iodine ( I-131)
2. Hypothyroidism
Causes of Hypothyroidism:

A. Hashimoto’s disease
B. Goiter

C. Hashimoto’s disease:
• It is an autoimmune disease against the thyroid gland, but in this
case the autoimmunity destroys the gland.
B. Goiter
Goiter means a greatly enlarged thyroid gland. When adequate amounts
of iodine are not obtained people develop extremely large thyroid
glands, called endemic colloid goiters.
Mechanism:
• Lack of iodine prevents production of bothT3 and T4
• So no hormone is available to inhibit production of TSH by the
anterior pituitary gland so pituitary secretes excessively large
quantities of TSH
• TSH stimulates the thyroid to secrete large amounts of thyroglobulin
colloid into the follicles, and the gland grows larger and larger
• However, because of lack of iodine, production of T3 and T4 does not
occur and therefore does not cause the normal suppression of TSH
production by the anterior pituitary.
• The follicles greatly enlarge, and the thyroid gland may increase to
10 to 20 times its normal size.
A goiter patient
Physiological Characteristics of
Hypothyroidism.
• fatigue and extreme somnolence
• extreme muscular sluggishness
• a slowed heart rate and decreased
cardiac output
• sometimes increased body weight
• constipation
• mental sluggishness
• development of an edematous
appearance throughout the body called
myxedema.
• Atherosclerosis
 Cretinism
• It is caused by severe hypothyroidism in utero, infancy or
childhood.
• It is characterized by failure of body growth and by mental
retardation.
• It results from congenital lack of a thyroid gland, from failure of
the thyroid gland to produce thyroid hormone because of a genetic
defect of the gland, or from a lack of iodine in the diet (endemic
cretinism).
• Skeletal growth is more affected than the soft tissues.
• As a result the soft tissues are likely to enlarge excessively, giving
the child an obese, stocky, and short appearance.
• Occasionally the tongue becomes so large in relation to the skeletal
growth that it obstructs swallowing and breathing, inducing a
characteristic guttural breathing that sometimes chokes the child.
Cretinism
What is a blood test for thyroid hormones?
• The thyroid gland continually releases a certain amount of
hormones into the blood. So a blood test can be used to
determine the amounts of hormones produced by the thyroid
gland.
• The blood test measures TSH and the thyroid hormones
triiodothyronine (T3) and thyroxine (T4).
• A change in the TSH level can be an early detector for a thyroid
function problem. This is why often, as a first step, only TSH is
measured.
• If the TSH level in the blood is higher or lower than normal, the
thyroid hormones T4 and T3 are also measured.
• Because most thyroid hormones are bound to certain blood
proteins and only free hormones (which are not bound to
proteins) act in the body, nowadays only the so-called “free
thyroid hormones” (FT3 and FT4 – with “F” standing for “free”)
are measured.
• Thyroid antibodies are measured when looking for the cause of a
thyroid function problem. Apparently, if our immune system
wrongly regards the body’s own thyroid gland cells as foreign
substances, it produces thyroid antibodies.
 Treatment

• A drug that is similar to the body’s own hormones can be used to

replace thyroxine when levels are too low. This drug is usually
referred to as Levothyroxine or L-thyroxine. It keeps hormone
levels within the normal range, and symptoms usually clear up
completely. Depending on the cause, treatment may be temporary
or lifelong.
• Thyroxine is taken as a tablet once a day. At the right dose side
effects are virtually nonexistent. The dose is based mostly on body
weight.