Download Thyroid Disease

•The foundations of the endocrine
system are the hormones and glands.
• Hormones are chemical messengers
that send information to the various
glands throughout the body.
•A gland is a group of cells that
produces and secretes chemicals.
• The thyroid is an example of an
endocrine gland that controls the
body’s metabolism.
•The thyroid gland is located in the
anterior neck below the skin and muscle
layers. It is the biggest gland found in
the neck
•The thyroid gland takes the shape of a
butterfly. Its two lobes wrap around the
trachea.
•The thyroid controls metabolism through
thyroid hormone.
•Thyroid hormones increases cellular
activity in almost all tissues of the body
•The thyroid gland produces two
important hormones
•tetraiodothyronine
(thyroxine or T4)
•triiodothyronine (T3)
•These hormones are
needed by the body since
they control metabolism,
growth, and development.
•The thyroid gland is influenced by
hormones produced by two other organs
•In the brain, the pituitary gland,
produces thyroid stimulating
hormone (TSH).
•The hypothalamus, located just
above the pituitary, produces
thyrotropin releasing hormone
(TRH).
Hypothyroidism
(Low Thyroid Hormone Levels)
Thyroid Hormone
(T3 & T4)
THR in hypothalamus &
TSH in anterior pituitary
Hyperthyroidism
(High Thyroid Hormone Levels)
Thyroid Hormone
(T3 & T4)
THR in hypothalamus &
TSH in anterior pituitary
•Normally, TSH increases the
uptake of iodine by the thyroid gland
and increases production of thyroid
hormone.
•If there is little iodine available in
one’s diet, insufficient thyroid
hormone is produced by the thyroid.
•As a result, extra TSH is produced.
This enables the thyroid to take in
most of the iodine presented to it
from food and water.
•Yet, the TSH also causes growth of
thyroid cells and the thyroid gland
becomes enlarged, forming this
goiter.
•These are the areas
in the world where
people once suffered
from iodine deficiency
in their diets.
•Some of these areas
still exist, especially in
third world countries.
•As a result, goiters
are prevalent in these
areas.
• Before the
iodinization of salt,
areas of the United
Stated were affected
by iodine deficiency.
•In autoimmune diseases, the patient’s immune
system begins to attack itself, recognizing its own
cells as foreign and attacking them.
•Most autoimmune diseases occur in women, and
usually during their childbearing years.
•Autoimmunity is the cause for most cases of thyroid
disease.
•One example is Graves’ disease (hyperthyroidism)
that occur more often in women at a 7 to 1 ratio.
•Another example is Hastimoto’s thyroiditis
(hypothyroidism) that occurs more often in women at
a 50 to 1 ratio.
•Graves' disease is an autoimmune disease
that causes hyperthyroidism.
•The immune system activation targets the
thyroid gland and causes overproduction of
thyroid hormones.
•As a result of the overactivity of the thyroid
gland, there is an increase in thyroid hormone
in the blood (T3 & T4).
•Graves' disease occurs in less that 1/4 of 1%
of the population.
• Weight loss
•Increased appetite
•Nervousness
•Restlessness
•Heat intolerance
•Increased sweating
•Fatigue
•Muscle weakness
•Protruding eyes (less common in children)
•Double vision
•Eye irritation
•Tremor
•Frequent bowel movements
• Decreased menses
•Goiter (possible)
•Physical examination shows an increased heart
rate along with tremor.
•Examination of the neck may show thyroid
enlargement or goiter.
•TSH
•T3 & T4
•Radioactive iodine uptake
•TSI (Thyroid stimulating immunoglobulin)
•Beta-blockers (Propranolol / Inderal ) are often used to treat
symptoms of rapid heart rate, sweating, and anxiety until the
hyperthyroidism is controlled.
•Anti-thyroid drugs inhibit production or conversion of the
active thyroid hormone
• Examples of these drugs include Propothiuracil (PTU) /
Methimazole (Tapazole)
•Drug treatment about 20-30% effective
•Radioactive iodine (I-131)
•This treatment destroys part or all of the
thyroid gland and renders it incapable of
overproducing thyroid hormone
•Surgery
•During a subtotal thyroidectomy, the
surgeon removes most of the thyroid gland
and renders it incapable of overproducing
thyroid hormone.
•These treatments result in about a 90-95% remission rate of
the disease.
•Yet, radiation and surgery result in the need for lifelong use
of replacement thyroid hormones, because these treatments
destroy or remove the gland.
•Hashimoto's Thyroiditis is an
autoimmune disease which
causes hypothyroidoism.
•The immune system attacks the
thyroid gland causing it to
produce less thyroid hormone.
•As a result of the underactivity of
the thyroid gland, there is an
decrease in thyroid hormone in
the blood (T3 & T4).
•Weight gain
•Goiter
•Intolerance to cold
•Fatigue
•Constipation
•Dry skin
•Hair loss
•Heavy menses
•Difficulty concentrating
•Joint stiffness
•Facial swelling
•Physical examination shows and decreased
heart rate along with extreme fatigue.
•Examination of the neck may show thyroid
enlargement or goiter.
•TSH
•T3 & T4
•Antithyroid peroxidase antibody
•Antithyroglobulin antibody
•The only treatment for hypothyroidism is to
make up for the thyroid hormone the body is
lacking.
•Replacement therapy with thyroid hormone is
taken orally.
•The drug used to treat this condiditon is
Levothyroxine or Synthroid.
•Replacement hormone needs to be taken for
life when the thyroid fails to produce the
necessary hormones for proper metabolic
activity.
•Thyroid hormone actions are
mediated by nuclear receptors that
bind triiodothyronine (T3) with high
affinity, and its precursor thyroxine
(T4) with lower affinity.
•The molecule shown below
represents the human thyroid
hormone receptor beta-1 binding
with a T3 thyroid hormone
molecule. I used the Protein Data
Bank entry 1-XZX entitled
Thyroxine-Thyroid Hormone
Receptor Interactions.
•tThe thyroid hormone receptor is
colored cyan. The molecule T3 is
shown in magenta.
•The main difference between the
two thyroid hormones is that T4
contains a bulky 5' iodine group
absent from T3.
•The magenta T3 molecule is shown
here highlights the fact that it only
contains three iodine molecules in
contrast to thyroxine, which has four
iodine molecules.
•The iodine molecules are shown in
red.
•The thyroid hormone receptor
molecule represented as the cyan
ribbon is the ligand in which T3
binds to in order function in the
body.
•The molecule shown contains a
ligand binding pocket that
accommodates T3.
•The thyroid hormone receptor
would need to undergo structural
alterations in order to permit T4 into
this binding site since T4 contains
an extra bulky 5 prime iodine group
not present in T3.
•The thyroid hormone T3
must interact with residues
on the hormone receptor
before the it can bind to
onto its binding site.
•The T3 interacts with
Histidine (His 435),
Methionine (Met 313 and
Met 310), Isoleucine (Ile
276), and Phenylalanine
(Phe 459, and Phe 455)
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Images
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