Thyroid Hormone (Thyroxine)

PRECURSOR OF THYROXINE

(MIT)
TYROSINE

(DIT)
3,5,3-triiodothyronine (T3)
 Thyroxine (T4)
3,5,3,5-tetraiodothyronine
 Model of iodide metabolism in the thyroid follicle

Propylthiouracil PEROXIDASE

DEIODINASE

Na+ / K +ATP ase

T 3 - T4
 BIOLOGICAL EFFECTS
The changes initiated by thyroid
hormones are related to an increase
in oxygen consumption, which in turn
translates into heat production.
The chemical reaction associated
with the calorigenic effects takes
place within the mitochondrion of the
cell
 .. Biological effects

Exerts through penetration of plasma

and nuclear membrane
Binds to nuclear receptor
Activates hormone response element
Triggers protein translation
Causes effect
Increases oxygen consumption
Produces heat
Calorigenic effect within the
mitochondrion
 .. Biological effects

Other effects of TH are part of the

regulation of carbohydrate and lipid
metabolism.
Thyroid hormones facilitate glucose
absorption and its transfer into muscle and
fat cells.
It does this through facilitation of insulin
mediated glucose uptake.
When the circulatory concentration of TH is
low, there is a predominant glycogenesis
and, when the concentration increases it
reverts to predominant glycogenolysis
 .. Biological effects

Regulation of carbohydrate metabolism

Increase absorption of glucose
Enhancement of glucose transfer to
muscle and fat
Facilitation of insulin mediated glucose
uptake
Glycogenesis (low TH)
Glycogenolysis (high TH)
Influence lipid metabolism
Lipolysis
Reduction of cholesterol
 .. Biological effects

TH enhances the effect caused by sympathetic nervous

stimulation, such as that of the -adrenergic receptors.
During early development, it contributes to the normal
development of the CNS to the extent that deficiencies at
this time result in abnormalities such as cretinism.
In adults, a normal circulatory concentration of TH
maintains a basic degree of alertness, which translates in
lethargy under hypothyroid conditions.
Thyroid hormones also support cardiac function by
increasing heart rate and the force of contraction, which
in turn translates to an elevation in blood pressure and an
increase in cardiac output
 Further TH effects
Enhance sympathetic nervous system
effects
Stimulation of -adrenergic receptors
Contributes to normal development of
CNS
In adult maintain alertness
Lethargy if hypothyroidism
Increase heart rate and force of
contraction
Elevates blood pressure
Increase cardiac output
CATABOLISM OF THYROID HORMONES

Most of the thyroid hormones are rendered

biologically inactive by removing iodine from
their structure with the help of deiodinases
Mainly through deiodination
Deiodinase
In liver, muscle and kidney
Conjugation in liver and kidney with
glucoronides and sulfates
Deiodination more common
Permits recycling of iodine
 CATABOLISM OF THYROID HORMONES

The best example is the conversion of T4 into rT3, if

the cell does not require stimulation.
To get rid of the thyronine, the liver conjugates the
molecule with a glucoronide or sulphate molecule
making it more water soluble, and possible to excrete
through the kidney into the urine.
Deiodination is usually the first step as a mechanism
to conserve and recycle iodine.
Deiodination takes place in the liver and the iodine is
released into circulation where it then reaches the
thyroid gland for further use
 REGULATION OF THYROID ACTIVITY
Two hormones from the hypothalamus and hypophysis respectively
are the main regulators of thyroid activity.
In response to low temperature the hypothalamus secretes TRH,
which reaches the thyrotropes in the hypophysis through the portal
system.
In the thyrotropes, it stimulates the production of TSH, which
through circulation reaches the thyroid gland.
Stimulates the follicular cells, which in turn are ready to secrete TH
and commence the secretory mode of these follicles.
The circulatory T3 and T4 exert a negative feedback in both the
hypothalamus to reduce TRH production, and in the pars distalis to
reduce secretion of TSH.
TH also exerts a negative feedback directly in the thyroid gland
 ABNORMALITIES RELATED TO
THYROID FUNCTION
Two types of problems may appear in relation to thyroid
function.
One has to do with deficient production of thyroid
hormones, hypothyroidism; and the other with an excess
stimulation by thyroid hormones, hyperthiroidism.
The cause for hypothyroidism can be dietary or
pathologic. In the case of a dietary induced hypothyroidism
the disease is called Goiter.
A deficiency in dietary iodine or the presence of compounds
that trap iodine, prevent the normal synthesis of TH;
therefore, in an attempt to compensate, the thyroid gland
grows disproportionately.
This is easily observed as a large mass around the front of
the neck
 EFFECTS OF
THYROXINE/TRIIODOTHYRONINE (T4, T3)

Carbohydrate Protein
Gastrointestinal Required for
glucose uptake normal growth.
increased Increased levels
Increased cause catabolism,
gluconeogenesis. especially muscle.
 T3 AND CARBOHYDRATE

GLUCONEOGENESIS
(At the Expense of Muscle)
APPETITE

T3 AND PROTEIN
INCREASED TURNOVER
LARGER INCREASE IN DEGRADATION
(Therefore, NET LOSS)
 EFFECTS OF THYROXINE/TRIIODOTHYRONINE (T4, T3)

BMR Brain Development

Increased (much of this Required for normal
due to an increase in brain development,
Na/K-ATPase). Especially nerve
myelination.
Cretinism, if hormone
is missing during
embryonic
development.
 EFFECTS OF THYROXINE/TRIIODOTHYRONINE (T4, T3)

Fat (lipid metabolism)

Mobilization of fat stores.
Blood cholesterol decreased.
Blood phospholipids decreased. are
decreased despite triglyceride mobilization
from fat stores because lipid breakdown to
make ATP is increased even more.
Many of the effects on lipid metabolism
are due to changes in Autonomic Nervous
System (ANS) function.
 EFFECTS OF THYROXINE/TRIIODOTHYRONINE (T4, T3)

Miscellaneous:
Synergistic involvement with the ANS.
High doses unmask diabetes mellitus.
High doses unmask failing heart.
Signs of Excess (hyperthyroidism): Signs of Deficit
heat intolerance (hypothyriodism):
Lipidemia
CNS changes
Cholesterolemia
sweating
Cold Intolerance
hyperglycemia
Myxedema (sometimes)
muscle catabolism Obesity
exopthalmos (possibly due to TSH) Slow Speech
cardiovascular axis activity Poor cardiovascular axis
increased but efficiency decreased function
BMR increased
 THYROID DISORDERS

HYPOTHYROIDISM (Underactive thyroid)

HYPERTHYROIDISM (Overactive Thyroid)
THYROID NODULES(Lumps)
Thyroiditis
Goiters
Thyroid Cancer
 Hyperthyroidism ~ Hyperthyroidism means too much thyroid
hormone. Current methods used for treating a hyperthyroid patient
are radioactive iodine, anti-thyroid drugs, or surgery. Each method
has advantages and disadvantages and is selected for individual
patients. Many times the situation will suggest that all three methods
are appropriate, while other circumstances will dictate a single best
therapeutic option. Surgery is the least common treatment selected
for hyperthyroidism. The different causes of hyperthyroidism are
covered in detail.

Hypothyroidism ~ Hypothyroidism means too little thyroid hormone

and is a common problem. In fact, hypothyroidism is often present
for a number of years before it is recognized and treated. There are
several common causes, each of which are covered in detail.
Hypothyroidism can even be associated with pregnancy. Treatment
for all types of hypothyroidism is usually straightforward.

Thyroiditis ~ Thyroiditis is an inflammatory process ongoing within

the thyroid gland. Thyroiditis can present with a number of
symptoms such as fever and pain, but it can also present as subtle
findings of hypo or hyper-thyroidism. There are a number of causes,
some more common than others. Each is covered on this site.
 Thyroid disorder
Goiters ~ A thyroid goiter is a dramatic enlargement of the thyroid
gland. Goiters are often removed because of cosmetic reasons or,
more commonly, because they compress other vital structures of the
neck including the trachea and the esophagus making breathing and
swallowing difficult. Sometimes goiters will actually grow into the
chest where they can cause trouble as well. Several nice x-rays will
help explain all types of thyroid goiter problems.
Thyroid Cancer ~ Thyroid cancer is a fairly common malignancy,
however, the vast majority have excellent long term survival. The
characteristics of each type of thyroid cancer and its typical
treatment, follow-up, and prognosis are very important to discus
before treatment.
Solitary Thyroid Nodules ~ There are several characteristics of
solitary nodules of the thyroid which make them suspicious for
malignancy. Although as many as 50% of the population will have a
nodule somewhere in their thyroid, the overwhelming majority of
these are benign. Occasionally, thyroid nodules can take on
characteristics of malignancy and require either a needle biopsy or
surgical excision. Now includes risks of radiation exposure and the
role of Needle Biopsy for evaluating a thyroid nodule. Also a new page
on the role of ultrasound in diagnosing thyroid nodules and masses.
The symptoms of thyroxin production
 (Thyrotoxicosis or toxic goiter )

Excessive secretion of TSH ,TRH

TSI = Thyroid Stimulating Immunoglobulin

The symptoms of hyperthyroidism
Every function of the body tends to speed up.
Nervousness, irritability, increased perspiration,heart racing,
hand tremors, anxiety, difficulty sleeping,thinning of your skin,
fine brittle hair and weakness in musclesespecially in the
upper arms and thighs.
Have more frequent bowel movements, but diarrhea is
uncommon.
Lose weight despite a good appetite and, for women, menstrual
flow may lighten and menstrual periods may occur less often.
Since hyperthyroidism increases metabolism, many individuals
initially have a lot of energy.
In the hyperthyroidism continues, the body tends to break down,
so being tired is very common
 Causes hyperthyroidism

Thyrotoxicosis or toxic goiter : Immune system

(autoimmune disorder)
a viral infection that causes the gland to leak
stored thyroid hormone
Thyroid neoplasm (thyroid neoplasia)
Excessive secretion of TSH ,TRH
Excessive exogenous administration of thyroxin
Regulation of Tyroxin (T3/T4)
THYROXIN SYNTHESIS IN THE FOLLICULAR CELL
Diagnosis of thyroid dysfunction

1. Thyroid function testing

2. Antibody testing
3. Radionuclide scanning
1. Thyroid function test interpretation
 2. Antibody testing

The most sensitive in-vitro index for this is

measurement of thyroid peroxidase
antibody level,but this can occasionally
give false negative results (eg, in juvenile
autoimmune thyroiditis).
In primary hypothyroidism, a raised level
of thyroid peroxidase antibody is evidence
for autoimmune chronic lymphocytic
thyroiditis
 3. Radionuclide scanning

Radionuclide thyroid scanning is not

routinely necessary for diagnosing Graves
disease or toxic multinodular goiter, but is
useful when the cause of hyperthyroidism
is not apparent (eg, when no goiter is
palpable, when neck pain or tenderness
suggests subacute thyroiditis, or when a
solitary hot nodule is suspected)
Table Comparison of T4 and T3 in plasma

2.24

0.40
 Differential Diagnoses
Euthyroid Hyperthyroxinemia
Goiter
Goiter, Diffuse Toxic
Graves Disease
Thyrotoxicosis
 Euthyroid Hyperthyroxinemia
Euthyroid hyperthyroxinemia is defined as
a condition in which the serum total or,
rarely, the free thyroxine (T4)
concentrations are abnormal without
evidence of clinical thyroid disease.
These changes may be transient or
persistent and may be associated with
normal, low, or high triiodothyronine (T3)
levels
 Goiter
enlargement of the thyroid gland.
inefficient in making thyroid hormones, inflamed, or
occupied by tumors.
Thyroid gland enlargement can be generalized and
smooth, a so called diffuse goiter.
if growth of one or more discrete lumps (nodules) within
the gland, called nodular goiter.
Goiter with proper amounts of thyroid hormones, called
a euthyroid or nontoxic goiter;
goiter with overproduction of thyroid hormone, called
toxic goiter,
goiter with sufficient thyroid hormones, called goitrous
hypothyroidism
 Diffuse Toxic Goiter
The thyroid gland is diffusely hyperplastic
and excessively overproduces thyroid
hormone.
This results in accelerated metabolism in
most body organs.
associated with clinical evidence of
oculopathy, or rarely with
dermopathy/acropathy, the term Graves
disease is often applied.
 Graves Disease
an autoimmune disease that causes hyperthyroidism.
The immune system activation targets the thyroid gland
and causes overproduction of thyroid hormones (T3 &
T4) in blood
Graves' disease occurs in 1-2 % of the hyperthyroidism
population.
Examination of the neck may show thyroid enlargement
or goiter, Physical examination shows an increased heart
rate along with tremor, TSH decreased T3 & T4
increased, Radioactive iodine uptake increased, TSI
(Thyroid stimulating immunoglobulin) increased
with a T3/ T4 ratio of greater than 20.
 Thyrotoxicosis
Biochemical and physiologic complex
when excessive serum levels of
thyroid hormone are present
That results when thyroid gland
overproduces thyroid hormone
With a T3/ T4 ratio of less than 15