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Learning objectives:
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Hypothalamus
About 93% of the metabolically active hormones secreted by the thyroid gland is
thyroxine (T4) and 7% is triiodothyroxine (T3). However, almost all the T4 is
converted to T3 in the tissues, so both are functionally important. The function of
these two hormones is essentially the same, but they differ in the speed and
intensity of action. T3 is about four times more potent than T4, but is present in
the blood at much lower concentrations and has a much shorter half life than T4.
Iodine Requirement
Iodine is absorbed in the diet in the same way that other elements are (e.g.
Chloride). Iodides are usually rapidly excreted by the kidneys and only about one
fifth are absorbed by the thyroid gland for hormone synthesis.
The first stage in the formation of thyroid hormones is the transport of iodine
from the blood, into the thyroid follicular cell. The thyroid follicular cell has the
specific ability to actively pump iodine into the cell this is called iodine
trapping.
The rate of iodine trapping is influenced by several factors. The most important
factor is the concentration of TSH. Increased secretion of TSH leads to increased
activity of the iodine pump in thyroid cells.
Synthesis and Secretion of Thyroid Hormon
Thyroglobulin
The thyroid cells are typical protein-secreting glandular cells. The endoplasmic
reticulum synthesise and secrete into the follicles a large glycoprotein molecule
called thyroglobulin which has a molecular weight of about 335,000.
Oxidised iodine will now bind directly, but very slowly, with the amino acid
tyrosine. In the thyroid cells, the enzyme iodinase is present which causes this
reaction to occur much faster. Iodine binds to about one sixth of the tyrosine
residues available in the thyroglobulin molecule.
Synthesis and Secretion of Thyroid hormon
Synthesis and Secretion of Thyroid Hormon
Storage of Thyroglobulin
The thyroid gland is unusual among the other endocrine glands in its ability to
store large amounts of hormones. After synthesis of thyroid hormones, each
thyroglobulin molecule contains up to 30 thyroxine molecules and a few
triiodothyroxine molecules. In this form, the thyroid hormones are stored in the
follicles in an equal amount sufficient to supply the body with its normal
requirements of thyroid hormones for 2 3 months. Therefore, when synthesis of
thyroid hormones ceases, the physiological effects of deficiency are not seen for
several months.
Although much more T4 than T3 is released from the thyroid gland, during the
previous few days about half of the T4 has been converted to T3, therefore the
hormone that is used by the tissues is T3. a total of about 35 micrograms of T3 is
used by the tissues each day.
On entering the blood over 99% of T4 and T3 are bound to plasma proteins such
as thyroxine binding globuin, thyroxine binding prealbumin and albumin.
T4 and T3 are released slowly to the tissues due to the high affinity they have for
their binding proteins. Once released to the cells, the thyroid hormones bind to
proteins within the cell which allows them to be stored until required.
Thyroid hormones have a slow onset and a long duration of action. The
actions of T3 are about four times as rapid as T4
Synthesis and Secretion of Thyroid Hormon
Endothelium
Follicle Colloid Thyroid Follicular Cell
Blood
Thyroglobulin Endoplasmic Reticulum
Exocytosis
I-
[O]
I0
I0-
Pendrin
Proteolysis Na/I Symporter
Iodination Na+
Conjugation
T3
T4
Endocytosis
Physiological Functions of Thyroid Hormon
The thyroid hormone receptors are either attached to the DNA genetic
strands, or located in proximity to them. On binding with the hormone, the
receptor becomes activated and initiates the transcription process producing
messenger RNA and synthesis of proteins.
Physiological Functions of Thyroid Hormon
The thyroid hormones increase the metabolic activity in almost all of the
tissues of the body. The basal metabolic rate can increase 60 100 % above
normal when large numbers of these hormones are secreted. The rate of
utilisation of foods for energy is increased. Protein synthesis and catabolism is
increased. The rate of growth is increased in young people and the mental
processes are excited. The activity of most other endocrine glands is also
increased.
Thyroid hormones have both general and specific effects on growth. Thyroid
Physiological Functions of Thyroid Hormon
Increased thyroid hormones results in
Stimulation of fat metabolism
decreased concentration of
Stimulation of carbohydrate cholesterol, phospholipids and
metabolism
Increased blood flow and cardiac triglycerides. Free fatty acids are
output increased.
Increased heart rate and strength Increased requirement for vitamins as
Normal arterial pressure, but raised they are required as cofactors for
pulse enzymes.
Increased respiration as the utilisation Effects on other endocrine glands
of oxygen and formation of carbon Effects of Thyroid
dioxide is increased Hormones Increased basal metabolic rate due to
Increased gastrointestinal motility the increase in metabolism in all cells
(increased GI secretions and of the body
Decreased body weight (not always
movements)
Excitatory effects on the CNS seen as thyroid hormones also
To maintain normal levels of metabolic activity in the body, precisely the right
about of thyroid hormone must be secreted at all times. To achieve this, there are
specific feedback mechanisms that operate through the hypothalamus and
anterior pituitary gland to control the rate of hormone secretion.
TSH (an anterior pituitary hormone) increases the secretion of thyroxine and
triiodothyroxine by the thyroid gland. It has specific effects on the thyroid:
Increased activity of the iodine pump which increases the rate of iodine
trapping in the follicular cells
One of the best known stimuli for increasing the rate of TRH secretion from the
hypothalamus and therefore the rate of TSH secretion is exposure of an animal to
cold. This results from excitation of the hypothalamic centres for body
temperature control.
Various emotional reactions can also affect the output of TRH and TSH
excitement and anxiety greatly stimulate the nervous system and cause a
decrease in TSH secretion.
Increased thyroid hormone in the body fluids decreases secretion of TSH by the
anterior pituitary. When the rate of thyroid hormone secretion rises to about 1.75
times normal, the rate of TSH secretion falls essentially to zero. This negative
feedback mechanisms maintains an almost constant concentration of free
thyroid hormones in the circulating body fluids.
Antithyroid Substances
Thiocyanate ions decrease iodide trapping. The same pump that transports
iodide ions into the thyroid cells can also pump thiocyanate ions, perchlorate ions
and nitrate ions. Therefore, the administration of thiocyanate in high enough
concentration can cause complete inhibition of iodide transport into the
cells inhibiting the iodide trapping mechanism. The decreased availability
of iodide in the glandular cell does not stop the formation of thyroglobulin, it just
prevents iodination of tyrosine residues and therefore blocks thyroid
hormone synthesis. Deficiency of thyroid hormones leads to increased secretion
of TSH which causes overgrowth of the thyroid gland even though the gland still
doesnt form adequate quantities of thyroid hormones. The use of thiocyanates can
lead to the development of a greatly enlarged thyroid gland, which is called a
goiter.
Antithyroid Substances
Non-thyroidal illness
Subclinical hyperthyroidism Hyperthy Central hypothyroidism
Recent treatment for hyperthyroidism roid Isolated TSH deficiency
Drugs (e.g. Steroids)
Non-thyroidal illness FT4/FT3
FT4/FT3 N TSH FT4/FT3
TSH TSH N or
Euthyroid
FT4/FT3 N
TSH N FT4/FT3
FT4/FT3 N
TSH N or
TSH Hypothyr
oid
Subclinical hyperthyroidism FT4/FT3 Assay interference
Poor compliance with thyroxine Thyroxine replacement therapy
TSH
Malabsorption of thyroxine Poor compliance
Drugs (e.g. Amiodarone) Drugs (e.g. Amiodarone)
Assay interference Non-thyroidal illness
Non-thyroidal illness Neonatal period
TSH resistance TSH-secretion pituitary adenoma
Resistance to thyroid hormone
Disorders of thyroid hormone transpo
or metabolism
Diseases of the Thyroid
Hyperthyroidism
Most of the effects are obvious from what we have discussed already, however
some specific effects should be mentioned.
Causes of Hyperthyroidism
Symptoms of Hyperthyroidism
The symptoms are a direct result of excess secretion of thyroid hormones and
include:
Exopthalmos
Diagnosis
Treatment of Hyperthyroidism
The most direct treatment is surgical removal of the thyroid gland followed by
pharmacological replacement of thyroxine.
Patients may also be treated with radioactive iodine which destroys the thyroid
gland tissue. The patients then take thyroxine.
It is also possible to treat via a block and replace method. The patient takes a
drug that blocks thyroid hormone secretion (such as carbimazole) and then
replace the thyroid hormone using synthetic thyroxine.
Diseases of the Thyroid
Hypothyroidism
Causes of Hypothyroidism
Symptoms of Hypothyroidism
Myxedema
This develops in patients with almost total lack of thyroid hormone function.
The patient develops bagginess under the eyes and general swelling of the face.
These patients have an odematous appearance throughout the body.
Diseases of the Thyroid
Diagnosis of Hypothyroidism
Treatment of Hypothyroidism
Treatment of both hypo and hyperthyroidism removes all the symptoms the
patient experienced before treatment and they can live a long healthy life.