University of Diyala

College of Medicine
2nd Stage

Biochemistry Report

Repot title:
Thyroid Hormones

By:
Abdullah Essa Raham Jassim

Supervised By:
Dr. Omar Jassim

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 Introduction
The thyroid gland is an endocrine organ consisting of two connected lobes that are
found situated on the trachea, just inferior to the thyroid cartilage (Adam’s apple).
The principle thyroid hormones that regulate functions in the body are thyroxine
(T4) and triiodothyronine (T3). T4 is mainly inactive, and is converted
peripherally in the body to make the more active T3. T3 and T4 are synthesized
from iodine and tyrosine. Thyroxine (T4), tri-iodothyronine (T3) and calcitonin are
secreted by the thyroid gland. Both T4 and T3 are products of the follicular cells
and influence the rate of all metabolic processes. Calcitonin is produced by the
specialized C cells and influences calcium metabolism

Thyroid Hormone Synthesis

There are six steps in the synthesis of thyroid hormone, and you can remember
them using the mnemonic ATE ICE:

 Active transport of Iodide into the follicular cell via the Sodium-Iodide Symporter
(NIS). This is actually secondary active transport, and the sodium gradient driving
it is maintained by a Sodium-Potassium ATPase.
 Thyroglobulin (Tg), a large protein rich in Tyrosine, is formed in follicular
ribosomes and placed into secretory vesicles.
 Exocytosis of Thyroglobulin into the follicle lumen, where it is stored as colloid.
Thyroglobulin is the scaffold upon which thyroid hormone is synthesised.
 Iodination of the Thyroglobulin. Iodide is made reactive by the enzyme thyroid
peroxidase. Iodide binds to the benzene ring on Tyrosine residues of
Thyroglobulin, forming mono-iodotyrosine (MIT) then di-iodotyrosine (DIT).
 Coupling of MIT and DIT gives the Triiodothyronine (T3) hormone and coupling
of DIT and DIT gives the Tetra-iodothyronine (T4) hormone, also known
as Thyroxine.
 Endocytosis of iodinated thyroglobulin back into the follicular cell. Thyroglobulin
undergoes proteolysis in lysosomes to cleave the iodinated tyrosine residues
from the larger protein. Free T3 or T4 is then released, and the Thyroglobulin
scaffold is recycled.

T3 and T4 are the active thyroid hormones. They are fat soluble and mostly
carried by plasma proteins – Thyronine Binding Globulin and Albumin. While T3
is the more potent form, it also has a shorter half-life due to its lower affinity for

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the binding proteins. Less than 1% of T3 and T4 is unbound free hormone. At the
peripheries, T4 is deiodinated to the more active T3.

T3 and T4 are deactivated by removing iodine. This happens in the liver and
kidney. As T4 has a longer half-life, it is used in the treatment of hypothyroidism
over T3 as its plasma concentrations are easier to manage.

Control of thyroid-stimulating hormone secretion

Thyroid-stimulating hormone stimulates the synthesis and release of thyroid
hormones from the thyroid gland. Its secretion from the anterior pituitary gland is
controlled by thyrotrophin-releasing hormone (TRH) and circulating
concentrations of thyroid hormones.

Effect of thyrotrophin-releasing hormone

Pituitary TSH synthesis and release are stimulated by TRH, a tripeptide produced
in the hypothalamus and released into the portal capillary plexus. The action of
TRH can be over-ridden by high circulating free T4 (fT4) concentrations, and

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therefore exogenous TRH has little effect on TSH secretion in hyperthyroidism.
Once TRH reaches the pituitary, it binds to TRH receptors, members of the seven
transmembrane-spanning receptor family, which are coupled to G proteins.

Effects of thyroid hormones in the control of TSH secretion

Thyroid hormones reduce TSH secretion by negative feedback. Tri iodothyronine
binds to anterior pituitary nuclear receptors. In the anterior pituitary gland, most
of the intracellular T3 is derived from circulating fT4. Therefore this gland is more
sensitive to changes in plasma T4 than to T3 concentrations.

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 Normal thyroid gland homeostasis
The thyroid gland is situated in the anterior triangle of the neck and is responsible
for the production of thyroxine (T4) and triiodothyronine (T3). It mostly originated
from endodermal cells, but it also has some neural crest cell components scattered
throughout the gland as well.

Although it is the largest endocrine gland, it is a relatively small structure, weighing

between 15 – 20 g. With the onset of puberty, a gender disparity arises regarding
the size of the gland; where females have slightly larger glands than males. The
function of the gland is regulated directly by the pituitary gland (thyroid stimulating
hormone secretion [thyrotropin], TSH) and indirectly by
the hypothalamus (thyrotropin releasing hormone, TRH). The hypothalamus and
pituitary gland also responds to elevated serum levels of thyroid hormones by
decreasing the release of TRH and TSH, respectively.

Hormonal output from the thyroid is regulated by negative feedback. Beginning

from the hypothalamus, thyrotropin-releasing hormone (TRH) is released, which
results in the production of thyroid-stimulating hormone (TSH) by the
anterior pituitary that in turn stimulates production of T3 and T4. Excess amounts
of T3 and T4 provides negative feedback at both the level of the anterior pituitary
and hypothalamus.

Functions (Effects) of Thyroid Hormones

 Increase Basal Metabolic Rate (BMR),
 Increase Oxygen consumption,
 Increase Thermogenesis (heat production in the body),
 Activate Na+-K+-ATPase in cells,
 Increase number of Mitochondria in cells,
 Increase mobilization of endogenous: Carbohydrate, Fat and Protein as
substrates for energy metabolism,
 Increase Glycolysis, Glycogenolysis, Gluconeogenesis,
 Increase Lipolysis and Protein degradation,
 Decrease Muscle mass,
 Decrease Adipose Tissue,
 Increase Beta-Adrenergic receptors, which leads to increase Cardiac
Output,

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  Increase Systolic blood pressure only,
 Increase Ventilation Rate,
 Required for maturation of Ovary and Testis,
 Required for Actions of Growth Hormone (GH) to promote linear growth /
bone formation,
 Required for development of CNS in Fetus

Disorders of Thyroid Gland

Hyperthyroidism
Hyperthyroidism is the medical term for an overactive thyroid gland. One common
cause of Hyperthyroidism is Grave’s Disease – an autoimmune condition where
antibodies are produced that stimulate the TSH receptors on follicular cells. It affects
roughly 1% of the population and is 10 times more common in women than in men.
Patients may present with heat intolerance, weight loss, tachycardia, nervousness,
increased sweating, exophthalmos and increased bowel
movements. Hyperthyroidism can be treated with Carbimazole which inhibits iodine
binding to thyroglobulin.

Hypothyroidism
Hypothyroidism is an underactive thyroid gland. One common cause of
Hypothyroidism is Hashimoto’s Disease – an autoimmune condition where thyroid
follicles are destroyed or antibodies are produced that block the TSH receptor on
follicle cells.

Like hyperthyroidism, roughly 1% of the population is affected with it being 10 times

more common in women than in men. In the developing world, the most common
cause of Hypothyroidism is iodine deficiency.
Patients can present with cold intolerance, weight gain, bradycardia, poor
concentration, myxoedema, dry skin, some hair loss and
constipation. Hypothyroidism can be treated with oral T4 tablets (100-200 µg/day),
to replace the hormone that is not being produced by the body.

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 One way to remember the associated diseases with hyperthyroidism and
hypothyroidism is to look at the prominent vowels in each: hyperthyroidism is caused
by Grave‘s disease, whereas hypothyroidism is caused by Hashimoto’s disease.

Conclusion
The thyroid gland is important in regulating metabolism. It produces 2 important
metabolic hormones, thyroxine (T4) and triiodothyronine (T3). T4 contains 4 iodine
atoms, whilst T3 contains 3 iodine atoms. T3 and T4 both affect the body’s
metabolism by influencing protein production of every cell in the body. This protein
production in turn affects tissue growth, temperature, energy use, and heart
rate. The thyroid gland also produces calcitonin, which is an antagonist to
parathyroid hormone.

References:
1. https://teachmephysiology.com/endocrine-system/thyroid-parathyroid-
gland/thyroid-gland/
2. Harper’s Illustrated Biochemistry 26th Edition; 2003; Ed. By R. K. Murray et. al.
3. Biochemistry, By V. L. Davidson & D. B. Sittman. 3rd Edition.
4. Textbook of Biochemistry with Clinical Correlations 4th Edition.