Thyroid gland

The thyroid is in the front part of the lower neck. It's

shaped like a bow tie or butterfly. It makes the thyroid hormones thyroxine
and triiodothyronine . These hormones control the rate at which cells burn
fuels from food to make energy. The more thyroid hormone there is in the
bloodstream, the faster chemical reactions happen in the body.

follicular cells of the thyroid gland produce and secrete T3 and T4 in

response to elevated levels of TRH, produced by the hypothalamus, and
subsequent elevated levels of TSH, produced by the anterior pituitary gland,
which further regulates the metabolic activity and rate of all cells, including
cell growth and tissue differentiation.

The thyroid gland develops from two different clusterings of embryonic cells. One
part is from the thickening of the pharyngeal floor, which serves as the precursor of
the thyroxine (T4) producing follicular cells. The other part is from the caudal
extensions of the fourth pharyngobranchial pouches which results in the
parafollicular calcitonin-secreting cells. These two structures are apparent by 16 to
17 days of gestation. Around the 24th day of gestation, the foramen cecum, a thin,
flask-like diverticulum of the median anlage develops. At approximately 24 to 32
days of gestation the median anlage develops into a bilobed structure. By 50 days
of gestation, the medial and lateral anlage have fused together. At 12 weeks of
gestation, the fetal thyroid is capable of storing iodine for the production of TRH,
TSH, and free thyroid hormone. At 20 weeks, the fetus is able to implement
feedback mechanisms for the production of thyroid hormones. During fetal
development, T4 is the major thyroid hormone being produced while
triiodothyronine (T3) and its inactive derivative, reverse T 3, are not detected until
the third trimester.
Parathyroid glands

Attached to the thyroid are four tiny glands that work together called the
parathyroids (pronounced: par-uh-THY-roydz). They release parathyroid
hormone, which controls the level of calcium in the blood with the help of
calcitonin (pronounced: kal-suh-TOE-nin), which the thyroid makes.

A lateral and ventral view of an embryo showing the third (inferior) and fourth
(superior) parathyroid glands during the 6th week of embryogenesis

Once the embryo reaches four weeks of gestation, the parathyroid glands begins to
develop. The human embryo forms five sets of endoderm-lined pharyngeal
pouches. The third and fourth pouch are responsible for developing into the
inferior and superior parathyroid glands, respectively. The third pharyngeal pouch
encounters the developing thyroid gland and they migrate down to the lower poles
of the thyroid lobes. The fourth pharyngeal pouch later encounters the developing
thyroid gland and migrates to the upper poles of the thyroid lobes. At 14 weeks of
gestation, the parathyroid glands begin to enlarge from 0.1 mm in diameter to
approximately 1 – 2 mm at birth. The developing parathyroid glands are
physiologically functional beginning in the second trimester.

o Epithelial cells of the parathyroid glands are richly supplied with

blood from the inferior and superior thyroid arteries and secrete
parathyroid hormone (PTH). PTH acts on bone, the kidneys, and the
GI tract to increase calcium reabsorption and phosphate excretion. In
addition, PTH stimulates the conversion of Vitamin D to its most
active variant, 1,25-dihydroxyvitamin D3, which further stimulates
calcium absorption in the GI tract.[3]

Thyroid Gland
Thyroid gland is a part of the body's endocrine system. It is the largest organ
specialized for endocrine function in human body. It is a butterfly - shaped gland
Fig (1). It is an organ with many veins, anchored around the front of th e throat
near the voice box . The gland is essential to normal body growth in infancy and
childhood. It absorbs iodine from the diet and releases thyroid hormones -iodine-
containing compounds that help govern the rate of body's metabolism. Its total
processes ,controlling body temperature, regulating protein, fat and carbohydrate
catabolism in all cells.
Thyroid keep up growth hormone release, skeletal maturation, and heart rate ,force
and output . It promotes central nervous system growth and stimulate synthesis of
many enzymes, Thyroid is necessary for muscle tone and vigor .To a high degree,
metabolism is regulated by the hormone thyroxine, which can be made by the
thyroid if enough organic iodine is available.
The thyroid gland
Thyroid hormones
Thyroid contains two hormones, L-thyroxine (T4, tetraiodothyronine) and
Ltriiodothyronine (T3), Thyroid hormones are synthesized in the thyroid gland by
iodination and coupling of two molecules of the amino acid tyrosine, a process that
is dependent on an adequate supply of iodide .
Iodine is an indispensable component of the thyroid hormones, comprising 65% of
T4’s weight, and 58% of T3’s. The thyroid hormones are the only iodine
containing compounds with established physiologic significance in vertebrates .
The most obvious overall effect on metabolism is to stimulate the basal metabolic
rate (BMR), but the precise molecular basis of this action is not known.
The only known action is that controlling the basal metabolic rate which depends
on the conversion rate of T4 to T3in health individuals.
These two hormones are acted through entering the cells and binding to specific
receptors in the nuclei, where they stimulate the synthesis of a variety of species of
mRNA, thus stimulating the synthesis of polypeptides including hormones and
enzymes in the cytoplasmi, they also increase the sensitivity of the cardiovascular
and nervous systems to catecholamine.
The activity of the thyroid gland is predominantly regulated by concentration of
pituitary glycoprotein hormone, thyroid stimulating hormone (TSH).
The normal plasma concentrations of T4 and T3 are 60-150 nmol/L and 1.0-2.9
nmol/L, respectively. More than 99% of plasma T 4 and T3 is protein bound,
mainly to an α-globulin, thyroxine- binding globulin (TBG), and to less extent to
albumin and thyroxine-binding prealbumin. The free unbound fraction of both
hormones are the physiologically active forms which regulate TSH secretion from
the anterior pituitar..
T3 and T4 are released into the circulation, approximately 10 g of T3 and 100g of
T4 are released into the blood stream, and about 25g of T3 are produced daily by
conversion of T4 into T3 in peripheral tissue.
The conversion of T4 to T3 takes place in a number of locations in the body, the
main place is the liver, T3 is derived when the enzyme deiod inase removes one
iodine atom from T4
Effect of thyroid hormone on specific bodily mechanisms in human body [:
 Stimulation of carbohydrate metabolism.
 Stimulation of fat metabolism.
 Stimulation of protein metabolism.
 Effect on plasma and liver fats.
 Increase requirements for vitamins.
 Increase basal metabolic rate (BMR).
 Effect on cardiovascular system.
 Excitatory effect on the central nervous system.
 Effect on sleep.
 Effect on other endocrine glands.
 Effect on sexual function.

Regulation of thyroid hormones secretion:

The right amount of thyroid hormones must be secreted at all times to maintain
normal levels of metabolic activity in the body, to achieve this, specific feedback
mechanisms operate through the hypothalamus and anterior pituitary gland to
control the rate of thyroid secretion by a specific mechanism Fig . TSH (thyroid
stimulating hormone) is also known as thyrotropin. It is a hormone from the
anterior pituitary gland which increases thyroid secretion. TSH is a glycoprotein
with a molecular weight of about 28.000 Dalton.
The secretion of TSH from the anterior pituitary gland is controlled by:
 Circulating concentration of thyroid hormones.
 Thyrotrophin-relasing hormones (TRH).

The effect of thyroid hormones is to reduce TSH secretion by negative feedback

were T3 which binds to anterior pituitary nuclear receptors. In the anterior pituitary
gland most of the intracellular T3 is derived from circulating free T4. Therefore
this gland is more sensitive to changes in plasma T4 than T3concentrations.
Secretion and control of thyroid hormones.
Thyroid-stimulating hormone (TSH):
The history of TSH began with the discovery of thyroid-stimulating activity in the
pituitary gland. Edward Uhlenhuth from the University of Maryland Medical
School was the first to demonstrate that the anterior lobe of the pituitary gland
secreted a thyroid stimulator using several species of salamanders (Amphibiaus),
He showed that injection of bovine pituitary extracts caused a clear histological
stimulation of thyroid gland. In 1929 Leo Loeb and Max Aaron working
independently confirmed Uhlenhuth’s results using guinea pigs (mammals). These
initial findings were followed in the 1960s by the purification TSH and in the
early 1970s by the determination of the primary structure of the TSH subunits. In
the 1980s, the cloning of the human δ-subunit and TSH δ-subunit genes, were the
important milestones in studying TSH expression, regulation, and action from the
basic science stand point , another major breakthrough occurred in 1994 with the
elucidation of the crystal structure of the closely related human Chorionic
Gonadotropin (CHG), which indicated that the glycoprotein hormones belong to
the super family of Cystine-Knot Growth Factors (CKGF).
Then in 1966 it was found that TSH exerts its biological effects by binding to a
protein on the thyroid cell plasma membrane.
TSH is a glycoprotein synthesized and secreted from thyrotrophs (basophile cell)
of the anterior pituitary gland. TSH is a member of the glycoprotein hormone
family that includes Follicle stimulating hormone (FSH), Lutenizing hormone(LH)
and (CHG).
Specific effects of TSH on the thyroid gland:
Effects on the thyroid gland is increases the secretion of thyroxine and
triiodothyronine by the thyroid gland. Its specific effects on the thyroid gland are
as follow:
 Increased proteolysis of the thyroglobulin that has already been stored in the
follicles, with resultant release of the thyroid hormones into the circulating blood
and diminishment of the follicular substance itself.
 Increased activity of the iodide pump, which increases the rate of “iodide
trapping” in the glandular cells, sometimes increasing the 9 ratio of intracellular to
extracellular iodide concentration in the glandular substance to as much as eight
times normal.
 Increased iodination of tyrosine to form the thyroid hormones.
 Increased size and increased secretary activity of the thyroid cells.
 Increased number of thyroid cells plus a change from cuboidal to columnar cells
and much in folding of the thyroid epithelium into the follicles .

Disorders of the thyroid gland:

The metabolic manifestations of the thyroid disease related to either excessive or
inadequate production of thyroid hormones (hyperthyroidism and hypothyroidism,
respectively).
Hyperthyroidism (Thyrotoxicosis):
An abnormal condition of the thyroid gland resulting in excessive secretion of
thyroid hormones characterized by an increased metabolism and weight loss .
The major causes and clinical features of hyperthyroidism are:
 Grave’s disease
 Toxic multinodular goitre (Solitary toxic adenoma thyroiditis
 Exogenous iodine and iodine-containing drugs,e.g. amiodarone
 Excessive T4 or T3 ingestion
 Ectopic thyroid tissue,
 e.g. struma ovarii
 functioning metastatic thyroid cancer HCG dependent
 e.g. choriocarcinoma, pituitary tumour (very rare)
 Clinical Features
 Weight loss (but normal appetite)
 Sweating, heart intolerance
 Fatigue
 Palpitation: sinus tachycardia or atrial fibrillation angina, heart failure (high
output)
 Agitation, tremor
 Generalized muscle weakness,
 Proximal myopathy
 Diarrhoea
 Oligo menorrhoea, infertility
 Goitre
 Eyelid retraction, Lid lag

Hypothyroidism:
Table (2): Causes and clinical features of hypothyroidism
There are many causes of primary hypothyroidism table . Hypothyroidism, like
hyperthyroidism, probably is initiated by autoimmunity against the thyroid gland,
but immunity that
destroys the gland rather than stimulates . Clinical diagnosis is confirmed by the
finding of a high plasma TSH concentration (Unless the condition is secondary to
hypopituitarism) and low free T4 (FT4) concentration .
Albumin
Albumin is the most abundant protein found in the plasma, making up 55 -65% of
the total protein (reference range 35-50 g/L). Albumin is a small, highlysoluble,
protein with a molecular weight of 69.000Da , It has a single polypeptide chain of
580 amino acids with 17 intrachain S-S bonds .
It is synthesized primarily by the hepatic parenchymal cells . Albumin functions
include regulation of osmotic pressure , and nonspecific transport, as it binds many
non-polar compounds such as bilirubin, long-chain fatty acids and a number of
drugs. It has specific binding sites for copper ion, it also functions as a reservoir for
a number of hormones.Albumin is also an important component of plasma
antioxidant activity , primarily by binding free fatty acids, free ions, hypochlorous
acid (HOCl), and bilirubin , because of its copper-binding ability, it is a powerful
continue on the albumin surface and damage it , but there is so much albumin
present, therefore the damage is biologically insignificant, and more important
targets are protected . So albumin is required as a sacrificial antioxidant .
Albumin also reacts with HOCl , this acid damages the albumin, but this is again
probably biologically insignificant in view of albumin's high concentration and
rapid turnover .Albumin may scavenge peroxy radicals , also it can bind free fatty
acids and protect them from peroxidation .
Alanine transaminases (GPT) (EC2.6.1.2)
Also called serum glutamate-pyruvate transaminase (SGPT). Having molecular
weight approximately 101000 Dalton catalyze the reaction according to this
equation:
This reaction goes to the right to provide a source of nitrogen for the urea cycle,
the pyruvate is available for entry into the citric acid cycle.
Whereas glutamate is deaminated (catalyzed by glutamate dehydrogenase),
yielding ammonia and δ-keto glutarate . GPT is present in high concentration in
liver to lesser extent in skeletal muscle, kidney and heart , measurement of GPT
activity in serum used an indicator of hepatocellular damage .
It is used as a part of enzymes to establish whether liver damage has occurred .
Aspartate transaminase (GOT) (EC2.6.1.1):
Also called glutamate oxaloacetate transaminase (SGOT), present in high
concentration in the heart, liver, skeletal muscle, kidney and erythrocytes. Damage
to any of these tissue may increase plasma GOT levels . GOT catalyses the
following reaction:-
The reaction goes to the right . There are two form of GOT. The mitochondrial and
the soluble forms. The major diagnostic application used GOT activities are the
investigation of myocardial infarction, liver disease and muscle disease .
CONCLUSION
Thyroid gland plays a master rule in body metabolism. The right amount of thyroid
hormones must be secreted at all times to maintain normal levels of metabolic
activity in the body, to achieve this, specific feedback mechanisms operate through
the hypothalamus and anterior pituitary gland to control the rate of thyroid
secretion.