THYROID & PARATHYROID

HORMONES
SUBMITTED TO : DR. Muhammad Awais
SUBMITTED BY : PHARMA BUDDIES
 OUTLINE

 Introduction Of Gland
 Chemistry Of Hormone Secreted By Particular Gland
 Biosynthesis Of Hormones
 Physiological Functions Of Hormone
 Disorders Of Deficiency Or Overproduction Of Hormones
 Thyroid gland

 Thyroid gland is an endocrine gland in your neck.

It makes two hormones that are secreted into the
blood: thyroxine (T4) and triiodothyronine T3.
 Shape : a small butterfly shaped gland.
 Thyroid is larger in females than in males.
LOCATION OF THYROID GLAND

 Thyroid gland is located in neck under

skin.
 It consist of two lobes left and right Which
are connected by a central isthmus
anteriorly this produces a butterfly shape
appearance .the lobes of thyroid gland are
wrapped around the cricoid cartilage and
superior rings of the trachea .The thyroid
gland and pituitary gland work together.
HORMONES OF THYROID GLAND

 Thyroid gland Secretes 3 hormones T4 T3 and calcitonin.

 T4 is otherwise known as thyroxine and it forms about
90% of the total secretion where as T3 is only 9 to 10%.
 Calcitonin also plays role as PTH hormone.
CHEMISTRYOF THROID HORMONES

 Both T4 and T3 are iodine containing derivatives of amino acid

thyrosine.
 The hormones T4 ,T3 and reverse T3 are iodinated amino acid
tyrosine. The iodine in thyroxine accounts for 80% of the
organically bound iodine in thyroid Venous blood. Small amounts
of reverse tri- iodothyronine , monoiodotyrosine and other
compound are liberated.
STRUCTURE OF THYROID HORMONES
HALF LIFE AND RATE OF SECRETION

 Thyroid hormones have long half life. T4 has a long half life of
seven days . Half life of T3 is varying between 10 and 24 hours.

RATE OF SECRETION
POTENCY OF THROID HORMONES

 The potency of T3 is four times more than that of T4. T4 acts for
longer period than T3 .Duration of T4 action is four times more
than T3 action. This is because of the difference in the affinity of
these hormones to plasma proteins. T3 has less affinity for plasma
proteins and combines loosely with them, so that it is released
quickly. T4 has more affinity and strongly binds with plasma
proteins, so that it is released slowly. Therefore T3 act on the target
cell immediately and T4 acts slowly.
 METABOLISM OF THROID HORMONES

 Metabolism of thyroid hormones occur in muscles

,liver and kidney which we explain later…….
 BIOSYNTHESIS OF THYROID
HORMONES
 Iodine is essential for the synthesis of thyroid
hormones. More than half of the body’s total
iodine content is found in the thyroid gland.
 Biosynthesis takes place in five steps which has explained
as below :
 1- UPTAKE OF IODIDE

 The uptake of iodide by the thyroid gland occurs against a

concentration gradient (about 20 : 1).
 It is an energy requiring process and is linked to the ATPase
dependant Na+-K+ pump. Iodide uptake is primarily controlled by
TSH.
 Anti-thyroid agents such as thiocyanate and perchlorate inhibit
iodide transport.
2 – FORMATION OF ACTIVE IODINE

 The conversion of iodide (I–) to active iodine (I+) is an

essential step for its incorporation into thyroid hormones.
 Thyroid is the only tissue that can oxidize I– to a higher
valence state I+. This reaction requires H2O2 and is
catalyzed by the enzyme
thyroperoxidase (mol. wt. 60,000). An NADPH
dependent system supplies H2O2.
3 – THYROGLOBULIN & SYNTHESIS OF
T3 & T4
 Thyroglobulin (mol. wt. 660,000) is a glycoprotein and
precursor for the synthesis of T3 and T4. Thyroglobulin
contains about 140 tyrosine residues which can serve as
substrates for iodine for the formation of thyroid hormones.
 Tyrosine (of thyroglobulin) is first iodinated at position 3 to
form monoiodotyrosine (MIT) and then at position 5 to form
diiodotyrosine (DIT).
 Two molecules of DIT couple to form thyroxine(T4). One
molecule of MIT, when coupled with one molecule of DIT,
triiodothyronine (T3) is produced. The mechanism of
coupling is not well understood.
3 – THYROGLOBULIN & SYNTHESIS OF T3 &
T4
 As the process of iodination is completed, each molecule of
thyroglobulin contains about 6-8 molecules of thyroxine (T4). The
ratio of T3 to T4 in thyroglobulin is usually around 1 : 10.
 4 – STORAGE AND RELEASE OF
THYROID HORMONES
 Thyroglobulin containing T4 and T3 can be stored for several months
in the thyroid gland.
 It is estimated that the stored thyroid hormones can meet the body
requirement for 1-3 months.
 Thyroglobulin is digested by lysosomal proteolytic enzymes in the
thyroid gland. The free hormones thyroxine (90%) and
triiodothyronine (10%) are released into the blood, a process
stimulated by TSH. MIT and
 DIT produced in the thyroid gland undergo de-iodination by the
enzyme deiodinase and the iodine thus liberated can be reutilized.
 5 - TRANSPORT OF THYROID
HORMONES

 Two specific binding proteins—thyroxine binding globulin

(TBG) and thyroxine binding pre-albumin (TBPA)—are
responsible for the transport of thyroid hormones.
 Both T4 and T3 are more predominantly bound to TBG. A
small fraction of free hormones are biologically active.
 T4 has a half-life of 4-7 days while T3 has about
one day.
 MODE OF ACTION OF THYROID
HORMONES
 MODE OF ACTION OF THYROID HORMONES :
 In the target cells (particularly cells of liver, muscle and kidney), most of
the T(4) is DE iodinated to form T(3), So, the true intracellular hormone
is T(3) rather than T(4), More- over, T(3) is found freely in the plasma
and T4 is usually bound with plasma proteins. So, at the site of action,
T(3) acts more quickly than T(4). T(3) also has got high binding affinity
for thyroid hormone receptor. Thyroid hormones act by activating the
genes and increasing the genetic transcription. In addition, the thyroid
hormones also act at mitochondrial level by stimulating the synthesis of
proteins and RNA.
 Sequence of events
 1. Thyroid hormones enter the nucleus of cell and bind with thyroid
hormone receptors (TR), which are either attached to DNA genetic strands or
in close proximity to them.
 2. TR is always bound to another receptor called retinoid X receptor (RXR).
Exact role of RXR is not clear. Thyroid hormones bind with receptors and
form the hormone-receptor complex
 3. This complex initiates the transcription process by activating the enzymes
such as RNA polymerase and phosphoprotein kinases.
 4. It also stimulates the synthesis of nuclear proteins. Thus, a large number of
mRNA is formed, which activate the ribosomes to synthesize the new proteins
 5. New proteins are involved in many activities including the enzymatic
action.
Physiological functions

 Action on basal metabolic rate :

 Thyroxine increases the metabolic activities in most of the
body tissues, except brain, retina, spleen, testes and lungs. It
increases BMR by increasing the oxygen consumption of the
tissues. The action that increases the BMR is called calorigenic
action.
 In hyperthyroidism, BMR increases by about 60 to 100%
above the normal level and in hypothyroidism, it falls by 20 to
40% below the normal level.
 Action on proteins

2. ACTION ON PROTEIN METABOLISM :

Thyroid hormone increases the synthesis of proteins in the cells. The
protein synthesis is accelerated by the following ways.
1. By Increasing the Translation of RNA.
2. By Increasing the Transcription of DNA to RNA.
3. By Increasing the Activity of Mitochondria.
4. By Increasing the Activity of Cellular Enzymes
ACTION ON CARBOHYDRATE
METABOLISM
 Thyroxine stimulates almost all processes involved in metabolism
of carbohydrate.
 Thyroxine:
 Increases the absorption of glucose from GI tract.
 Enhances the glucose uptake by the cells, by accelerating the
transport of glucose through the cell membrane.
 Increases the breakdown of glycogen into glucose.
 Accelerates gluconeogenesis.
DISORDERS OF THROID

 HPERTHYROIDISM
 HYPERTHYROIDISM
 GOITER
 HYPERTHYROIDISM

This is known as thyrotoxicosis.It is

associated with over production of thyroid
hormones .
Hyperthyroidism is characterized by
increased metabolic rate nervousness,
irritability, anxiety, rapid heart rate, loss of
weight, weakness,diarrhea,protrusion of
eyeball.
Hyper thyroidism is caused by Graves
disease or due to increased intake of
thyroid hormone.
 HYPOTHYROIDISM
This is due to an impairment in the function of
thyroid gland that often causes decreased
circulatory levels of T3 andT4.
 Hypothyroidisms characterized by reduced
BMR, slow heart rate , weight gain, dry
skin...etc.
 Hypothyroidism in children is associated
with physical and mental retardation,
collectively known as cretinism. In adult
hypothyroidism causes myxedema,
characterized by bagginess under the eye's
slowness in physical and mental activities.
 GOITER
 Abnormal increase in the size
of the thyroid gland is known
as goiter. Enlargement of
thyroid gland is mostly to
compensate the decreased
synthesis of thyroid hormones
and is associated with elevated
TSH . It is also caused by
deficiency or excess of iodine.
 PARATHYROID GLAND

 The parathyroid glands lie just behind the thyroid glands in the
neck. The parathyroid glands (light pink) produce parathyroid
hormone, which increases levels of calcium in the blood.
 Each parathyroid gland is covered by a connective tissue from
which a delicate septa penetrates and divides the cells of gland into
two small clusters.
 The cells are of two types
1- chief cells
2- oxyphil cells
Chief cells & Oxyphil cells

 Chief cells are most numerous small in size and they

secrete a hormone called parathyroid hormone and
parathromone.
 This hormone raises calcium level by
1 – stimulating bone resorption by the bone cells
2 – decreasing the renal excretion of calcium by stimulating
resorption of calcium ions in kidney tubules.
Oxyphil cells

 Less numerous but larger in size.

 Its cytoplasm is acidophilic because of presence
of larger number of mitochondria.
 No secretory granules present in them and
function of these cells is unknown.
Hormones secreted by parathyroid
gland
Parathyroid gland secretes two hormones :
Parathromone
Calcitonin
Parathyroid hormone (PTH)

Chemistry
 Parathormone is a linear polypeptide
consisting of 84 amino acids. N-terminal
amino acid is alanine and C-terminal is
glutamine. PTH has molecular weight of
9500g. Parathormone from different species
differ only slightly in structure.
 BIOSYNTHESIS OF PTH

 PTH is initially synthesized in chief cells as a pro-hormone.

 Pre-Pro PTH: Consisting of 115 amino acids is first formed in
polysomes , adhering on the rough ER membrane
 Pro-PTH: Before the formation of Pre-Pro PTH is completed, its
N-terminal end protrudes into the lumen of rough ER and a
signal peptidase of rough ER membrane hydrolyzes the molecule
to split off 25 a.a. and thus pre-pro PTH is changed to pro-PTH
having 90 amino acids.
 BIOSYNTHESIS OF PTH
 PTH: Pro-PTH is transferred to rough ER lumen and moves to
Golgi cisternae. A "trypsin-like" enzyme, called Clipase B
hydrolyzes its N terminal end amino acids and remove 6 amino
acids, rich in basic amino acids, thus converting Pro-PTH to PTH.
 PTH thus formed is packaged and stored in secretory vesicles.
Increased c-AMP concentration and a low Ca level stimulates its
release from secretory vesicles. On the other hand, a high
concentration of Ca stimulates the degradation of the stored
PTH in secretory vesicles instead of its release .
 Mode of Action
 PTH increases serum Ca" level by acting on bones, kidney and intestines
 (a) Increasing Cyclic AMP Level: PTH binds to "specific receptor on the
plasma membrane of bone cells, renal tubule cells, it activates the adenyl
cyclase to form c AMP in the cells, c-AMP acts as the "second messenger"
which activates specific c-AMP dependant protein kinases, which
phosphorylate and thereby modulate the activities of specific proteins in the
bone cells and kidney cells.
 (b) Role of Ca : c-AMP also increases the Ca concentration in these cells,
which in turn may act as "messenger" to modulate the activities of some
intracellular proteins.
 (c) pH change in Tissues: The hormone increases the amounts of both L.A and
citric acid in the tissues an both of these acids may act to aid bone resorption .
 METABOLIC ROLE OF PTH
 The actions of PTH are reflected in the consequences of:
• its administration
• removal of the parathyroid glands
A. The major metabolic consequences of administration of PTH are :
• Increase in serum Ca++ concentration .
• Decrease in serum inorganic PO4 concentration.
• Increased urinary Ca++ ↑ following an initial decrease.
• . Increased urinary PO4 .
• Removes Ca from bones, particularly if dietary intake of Ca is inadequate.
• Increase in 'citrate content of blood plasma , kidney and bones.
• Activates vitamin D in renal tissue by increasing the rate of conversion of 25-OH-
cholecalciferol to 1,25- di-OH-cholecalciferol, by stimulating a-1- hydroxylase enzyme.
ACTION ON DIFFERENT ORGANS

 1 – ACTION ON INTESTINAL MUCOSA

PTH does not act directly on intestinal mucosal cells
as the cells not possess the specific receptors for PTH
.
But it increases the absorption of Ca and PO4
through production 1-25, di-OH-cholecalciferol
(calcitriol).
 2 – ACTION ON KIDNEY

 PTH acts through by increasing C-AMP. PTH binds to specific

receptors' on plasma membrane of renal cortical cells of both proximal
and distal tubules and stimulates adenyl cyclase to produce c-AMP. c-
AMP then is transported to apical/luminal part of the cell where it
activates c-AMP dependant protein kinase, which phosphorylates
specific proteins of the apical membrane to affect the several mineral
transport, across the membrane.
 PTH decreases the transmembrane transport and reabsorption of
filtered Pi in both proximal and distal tubular cells and increases the
urinary excretion of inorganic phosphate 1 (phosphaturic effect ).
 ACTION ON KIDNEY

 Fall in serum inorganic PO4 level leads to mobilization of PO4 from bones,
which also mobilizes Ca++ along with, resulting to hypercalcaemia.
 PTH stimulates a-hydroxylase enzyme located in mitochondria of proximal
convoluted tubule cells, which converts 25-OH-cholecalciferol, to 1-25, di-
OH-cholecalciferol which in turn increases the intestinal and renal
absorption of Ca resulting to hypercalcaemia.
 PTH inhibits the transmembrane transport of K and HCO3 decrease their
reabsorption by renal tubules.
 PTH increases the transmembrane transport and reabsorption of filtered Ca +
+ in the distal tubules resulting initially to decrease urinary excretion of Ca+
+ . But later on, PTH-induced hypercalcaemia enhances the amount of filtered
 3- ACTION ON BONES

 PTH binds to specific 'receptors' present on membranes of

osteoclasts, osteoblasts and osteocytes and increases cyclic AMP level
in these cells, which acts through c-AMP dependant protein kinases.
 Following actions are seen:
• Osteoclastic activity: It stimulates the differentiation and maturation
of precursors cells of osteoclasts to mature osteoclasts.
• Osteoclastic osteolysis: PTH stimulates the osteoclasts through "second
messenger" c- AMP to increase the resorption of bones which enhances
mobilization of Ca and P from bones.
 ACTION ON BONES
 Osteocytic osteolysis:
PTH also stimulates osteocytes which increases bones resorption thus
mobilizing Ca++ and Pi .There occurs enlargement of bone lacunae.
 Action on alkaline phosphatase: Alkaline phosphatase activity varies as per
PTH concentration. At low concentrations, PTH the sulfation of cartilages
and increases number of osteoblasts and alkaline phosphatase activity of
bone osteoblasts. At higher level of physiological concentrations, PTH
alkaline phosphatase activity and collagen synthesis in osteoblasts and
decreases the Ca retaining capacity of bones. PTH induces rise in
intracellular c-AMP in osteoclasts osteocytes leads to secretion of
Lysosomal hydrolases/and collagenases which increases breakdown of
collagen.
DISORDERS OF PTH

 HYPERPARATHYROIDISM
 HYPOPARATHYYROIDISM
 PARATHYROID CANCER
 HYPERPARATHYROIDISM

 Too much PTH in your blood, which can

cause your calcium levels to rise
and lead
to bone and organ damage.
 HYPOPARATHYROIDISM

 Not enough PTH into your blood,

which can lead to low calcium and
high phosphorous.
 PARATHYROID CANCER

 Parathyroid cancer is a rare disease in

which malignant (cancer) cells form
in the tissues of a parathyroid gland.
 Having certain inherited disorders
can increase the risk of developing
parathyroid cancer.
 Signs and symptoms of parathyroid
cancer include weakness, feeling tired,
and a lump in the neck.
 2 - CALCITONIN
 Calcitonin is a peptide hormone made up of
32 amino acid residues that is secreted from
the para-follicular cells, also known as C
cells.
 CHEMISTRY & SYNTHESIS: Calcitonin is
a polypeptide chain with 32 amino acids. Its
molecular weight is about 3,400. It is
synthesized from pro-calcitonin.
 Mechanism of action

 Role of Cyclic AMP: Calcitonin binds

to specific calcitonin receptors on the
plasma membrane of bone-
osteoclasts and renal tubular
epithelial cells, activates adenyl
cyclase which increases c-AMP level
T which mediates the cellular effects
of the hormone. This is the principal
method by which calcitonin acts.
 Physiological functions
 1. On Blood Calcium Level :
Calcitonin plays an important role in controlling the blood calcium
level. It decreases the blood calcium level and thereby counteracts
Parathormone .Calcitonin reduces the blood calcium level by acting
on bones, kidneys and intestine.
i. On bones:
Calcitonin stimulates osteoblastic activity and facilitates the
deposition of calcium on bones. At the same time, it suppresses the
activity of osteoclasts and inhibits the resorption of calcium from
bones. It inhibits even the development of new osteoclasts in bones.
 Physiological Functions
ii. On kidney :
Calcitonin increases excretion of calcium through urine, by
inhibiting the reabsorption from the renal tubules.

iii. On intestine:
Calcitonin prevents the absorption of calcium from
intestine into the blood.
 2 – On Blood Phosphate Level
 With respect to calcium, calcitonin is an antagonist to PTH.
But it has similar actions of PTH, with respect to phosphate.
It decreases the blood level of phosphate by acting on bones
and kidneys.
i. On bones :
Calcitonin inhibits the resorption of phosphate from bone and
stimulates the deposition of phosphate on bones.
ii. On kidney :
Calcitonin increases the excretion of phosphate through
urine, by inhibiting the reabsorption from renal tubules.
 DISORDERS
 Disorders mostly caused by the hyper – secretion of
calcitonin :

 Medullary thyroid cancer (MTC):

 This is a rare thyroid cancer that originates in the C cells
of thyroid gland
 C CELL HYPERPLASIA :

This is a benign (non-cancerous)

condition that causes the abnormal
growth of C cells of thyroid .