Endocrinology

Dr. Chandra Shekar

Study of hormones secreted by specialized glands that are ductless is known as endocrinology.
Hormones are special chemical messengers present constantly in circulation. The organ/tissue
on which the hormone acts is known as target organ. The hormones carry chemical messages to
almost all the parts of the body and hence are important along with nervous system for regulation
of functions.


Apart from the hormones, certain other chemical signals are also secreted by cells. These are
termed as
a. Autocrines
b. aracrines
c. ! " tract hormones
Autocrines are chemical signals produced by the cell and influences the activity of the cell
itself. Autocrine effects are more important for growth and sustenance of cancer cells. "n a hostile
environment, normal cells can#t grow but the cancer cells grow and proliferate.

1
Paracrine are chemical signals produced by a cell and diffuses in the surrounding area
and act on the cells nearby. Somatostatin which regulates the secretion of insulin and glucagon
is e$ample for this.

! " tract hormones are not included under classical endocrinology. The hormones of ! " tract act
on the structures in ! " tract and alter the secretion and movements.
The hormonal functions in the body are:
%egulation of the metabolism
%egulation of water and electrolyte content
Help for growth
&ecessary for the reproduction
"n certain situations they help the body to withstand stressful stimuli.
The endocrine glands are present in different parts of body. 'ew of them are paired like adrenals
and the others are unpaired like pituitary.
". ypothalamus
!! Anterior " posterior pituitary
!!!. !slets of #angerhans
!$. Adrenal corte% " adrenal medulla
$. Thyroid
$!. Parathyroid
$!!. Testes&'varies
Essential endocrine glands:
(ean that )ithout the secretions of these glands the basic survival of the person is not
possible. The essential endocrine glands in the body are
arathyroid
Adrenals
Chemical nature
The biochemical nature of the hormone can be
eptide/ protein
Steroid
2
Amino acid derivatives
Peptide hormones can never be given orally as they get digested in the intestine.
(. Amino acid derivatives) Thyro$in, *atecholamine
+. rotein/ "nsulin
eptides) !lucagon
arathyroid hormone
ituitary hormones
,. Steroids) Hormones of adrenal corte$
Se$ steroids
Transport
Hormones are circulated in blood stream in two forms
'ree form
rotein bound form -with plasma proteins..
The amount of free form in circulation is very less but still is important as it e$erts all the biological
actions of the hormone. The protein bound form acts as reservoir and is released into free form
as and when re/uired. Apart from this, the protein bound form is not filtered in kidneys and hence
hormones loss from body is prevented.
Degradation of hormones
0ost of the hormones are metabolized in the target organs)
(. 1y the target tissue
+. 1y the 2iver/3idney 4 *on5ugated either by glucuronyl transferase system or by S6
7
Hormones belonging to steroid group are metabolized in the liver.
Tropic hormone
The hormones* )hich are essential for the regulation of gro)th and secretion of some
other endocrine glands* are kno)n as tropic hormones.
All the tropic hormones are secreted by the anterior pituitary gland. They are
TS +thyroid stimulating hormone,
ACT +adreno cortico tropic hormone,
-S +follicular stimulating hormone,
# +!CS, +leutini.ing hormone or interstitial cell stimulating hormone,
To certain e%tent even gro)th hormone also is considered as tropic hormone.
The tropic hormone secretion from anterior pituitary gland is under the influence of neuro
hormones secreted by the hypothalamus.
(echanism of action
Second 0essengers)
eptides and *atecholamine 4 'ormation of cyclic A0
4 *alcium
4 "nositol triphosphate -",.
4 8iacyl glycerol -8A!.
3
ormones in general act as first messenger.
roteins and peptide hormones can bind to the cell membrane receptors. Hence when they act
on the receptors, in the intra cellular fluid part there will be alteration in the concentration of
substances like cA0, *a
99
or inositol triphosphate. These substances act as second
messengers and e$ert all actions of the hormone in the intra cellular fluid region.
Steroid hormones can enter the cell through the cell membrane and bind to the receptors present
in the cytoplasm or the nucleus. This increases the formation of m%&A by a process known as
transcription and helps for synthesizing new proteins.
Thyro$in hormone binds to the receptors present on the nucleus.
/eceptors:

%eceptors for the hormonal actions can be present at , different places in the target organ/cells.
(. *ell membrane bound receptors are for all peptide hormones and catecholamine.
+. *ytosolic receptors for steroid hormone group.
,. &uclear receptors for thyro$in hormone.
/egulation of receptor number in the target organ depends on the concentration of the
hormone in circulation.
Do)n regulation is brought about when almost all the receptors are occupied by the hormone.
There will be almost no receptors available for binding with fresh molecules of the hormone. This
normally occurs in hypersecretory state of the hormone.
0p1regulation occurs when the hormone is not available for binding with the receptors. "n other
words, in this situation most of the receptors are free to bind with hormones. This normally occurs
in hyposecretory state of the hormone. :hatever little hormone is available, the receptors want to
bind with it.
/egulation of secretion of hormones:
2. -eedback mechanism: The a$is involved is hypothalamo anterior pituitary -hypophyseal. and
the gland concerned. "ncrease in the hormonal level in circulation will decrease the further
secretion of hormone acting either on hypothalamus or anterior pituitary or both. This is termed
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as negative feedback regulation. 'ne of the e%amples for this is regulation of secretion of
thyro%in hormone.
As opposed to the above, if the increase in hormonal level in circulation stimulates further
secretion of the hormone acting either on hypothalamus or anterior pituitary gland or both, this is
termed as positive feedback regulation. E%ample for this is regulation of secretion of
estrogen hormone around the day of ovulation.
Cause for imbalance in hormonal secretion can be due to problem any )here in the a%is.
-or e%ample* if the problem
is with the gland concerned, it is termed as primary
is due to anterior pituitary gland, it is termed secondary
is at hypothalamus, it is termed tertiary
3. Substrate influence: :hen concentration of certain substance is altered in circulation, the
substance can directly influence the glandular activity to either increase or decrease the amount
of hormone secreted. -or e%ample* increase in blood glucose level in circulation* directly
acts on beta cells of islets of #angerhans and increases the amount of insulin secretion.
4. 5eural influences: The activity of the nervous system can also regulate the secretion of some
hormones. E.g. *atecholamine, and prolactin secretion is regulated by neural activity. The neuro4
endocrine refle$ can also be included here -for details refer to o$ytocin secretion regulation..
6. Stressor influences: *an also alter the secretion of hormones. Any sort of stress either alters
the internal environment or threaten to alter the homeostasis. *ommon e$amples of stress
include a. somatic like accidents, burns etc., b. mental like death of near and dear ones, certain
apprehensions etc. "f this stressful situation is not combated, it may become fatal. "n such a
situation hormonal secretion is altered, e.g. increased secretion of cortisol in any stress
situations.
7. Diurnal variation: 8uring +7 hours of the day, the rate of hormone secretion varies depending
on the time. E.g. Secretion of A8H is more during the night than during day time. ;ven cortisol
secretion has diurnal variation and is more during day time when compared to night time.
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alf life of hormone: is the time re/uired for the hormone level to fall to <=> of its original level.
The half life varies with the hormones. *atecholamine has very less half life of about += secs
whereas thyro$in has half life of about ? days. The half life of hormone will also depend on
whether the hormone is present in free form only or both in free form and protein bound form. "n
case hormone is present only in free form the duration of half life is very less -e.g.
catecholamine..
Anterior pituitary gland
"s also known as adenohypophysis.
Secretes a number of hormones which are generally termed as tropic hormones.
The secretion of hormones from anterior pituitary is regulated by factors secreted by the
hypothalamus. The hypothalamic factors are of two types namely
a. %eleasing factors or releasing hormones.
b. %eleasing inhibiting factors or release inhibiting hormones.

8/ @ !rowth hormone releasing hormone SS @ Somatostatin
T/ @ Thyrotropin releasing hormone DA 4 8opamine
8n/ @ !onado tropic releasing hormone, C/ @ *ortico tropin releasing
hormone
8 @ !rowth hormone TS @ Thyroid stimulating hormone
P/# @ rolactin # @ 2uteinizing hormone
-S @ 'ollicular stimulating hormone ACT @ Adreno cortico tropic hormone
9 #P 4 A 2ipotropin 9 E5D'/ 4 A ;ndorphin
The anterior pituitary is connected to the hypothalamus by hypothalamo hypophyseal
portal system. The factors secreted by the hypothalamus reach anterior pituitary gland
through this vascular connection.
6

Diagram sho)ing connection bet)een hypothalamus and anterior pituitary gland
+vascular connection : hypothalamo hypophyseal portal system,
The cells of anterior pituitary are grouped into two types namely the chromophobes and
chromophils. The chromophils are further divided into acidophils and basophils.
*hromophils are cells which secrete the factors of the hypothalamus which in turn
influence the activity of the anterior pituitary gland.
The chromophil cells of anterior pituitary are named based on the hormone they secrete.
;$amples are)
a. Somatotropes which secrete growth hormone.
b. #actotropes which secrete prolactin.
c. Thyrotropes which secrete thyroid stimulating hormone.
d. 8onadotropes which secrete follicular stimulating and leutinizing hormones.
e. Corticotropes which secrete adreno cortico tropic hormone, beta lipotropins and beta
endorphins.
8ro)th hormone
!rowth hormone -!H., also known as somatotropic hormone and is a peptide hormone secreted
by acidophils of the anterior pituitary gland. !H is stored in large, dense granules present in
acidophil cells. "t is a single chain polypeptide with molecular weight of ++,=== having (B( amino
acids and two disulphide bridges. As the name indicates, its action is on the lean body mass. "t
stimulates somatic growth and development and helps to maintain lean body mass and bone
mass in adults.
(echanism of action:
%eceptors for growth hormone are present on the plasma membrane of cells.
1elong to cytokine family of receptors.
resence of e$cess of !H down regulates the synthesis of its receptors.
0any hours must elapse after administration of !H before anabolic and growth promoting
actions of the hormones to become evident.
0ost of the actions of !H re/uire the production of !H induced somatomedin * or insulin
like growth factor -"!'..
The plasma half life of "!' is much longer than that of !H.
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Actions of hormone can be broadly classified into two types)
a. "ndirect growth promoting action
b. 8irect anti insulin action.
2. !ndirect gro)th promoting action is due to the action of growth hormone on liver. :hen
hormone acts on liver, liver secretes somatomedin C or insulin like gro)th factor +!8-1!,.
This substance acts on skeletal and e$tra skeletal compartment.
Skeletal compartment: :hen somatomedin acts on epiphyseal plate present
between long bones, the epiphyseal plate is widened. This gives space for the
chondrogenesis of the long bones. The long bones grow linearly. Hence the height
of the person increases. The long bones can grow only up to the age of about (C4+=
years beyond which epiphyseal plates get fused with long bones and there can be
no more linear growth of body.
E%tra skeletal compartment: This in general refers to the growth of organ and
tissues. The growth is brought about by hyperplasia -stimulating mitotic cell division
and hence increase in cell number. and hypertrophy -increase cell size.. The
various tissues in the body grow. There will be increased protein synthesis because
of which it brings about positive nitrogen balance. The proteins synthesized are
incorporated for the growth of the organs.
The various parts of the body do not grow in proportion at the same time. The growth of the
different parts of the body based on chronological age has been shown in the following
diagram.

3. Direct anti1insulin action: This can be brought about in the target organs in presence of
cortisol -permissive action of cortisol is re/uired..
'n carbohydrate metabolism: "t is a hyperglycemic agent. "ncreases the blood glucose
level by
a. 8ecreasing the peripheral utilization of glucose.
b. "ncreased gluconeogenesis in liver.
(etahypophyseal diabetes: Dncontrolled secretion of !H for a long time brings about increase
in blood glucose level. This leads to increase stimulation of beta cells of islets of 2angerhans to
secrete insulin. After sometime due to constant stimulation, the beta cells get e$hausted and lead
to development of diabetes mellitus.
-at metabolism: Acts on the adipose tissue. &eutral fats and triglycerides are broken down to
release free fatty acids. They are utilized for energy supply to tissues. This can lead to increased
production of keto acids.
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!rowth hormone also promotes the retention of sodium, potassium, calcium and phosphate since
these substances are re/uired for the growth of the body.

/egulation of secretion is mainly by the negative feedback control by the free form of the
hormone level in circulation.

!rowth hormone releasing hormone -!%H. secreted from hypothalamus acts on anterior pituitary
gland and stimulates secretion of growth hormone, which in turn increases insulin like growth
factor -"!'. secretion from liver. :hen "!' level in circulation increases, it acts on hypothalamus
to stimulate secretion of somatostatin -SS.. SS on reaching anterior pituitary decreases secretion
of growth hormone.
"!' also acts directly on anterior pituitary and e$erts inhibitory influence on secretion of growth
hormone.
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Some of the other factors that increase the secretion of gro)th hormone are:
"ncrease in amino acids in circulation
Hypoglycemia
'ree fatty acid decrease
;$ercise
At puberty
Stage "E sleep.
The factors )hich inhibit the 8 secretion are:
8reaming or rapid eye movement
-%;0. sleep.
!lucose increase.
*ortisol.
6besity.
Applied aspects:
D)arfism:
"s because of hyposecretion of !H from childhood.
erson will have short stature. There will be stunted growth of the body.
The person will have normal reproductive development.
There will not be any mental abnormality and will have normal intelligent /uotient -"F..
'acial changes correspond with chronological age.
Achondroplasia is the most common form of dwarfism. The characteristic feature will be short
limbs and normal trunk.
#aron d)arf)
:ill be due to insensitivity of the tissues to !H.
The receptors are non responsive to !H.
There can be normal or elevated level of !H in circulation.
Progeria: 8eficiency of growth hormone in adult. The person appears older at young age.
Acromegaly:
Hyper secretion of growth hormone after the puberty.
;nlargement of hand and feet -acral parts of the body only can grow because of
ossification of long bones..
There will also be enlargement of mandible which results in prognatism. There will also
be enlargement and protrusion of frontal bone. 1ecause of this, person may have gorilla
like appearance.
*ertain osteo4arthritic changes are also observed leading to kyphosis.
There can be enlargement of viscera especially that of heart and may lead to
cardiomegaly.
There can be hirsutism -increased hair growth on anterior part of trunk. and
gynaecomastia -enlargement of breasts. and lactation -secretion of milk..
The person may suffer from bitemporal hemianopia -type of visual field defect. due to
compressing on the medial part of optic chiasma by enlarged pituitary gland.
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8igantism:
Hypersecretion of hormone from childhood.
Size of person is pathologically big, but the person will be weak. Hence the person is
known as weak giant. There will not be proportionate growth of contractile proteins in the
muscles. Hence muscles are weak.
The person is prone to develop early diabetes. This is because since growth hormone
has hyperglycemic action, sustained increase in blood glucose level may lead to
e$haustion of beta cells of islets of 2angerhans. So person develops diabetes.
The longevity of these people is restricted and dies early.
Sheehan;s syndrome)
6ccurs in female. 8ue to post4partum hemorrhage, there can be ischemic necrosis of
pituitary gland.
ituitary gland secretion in general is decreased.
Symptoms include lethargy, se$ually inactive, unable to withstand stress. !rowth is
inhibited and thyroid function is depressed.
There can be atrophy of gonads. The menstrual cycle stops.
:hen there is general deficiency of all the hormones of anterior pituitary gland, this
condition is known as panhypopituitarism.
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Posterior pituitary hormones
The hormones of posterior pituitary gland are synthesi.ed in neurons of hypothalamus.
The two different groups of neurons in hypothalamus, which synthesize these hormones are,
supra optic and para ventricular nuclei -they are also known as magno cellular neurons in
general..
The hormones are transported from the hypothalamus to the posterior pituitary gland through
a$oplasmic flow. Supra optic and para ventricular nuclei of the hypothalamus are connected to
posterior pituitary gland through hypothalamo hypophyseal tract. :hen impulses come through
this tract to posterior pituitary gland, hormones stored in the gland are released into circulation.
Supra optic nucleus predominantly secretes anti diuretic hormone -A8H /vasopressin. and para
ventricular nucleus predominantly secretes o$ytocin hormone. 1oth are peptide hormones.

Actions of Anti diuretic hormone
As the name indicates the hormone decreases volume of water lost in urine and thereby helps to
maintain body water content by conservation of water. The sites of action are kidney and smooth
muscle of blood vessels:
2. <ater reabsorption
!t acts on the epithelial cells lining the collecting duct and also distal convoluted
tubule through $
3
receptors.
This brings about the insertion of )ater channels +a=uaporins, in epithelial cells.
Through these channels )ater gets reabsorbed.
(ost the )ater reabsorbed in these regions of the kidney is under the influence of
this hormone.
3. 0rea movement
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'acilitates rate of urea recycled from the collecting duct. The reabsorption of water from 8*T and
*8 increases concentration of urea in fluid present in tubular lumen. 8ue to the concentration
gradient between tubular lumen and interstitium in renal medulla, urea diffuses into interstitium.
'rom the interstitial region of renal medulla along the concentration gradient urea diffuses back
into fluid present in ascending limb of loop of Henle.
4. /ate of blood flo) through vasa recta
"t reduces the rate of blood flow through the vasa recta and increases time available for operation
of counter current system. 8ecreased rate of blood flow through vasa recta is essential for
concentration of urine.
All three aforesaid actions help in concentration of urine.
6. $ascular smooth muscle
"n addition to the above actions, A8H in large doses acts on smooth muscle of blood vessels
through the E
(
receptors and brings about vasoconstriction. 1ecause of this, there will be
increase in peripheral resistance and hence increase in diastolic blood pressure.
/egulation of secretion
%egulation of secretion is brought about by two important mechanisms. There is involvement of
osmoreceptors and volume receptors in regulation of secretion.
2. 'smoreceptors:
They are present in the hypothalamus near the supra optic nucleus. :hen plasma osmolality
increases -normal is ,== m6sm/2 water., water moves out of osmoreceptors into interstitium by
e$osmosis. This leads to shrinkage of the osmoreceptors and conse/uent stimulation of them.
This in turn stimulates supra optic nucleus. 'rom the supra optic nucleus more impulses are sent
to posterior pituitary through the hypothalamo hypophyseal tract. 1ecause of this more anti
diuretic hormone will be released into circulation. This helps for increased retention of water
through kidneys and normalizes osmolality of the plasma.
3. $olume receptors:
Eolume receptors are present in walls of the great veins and on right side of heart. These
receptors are also known as low4pressure receptors. "ncrease in blood volume, stretches the
walls of great veins and right side of heart and stimulates these receptors. Afferent impulses from
the receptors reach hypothalamus and inhibit the activity of supra optic nucleus. This decreases
fre/uency of impulses along hypothalamo hypophyseal tract to posterior pituitary gland. So less
amount of anti diuretic hormone is released from the posterior pituitary gland into circulation. This
decreases the volume of water reabsorbed from renal tubules. "ncreased urine output will restore
blood volume.
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Some of the other factors that can alter secretion of the hormone are:
Alcohol
ain
Surgery
Trauma.
Applied aspect
Diabetes insipidus) 6ccurs due to deficiency of anti diuretic hormone secretion.
:hen condition is due to decreased secretion of A8H* it is termed as 5eurogenic diabetes
insipidus.
As opposed to the above* in 5ephrogenic diabetes insipidus, secretion of A8H is normal.
%eceptors present on cells of renal tubules fail to respond for A8H.
Some of the features of diabetes insipidus are:
Polyuria: "ncreased volume of urine e$cretion due to loss of concentrating ability in
kidney.
Polydypsia) "ncreased thirst center activity due to decrease in body water content.
erson drinks more water.
!lucose will be absent in urine and blood glucose level will be normal.
Specific gravity of the urine will be less due to e$cretion of more dilute urine most of the
times.
Actions of o%ytocin
'n the breasts
Acts on myoepithelial cells of the breasts. This causes e5ection of milk from alveolar ducts
of the breasts.
'n myometrium
Acts on myometrium of uterus and causes severe contraction of myometrium. This leads
to parturition or delivery of fetus due to an increase in intra uterine pressure.
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"n non4pregnant woman, o$ytocin is believed to bring about minute myometrial
contractions which facilitate movement of sperm along uterus to reach fallopian tubes.
"n males, it is believed to bring about contraction of smooth muscles in vas deferens and
facilitate sperm movement in genital system.
/egulation of secretion
/egulation of secretion is brought about by a neuro endocrine refle%. "n this refle$, part of
refle$ pathway is neural and part is hormonal. 0ilk e5ection and parturition refle$es are classical
e$amples of neuro endocrine refle$.
2. Suckling of the breasts brings about the stimulation of the touch receptors present on
the nipple and areola.
3. <hen head of the fetus presses on the cervi%* the stretch receptors present in the )alls
of cervi% are stimulated.
'rom the above two receptors, impulses sent along ascending tracts of spinal cord to
hypothalamus to stimulate araventricular nucleus. 0ore amount of o$ytocin is secreted to bring
about desired actions.
THYROID GLAND
The hormones secreted by this gland are
Thyro$in -T
7
.
Triiodothyronin -T
,
.
Thyrocalcitonin -*alcitonin.
Among the three hormones, follicular cells of the gland secrete first two hormones -T
,
G T
7
. and
the last one -thyrocalcitonin. is by parafollicular cells. T
7
is also known as tetraiodothyronin and
gets converted to T
,
at the time of action in target organ. *alcitonin hormone will be discussed
along with calcium metabolism.

1iosynthesis of hormone is regulated by activity of TSH secreted from anterior pituitary gland.
Since it is a tropic hormone, TSH regulates the growth and functioning of thyroid gland.
The following diagram indicates the action of TSH on thyroid gland.
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The steps in the biosynthesis of the hormone are
!odide trapping that is uptake of iodide by follicular cells from the plasma against
electrochemical gradient. The hormone TSH secreted by anterior pituitary gland affects
this step. Substances like thiocyanate, pertechnetate and perchlorate that are
e$amples of antithyroid drugs can inhibit iodide trapping.
'%idation of iodine: 6ccurs inside follicular cells by action of enzyme pero$idase.
8rugs like thiouracil and carbimazole can inhibit this step and act as antithyroid drugs.
'rganification: "odine gets incorporated to tyrosine amino acid present in colloid and
leads to formation of 0"T -0ono iodo tyrosine.. 6n further iodination of 0"T, there is
formation of 8"T -8i iodo tyrosine..
Coupling: *oupling of + 8"T will lead to formation of T
7
and ( 0"T with ( 8"T will
results in T
,
.



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At the time of release of the hormones into circulation, acinar cells will engulf thyroglobulin along
with hormones by endocytosis.
"n the cells hormone will be separated by proteolysis and released into circulation and
thyroglobulin will be retained for further use.
0ost of the hormone in circulation is in protein bound form along with thyroid binding globulin
-T1!., albumin -T1A., thyroid binding pre4 albumin -T1A..
Actions of the hormone
2. Calorigenic action
"ncreases o$ygen consumption in almost all tissues of body e$cept adult brain,
gonads, lymphoid tissue etc. "ncreased metabolic rate increases heat production in
body. The unit to measure heat energy is calorie.
"n normal adult male basal metabolic rate -10%. is about 7= 3cal/s/ m 1SA/Hr H
(<>.
"n hyperthyroidism it can be as much as 9 I= to (== >.
"n hypothyroidism it can fall by 4 7= to I= >.
Hence estimation of 10% forms one of the thyroid function tests.

3. 5ervous system
'or growth of the nervous system in the first , years of the postnatal period the action of
the thyro$in on brain is essential. The growth of the brain occurs only during this phase.
The gro)th of the brain includes
'ormation of synapses
!rowth of a$on and dendrites and arborisation of these processes
"ncrease in number of glial cells
(yelination of nerve fibers
!n cretin:
(. The brain remains smaller than normal.
+. &umber and size of nerve cells reduced.
,. Arborization of dendrites is less profuse
4. &et effect in child will be marked decrease in ".F
<. 0yelination will be defective
I. *S' 4 rotein content increased
>ecause of these reasons the action of hormone on the brain is very crucial in first one to
t)o years of postnatal life. !f there is deficiency of hormone during this period it can lead
to mental retardation. This is associated )ith delayed milestones during gro)th of infant.
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4. 'n gro)th and development
"t affects the growth and development of other parts of body as well.
The general growth is influenced by growth hormone of anterior pituitary gland
but thyro$in potentiates action of growth hormone and hence the summated
effect of these hormones is very much for linear growth of body and growth of
other organs.
"t also affects the growth of reproductive organs and lack of the hormone may
lead to sterility, infantile se$ organs in adults and in adult females menstrual
problems.
6. (etabolic actions) Apart from its action on o$ygen consumption by tissues, it also
influences metabolism of carbohydrate, fats and proteins.
a. Carbohydrate metabolism: acts as hyperglycemic agent.
"ncreases blood glucose level by increasing gluconeogenesis and glycogenolysis in
liver.
"t also enhances peripheral utilization of glucose.
b. Protein metabolism: Has both anabolic and catabolic effects. ;$cess of hormonal level
in circulation, catabolism predominates and leads to loss of body weight and muscular
weakness. "n hypothyroidism anabolism suffers and again leads to muscular weakness.
c. -at metabolism: "ncreases lipolysis. *holesterol synthesis and degradation are both
affected by this hormone. The degradation is more dependent on thyro$in than synthesis
and hence in hypothyroidism serum cholesterol level is increased.
d. 'n mucopolysachharides: E$cretion of substances like hyaluronic acid and chondroitin
sulphate is affected by action of this hormone. Hence in hypothyroidism they get
deposited in the sub4cutaneous region giving rise to my$oedema
7. 'n systems: The hormone affects functioning of different systems of body. Some of
systems on which the actions are more pronounced are
a. C$S
"t increases both heart rate and force of contraction.
"t increases number of beta receptors and affinity of the beta4receptors for
catecholamine.
Hence resting heart rate will be more in hyperthyroid sub5ects. The increase in
cardiac output leads to increase of systolic blood pressure -systolic hypertension..
"t also increases blood flow to the skin in order to facilitate heat loss from the body.
"t is essential as the hormone increases basal metabolic rate and hence increased
heat production. As a result of this cutaneous vasodilatation, peripheral resistance
decreases which will result in fall in diastolic 1.
b. 8!T: Hormone is re/uired for normal secretory aspects and movements of gastro
intestinal tract. "n hyperthyroidism patients suffer from diarrhoea and in hypothyroidism it
is constipation.
c. 5ervous system
"n adult it affects the velocity of impulse conduction in nerve fibers. "n hyposecretion state it
results in increased refle$ time and vice versa in hyperthyroidism.
/egulation of secretion of hormone: is brought about by the negative feed back
mechanism. There is involvement of hypothalamo 1 pituitary ? thyroid a%is
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Alteration in the temperature can directly act on the hypothalamus to alter the secretion of
the hormone.
Thyroid function tests:
(. 8etermination of 10%.
+. 1lood cholesterol level.
,. ;stimation of protein bound iron -1".
7. "
(,(
uptake studies
<. ;stimation of free T,, T7 and TSH in plasma.
Thyroid function tests: Test /adio active !odine 242 studies

Applied aspects:
Cretinism:
Hyposecretion of thyro$in from infancy.
Skeletal growth will be stunted and hence short stature.
0ental retardation due to poor growth of nervous system.
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0ilestones in development of child get postponed.
Thick protruding tongue and pot belly.
;ven after attaining adolescence, there will not be development of se$ organs and hence
se$ organs remain infantile.
'acial changes will not correspond with chronological age.


(y%oedema)
Hyposecretion of thyro$in in adults.
erson#s basal metabolic rate is grossly reduced. "t can be as little as minus 7= to I=>.
erson can#t withstand cold stress.
*old dry skin with sparse hair. There will be accumulation of chondroitin sulphate and
hyaluronic acid in sub4cutaneous region. These substances are osmotically active and
hence results in retention of water also in sub4cutaneous region. This results in non4
pitting edema -puffiness of face, legs etc..
erson will have bradycardia and blood pressure also will be less than normal.
The activity of *&S becomes dull thereby it may lead to loss of memory and dulling of
intelligence and reaction time is prolonged.
There will be increase in serum cholesterol level.
The reproductive ability of person suffers and females may suffer menorrhagia.
20

8rave;s disease:
Hyperthyroidism in adult stage.
erson may show e$ophthalmos.
Tachycardia and palpitation.
erson may suffer from systolic hypertension.
&egative nitrogen balance with loss of wasting of muscle tissue.
*&S symptoms include tremors, hyper4refle$ia, and psychosis.
1asal metabolic rate may be increased to as much as plus 7= to I=>.
erson can#t withstand heat stress.
Skin will be warm and wet.
Serum cholesterol level will be less than normal.
erson may suffer from loss of libido and infertility.

The disease may be because of autoimmunity. The body starts producing antibodies which are
known as thyroid stimulating immunoglobulins -TS". or long acting thyroid stimulators -2ATS..
These antibodies bind to receptors where TSH normally binds. They imitate action of TSH on
21
gland and hence bring about increased secretion of thyro$in. Since the thyro$in level in circulation
is increased, this e$erts more negative feedback regulation on anterior pituitary. So TSH
secretion from anterior pituitary gland is decreased. This results in decreased concentration of
TSH in circulation.
8oiter means enlargement of thyoriod gland. !oiter can be due to hypo or hyper thyroidism.
;ndemic goiter -hypothyoroidism. usually occurs due to deficiency of iodine. ;$ophthalmic goiter
occurs due to hyperthyroidism.

Endocrine function of Adrenal Corte%
The adrenals are made up of two parts. 6uter zone known as adrenal corte$ -an essential
endocrine gland region. and inner core region is adrenal medulla. The hormones secreted by
adrenal corte$ are collectively known as cortico4steroids whereas medullary hormones are known
as catecholamines. Apart from this difference, even during embryonic life they get developed
from entirely different regions and medullary region is nothing but the modified ganglion of the
sympathetic nervous system.
Adrenal corte%
!s divisible into 4 different layers* from out)ards )ithin )ill be
Jona glomerulosa
Jona fasciculata
Jona reticularis.
All three layers secrete the hormones.
Jona glomerulosa secretes mineralocorticoids of which the most important is aldosterone.
Jona fasciculata and reticularis together secrete glucocorticoids of which the most important is
cortisol G corticosterone. The layers also secrete se$ steroids, of which adrenal androgen is most
important. 1oth glucocorticoids and mineralocorticoids can e$ert the action of the other group as
well, when concentration of hormone is very high.
22

1iosynthesis of hormones)

23

!enetic defects in cortisol biosynthesis have important conse/uences. A defect in +( or ((4
hydro$ylase enzyme gene leads to over production of androgenic steroids from precursors.
Hence there will be production of e$cess of androgens and this causes masculinization of female
fetuses# in utero and early secondary se$ual changes in male infants and young boys.
Cortisol is transported in circulation. A ma5or part of it is in protein bound form along with globulin
-cortisol binding globulin @*1!.. The level of this protein increases in pregnancy because of
which in initial stages, free form of hormonal level in circulation decrease. This in turn stimulates
more secretion of hormone by increased secretion of A*TH from anterior pituitary gland. 2evels
of *1! decrease in cirrhosis of liver and in nephrosis.
Actions:
Permissive action: *ortisol should be present in target organs for action of certain other
hormones. 'or e.g. the catecholamine can e$ert vasoconstrictor effect on vascular
smooth muscle only in presence of cortisol. The vasoconstrictor effect is necessary to
maintain peripheral resistance and hence blood pressure. ermissive action of cortisol is
also re/uired for certain actions of growth hormone and glucagon.
(etabolic actions
a. Carbohydrate metabolism: "t is a hyperglycemic agent G increases blood glucose level
1y decreasing peripheral utilization of glucose in almost all parts of body e$cept heart
and brain
1y increasing gluconeogenesis and glycogenesis in liver.
;$cessive use of cortisol as therapeutic agent may lead to e$haustion of beta cells of pancreas
and cause metasteroid diabetes.
b. Protein metabolism: "n large doses it enhances protein break down especially in lymphoid
tissue, muscles, and bones, leading to)
8ecreased immunity
0uscular weakness
:eight loss
Susceptibility of bones for fracture.
24
Amino acids released due to protein break down are used for gluconeogenesis in liver.

c. -at metabolism: The hormone generally increases lipolysis in adipose tissue. So brings
about the break down of neutral fats and triglycerides. This will result in increase in free fatty
acids and glycerol in circulation.
'ree fatty acids are used both for energy supply to tissues and
!luconeogenesis in liver.
There will be redistribution of fats in body.
'ats are removed from peripheral parts and deposited in more central parts of body
resulting in moon face, buffalo hump G pendulous abdomen.
d. (ineral metabolism: ;$cess of cortisol can also e$ert some amount of aldosterone like
action. Hence it increases sodium reabsorption in distal convoluted tubule and in e$change
for this potassium e$cretion in urine increases. %eabsorption of sodium increases water
retention, so blood volume and blood pressure are increased.
e. <ater metabolism: erson with low levels of cortisol has defective water regulation in the
body may be because increase in the plasma anti diuretic hormone level and decreased
glomerular filtration rate. 1oth of these contribute for delayed water e$cretion. The retention
of water by body can lead to water into$ication.
'n organs
(. C5S: "ncreases the activity of the neurons in central nervous system and hence patient may
have euphoria. "t will also increase irritation of neurons and because of which, administration
of this as drug to any patient susceptible to/suffering from epilepsy should be borne
in mind. Administration of this drug may worsen the condition.
+. 8!T: In large dose increases gastric acid secretion and damages mucus barrier. So
people are more prone to develop peptic ulcer.
25
,. Skeletal muscle) ;$cess of cortisol leads to muscular weakness promoting protein
catabolism and insufficiency also causes muscular weakness.
7. >lood: *ortisol insufficiency leads to eosinophilia, lymphocytosis etc whereas e$cess of
cortisol brings about eosinopenia, lymphocytopenia. ;osinophil count is decreased because
of se/uestration of cells in liver.
<. >one) e$cess of cortisol impedes development of cartilage and causes thinning of
epiphyseal plates. There will also be defective synthesis protein matri$ and deposition of
calcium salts. 1ecause of these things, osteoporosis occurs in *ushing#s syndrome.
Pharmacological actions occur only when levels are far in e$cess.
Anti1inflammatory action: "n some people acute inflammation can cause more damage to
tissues. "nflammation is due to increased
a. 1lood flow due to increased metabolic rate of the bacteria at the site of infections
b. ermeability of the capillaries
c. ;migration of leucocytes to site of infection from blood vessels
d. 2ysozyme release from cells leading to proteolysis.
Cortisol counters the aforesaid effects by decreasing
a. 0etabolic rate of bacteria
b. *apillary permeability
c. ;migration of leucocytes and stabilizing the lysozymes.
Cortisol should never be administered alone in bacterial infection as anti1inflammatory
agent. !t should al)ays be combined )ith antibiotics to take care of bacteria@ other)ise it
can lead to spread of bacteria* )ithout overt reaction of body to infection. This can lead to
serious problems.
Anti allergic activity
;specially in organ or tissue transplantation sometimes recipient#s body resists or re5ects the new
organ/tissue. *ortisol can be used to bring about immuno suppression reactions. This helps to
prevent re5ection of transplanted tissues.
Suppresses immune responses by
8ecreasing eosinophil, and lymphocyte count.
8ecreasing eosinophil count by se/uestration of cells in liver and spleen.
8ecreasing lymphocyte percentage by catabolism of proteins in lymphoid tissue. Hence
it will decrease concentration of circulating antibodies in course of time.
/egulation of secretion
1y negative feed back mechanism and there is involvement of hypothalamo4pituitary4adrenal
a$is. "ncrease free form of hormone in circulation acts on hypothalamus and anterior pituitary
gland. 'rom hypothalamus secretion of corticotrophin releasing factor -*%'. decreases, so it
leads to decreased secretion of A*TH. *ortisol also acts directly on anterior pituitary gland and
inhibits secretion of A*TH. 8ecreased A*TH leads to less of cortisol secretion from adrenal
gland. Apart from this, stress and circadian rhythm directly act on hypothalamus to alter
secretions.
26



Aminoglutethimide is potent inhibitor of desmolase reaction and thereby decreases all steroid
hormone synthesis. This drug has been used to treat women with breast cancer. 3etoconazole
an antifungal agent also inhibits several steps in biosynthesis of the hormones and thus effective
in treating states of e$cess of cortisol secretion.
Adrenal androgens
Dihydro epiandrosteinodione +DEA, and androstenedione are )eak androgens. "n
peripheral tissues they are converted to potent androgen, testosterone.
"n female the actions of adrenal androgens are
Sustaining of normal pubic and a$illary hair.
27
"n menopausal stage, oestradiol of adrenal origin is important source of oestrogen
activity.
"n normal male amount of testosterone secreted by the testis far e$ceeds adrenal androgens and
not much role to play by the adrenal androgens. "f adrenal androgens secretion becomes
abnormally high especially in children, it can lead to precocious puberty.
Aldosterone
As stated already the most important mineralocorticoid is aldosterone, which is secreted by zona
glomerulosa.
Actions:
'n the kidney
Acts on distal convoluted tubule and increases sodium reabsorption. "n e$change for this, there
will be increased secretion of either potassium or hydrogen ion. Sodium reabsorption will be
coupled with chloride and water reabsorption as well. This will increase e$tra cellular fluid volume
and hence blood volume.
a. 6n epithelial cells of kidney when aldosterone acts, it facilitates the &a
9
K 3
9
pumps
activity at basolateral surface and increases reabsorption of sodium.
/egulation of secretion:


a. *oncentration of 3
9
and &a
9
in circulation can act directly on gland to alter secretion. 6f the
two, most potent is increase in concentration of potassium. The normal plasma 3
9
level is low -<
m;//2 water. when compared to &a
9
-(<= m;//2 water.. So, small alteration in 3
9
level will have
a profound effect on rate of secretion.
b. Angiotensin "") This is formed due to activity of renin4angiotensin system can directly act on the
adrenals and enhance secretion of hormone.
c. Some of other factors which can increase secretion of aldosterone are an$iety, physical trauma
and hemorrhage.
28



29
Conn;s syndrome:
*onn#s syndrome is due to primary hyperaldosteronism. Secondary hyperaldosteronism can be
due to liver disease, stenosis of renal artery etc. :hether hyperaldosteronism is due to primary or
secondary cause, there will be abnormal increase in secretion of aldosterone.
'eatures of *onn#s syndrome are)
Hypertension.
"ncreased total body sodium.
8ecreased plasma potassium.
Drine acidic
The person will suffer from alkalosis.
0uscle weakness, fatigue and
paralysis.
At times person may develop tetany.
olyuria
&o edema because of sodium
escape phenomenon.
Endocrine function of Adrenal (edulla
Secrete the hormones of emergency. The secretion is stimulated in conditions like fight, flight or
fright. 'or synthesis of hormone amino acid re/uired is phenylalanine. *atecholamine group
includes hormones adrenaline, noradrenalin and dopamine. "n human beings about C=> of
hormone secreted from this region is adrenaline.
>iosynthesis of hormones: Degradation of hormones:


0ost of hormone will be degraded in target organs and end products of metabolism are e$creted
along with urine in the form of vanilyl mandelic acid and as con5ugates.
Hormone acts through adrenergic receptor. The types of receptors are alpha and beta. They are
further divided into alpha ( and alpha + and beta ( and beta +. The action of the hormone on
target organ depends on type of receptor through which action is mediated.
30
Actions:
'n vascular smooth muscle: "n presence of cortisol it is able to act on the smooth muscle of
blood vessels especially in arteriolar regions. 8ue to this some amount of vasoconstriction is
maintained all time and hence peripheral resistance. eripheral resistance is the factor that is
responsible for the diastolic blood pressure. &oradrenalin is a powerful vasoconstrictor.
'n heart and blood vessels: "s able to increase both the heart rate and force of
contraction. This action is mediated through the beta receptors present in cardiac
muscle. "t e$erts both chronotropic and inotropic actions. Hence it increases
cardiac output and systolic blood pressure in general.
'n the blood vessels:

5oradrenalin:
Alpha receptors are present on smooth muscle of arterioles and when it e$erts its influence there
is will be vasoconstriction. &oradrenalin predominantly acts through this group of receptors and
hence there is an increase of total peripheral resistance in body. This is going to increase
diastolic blood pressure and hence there will be a secondary increase of systolic pressure as
well. "ncrease in diastolic 1 increases mean arterial pressure. The increase in blood pressure
will stimulate baroreceptors and hence there will be refle$ bradycardia and fall of cardiac output
after sometime.

'n >rain: "ncreases activity of the neurons of central nervous system and person becomes more
alert. 1ut if the amount acting on the brain is very much it brings about inhibition of spinal
refle$es.
'n bronchial smooth muscle: 1rings about the bronco dilation and relieves person suffering
from bronchial asthma.
'n skeletal muscle) increases blood flow and help to sustain the increase in muscular activity.
'n iris: Acts on dilator pupillae muscle and hence there will be dilation of pupil.
(etabolic effects: Acts as hyperglycemic agent and increase blood glucose level by stimulating
glycogenolysis in liver and muscle and gluconeogenesis in liver.
"t also increases the lipolysis and increases free fatty acid release and also the metabolic rate of
tissue. Since it enhances rate of metabolism it is termed as calorigenic agent. This increases
metabolic rate in body and hence there will be increased heat production. 1ecause of this, they
have important role to play when person needs immediate heat production when e$posed to cold
situations. There will also be more amount of blood flow to cutaneous region to facilitate increase
in heat loss.
8!T: Stimulates activity of sphincters and rela$es smooth muscle due to which there will be
decreased motility of !"T.
/egulation of secretion:
Adrenal medulla has efferent nerve supply from sympathetic nervous system
only. Any situation which leads to fight or flight situation, will increase
sympathetic activity and hence increased secretion from adrenal medulla
Phaeochromocytoma:
"s because of tumor in adrenal medulla.
There will be an abnormally high amount of secretion of hormones from adrenal
medullary region.
31
Some of the features of this condition are)
Sustained severe
hypertension.
alpitation.
Headache.
Sweating.
Hyperpnoea.
&ausea and vomiting.
An$iety and muscular
weakness.
Endocrine pancreas
ancreas is uni/ue gland having both e$ocrine and endocrine functions. The e$ocrine function is
contributed by the acini present in pancreas.
;ndocrine function of pancreas is performed by islets of 2angerhans, which is spread out
throughout pancreas and more concentrated in tail. There is appro$imately ( to + million islets.
The islets are made up of different types of cells which can be mode out by 0allory stain and they
are
(. Alpha cells or A cells which secrete glucagon
+. 1eta cells or 1 cells which secrete insulin
,. 8elta cells or 8 cells which secrete somatostatin
7. ' cells which secrete pancreatic polypeptide
:hen pancreatectomy was done on dogs by Eon 0ering and 0inkowski and later on by 1anting
and 1est, following features were observed in animals)
(. Hyperglycemia followed by glycosuria.
+. olyuria, polydypsia and polyphagia.
,. 2oss of body weight, early fatigue, weakness and poor growth,
7. 8elayed wound healing and repeated infections and negative nitrogen balance.
<. "ncreased lipolysis and decreased lipogenesis
I. 'ormation of ketone bodies @ acetoacetic acid, betahydro$yl butyric acid and acetone.
!nsulin
1eta cells secrete insulin.
"t is the only hypoglycemic hormone secreted in the body.
"t is polypeptide hormone made up of two chains namely A and 1.
A chain is smaller than 1 chainL the two chains are linked to each other by disulphide
bridges.
"ntravenous in5ection of insulin decreases plasma glucose level to as low as ,= mg>.
"t is not only an anabolic hormoneL it is anti catabolic hormone as well.

Actions of insulin:
2. 'n carbohydrate metabolism
3. -at metabolism
4. Protein metabolism
6. 'n plasma potassium.
32

Action on carbohydrate metabolism)
!t is a hypoglycemic agent.
Decreases blood glucose level.
5ormal fasting blood glucose level is in range of AB1 CB mg>.
Action of insulin on carbohydrate metabolism will be
a. !ncreasing peripheral utili.ation of glucose) "n most of tissues of body, for transfer of
glucose from ;*' to "*' and glycolysis to be brought about inside cell, insulin is
essential. Some of tissues which do not re/uire insulin for peripheral utilization of glucose
are whole of brain e$cept satiety center, %1*s, renal tubules and mucosa of gastro
intestinal tract. 8uring movement of glucose from ;*' to "*', potassium will also be
transferred from ;*' to "*'. 1ecause of this, plasma potassium level falls. "t is for this
reason, when insulin is administered in large doses as it is given in treatment of diabetic
keto acidotic coma, along with insulin potassium should be administered to prevent
hypokalemia and its deleterious effects.
b. "nsulin is also administered if one has to treat cases of hyperkalemia but since insulin is a
very powerful hypoglycemic agent, in treatment of hyperkalemia, along with insulin
glucose also must be given to prevent hypoglycemia and its conse/uences.
c. 0tili.ation of glucose to supply energy and spares proteins from getting
catabolised. This is kno)n as protein sparing effect.
d. !t also increases glucose uptake by liver and enhances conversion of glucose to
glycogen. This is brought about by enhancing activity of glycogen synthease. !lycogen
is stored in liver.
e. !t also decreases glycogenolysis in liver and muscle tissue. So breakdown of glycogen
to glucose will be less.
f. !t decreases gluconeogenesis that is formation of glucose from non carbohydrate
sources like amino acids and fatty acids.
'n protein metabolism: -acilitates transfer of amino acids from EC- to !C-. Amino acids
that have entered the !C- )ill be utili.ed for protein synthesis. At the same time it )ill also
decrease breakdo)n of proteins. "ncorporation of amino acids into proteins leads to retention
of nitrogen in body and brings about positive nitrogen balance. The proteins synthesized will be
33
used for growth of tissues and organs. This facilitates growth, repairing of wounds, ade/uate
resistance against infections -because of immunoglobulins. and gain of weight. "n case child
suffers from 5uvenile diabetes, growth of the child decreases because of loss of aforesaid actions
of insulin on protein metabolism.

'n fat metabolism: !t is a lipogenetic agent. "t acts on adipose tissue and increases the activity
lipoprotein lipase and decreases hormone sensitive lipase activity. This leads to increased
lipogenesis and decreased lipolysis. 'atty acids are transferred from ;*' to "*' in adipose
tissue. These fatty acids are converted to neutral fats and triglycerides and stored in adipose
tissue. 8eposition of fats will increase weight of person. Absence of insulin brings about increase
in free fatty acids levels in circulation. :hen glucose can#t be utilized to supply energy, fatty acids
are metabolized to supply energy. This brings about increased formation of ketone bodies. Such
situation is called as keto acidosis.
6n plasma potassium) Since insulin is involved in transfer of potassium from ;*' to "*', it
decreases plasma potassium level.
/egulation of secretion of insulin:
(. 6ne of the important factors which regulate insulin secretion is plasma glucose level.
0ore is plasma glucose level, more will be amount of insulin secreted. Amount of insulin
secreted for same amount of glucose, depends whether glucose is administered orally or
intravenously. Administration of glucose through oral route brings about enhanced insulin
secretion than intravenous administration.
+. Some of other factors which enhance insulin secretion are amino acids, keto acids,
e$ercise, !" tract hormones, A*h etc.
,. Some of factors which decrease insulin secretion are somatostatin, potassium depletion,
alpha adrenergic stimulation etc.

34

!nsulin lack:
Administration of to$ic substances like allo$an, streptozotocin destroy the beta cells of
islets of 2angerhans and thus lead to insulin lack.
2ack of insulin increases blood glucose -hyperglycemia. level.
:hen blood glucose level e$ceeds (C= mg>, it leads to glycosuria. That is glucose
appears in urine.
Hence the condition is known as diabetes mellitus.
:hen glucose is e$creted, since glucose is an osmotically active substance, it drags
water also with it. This will give rise to polyuria.
"n hypothalamus, there are two centers namely hunger center which is located in the
lateral hypothalamic nucleus and ventro medial nucleus which acts as satiety center.
&ormally hunger center activity is under constant inhibitory influence from satiety center.
The utilization of glucose by satiety center is dependent on insulin. :hen insulin is
absent, activity of satiety center is depressed. 1ecause of this, the inhibition of hunger
center by satiety center is decreased -disinhibition.. &ow hunger center activity becomes
unopposed and gives rise to increased hunger and hence polyphagia.
Pathophysiology of diabetes mellitus:
Diabetes mellitus can be of t)o types namely type ! or insulin dependent diabetes
mellitus +!DD(, and type !! or non insulin dependent diabetes mellitus +5!DD(,.
:hatever may be the type of diabetes there will be fault in glucose metabolism.
8ecreased peripheral utilization and increased hepatic glycogenolysis brings about an
increase of blood glucose level.
"ncreased blood glucose -above renal threshold of (C= mg >. level leads to glycosuria.
!lycosuria leads to polyuria -increased urine e$cretion. since glucose is an osmotically
active substance. This type of polyuria differs from polyuria of diabetes insipidus because
in diabetes insipidus, diuresis is termed as water diuresis -because of decreased amount
of water reabsorption by renal tubules. and specific gravity of urine will be low.
"ncreased loss of water along with urine leads to dehydration and resulting in stimulation
of thirst center and hence there will be polydypsia -increased drinking..
Dnopposed activity of hunger center results in polyphagia -increased eating..
Since blood glucose level is more and body protein content is less, the person is more
susceptible to infection and poor wound healing.
"ncreased protein catabolism leads to weight loss and poor growth. Amino acids which
are the end products of protein catabolism will be used for gluconeogenesis.
"n the absence of glucose getting metabolized to supply energy, fat catabolism increases
and this gives rise to lipolysis. 1eta o$idation of fatty acids brings about increased
formation of ketone bodies and lead to keto acidosis. 3etone bodies can be e$creted
35
along with e$pired air and hence breath of these patients will have characteristic apple
odor.
Some of the cardinal symptoms of diabetes


Tests for diabetes mellitus:
2. Test for glucose in urine.
3. Test the fasting blood glucose level.
4. Perform oral glucose tolerance test +8TT,.
*oma is one of the serious problems of imbalance in glucose metabolism. erson may get into
coma either because of hyperglycemia or hypoglycemia. 6ne of the e$amples of hypoglycemic
coma is improper management of diabetes in patients. Among the t)o types of coma*
hypoglycemic coma is more dangerous.
The signs and symptoms of hypoglycemic coma are:
(. 8izziness and nervousness due to
increased autonomic discharge
+. alpitation
,. Sweating
7. :eakness
<. Ata$ia that is incoordination of
movements.
I. *onfusion
?. &ervousness and apprehension.
C. Tremors.
B. Slurred speech.
(=. convulsions
How to differentiate whether coma is because of hypo or hyperglycemiaM
<hen comatose patient is brought emergency room* time should not be )asted. Treatment
to the patient has to be started as early as possible. 6ne of the first and foremost things to be
done is, )hen not certain that coma is due to hypo or hyperglycemia* infuse glucose
intravenously. "f coma is because of hypoglycemia, patient recovers without any further
procedure. "f coma is due to hyperglycemia, patient will not recover and infusion of glucose would
not harm the patient anymore. &ow the treatment has to be initiated to manage the
hyperglycemic coma.
36
Coma in e%treme glycemic states
yperglycemic ypoglycemic
Dnconsciousness 999 999
8anger 2ess 0ore -medical emergency.
*&S 8epressed Stimulated
1lood glucose High 2ow
!lucose in urine 999 Absent
3etone bodies in urine 999 Absent
*ause oor management of diabetes 6verdose of antidiabetic drugs
Treatment "nsulin administration, correct
acidosis, correct fluid balance,
potassium administration
"ntravenous glucose
administration
Some of the conditions in )hich glycosuria occurs are)
(. 8iabetes mellitus due to problem in glucose metabolism
+. %enal glycosuria due to problem in decreased glucose reabsorption by renal tubules
,. Alimentary glycosuria occurs in hyperthyroidism. "n hyperthyroidism, rate of absorption of
glucose from !" tract is enhanced and this may lead to glycosuria.
8lucagon
"s a peptide hormone.
Secreted by alpha or A cells of islets of 2angerhans.
Dnlike insulin which is a hypoglycemic agent, glucagon is a hyperglycemic agent.
Actions:
2. Carbohydrate metabolism
3. -at metabolism

6n carbohydrate metabolism)
"s a hyperglycemic agent and hence increases blood glucose level.
1rings about glycogenolysis in liver only. !lucose produced by glycogenolyis is added to
circulation.
"ncreases gluconeogensis is liver.
37
6n fat metabolism)
"t is a lipolytic agent.
Acts on adipose tissue and increases the activity of hormone sensitive lipase.
This brings about increased lipolysis. 'ree fatty acids are added to circulation due to
breakdown of neutral fats and triglycerides.
Dtilization of fatty acids to supply energy may lead to ketone body formation.
/egulation of secretion:
2evel of blood glucose in circulation affects secretion of hormone. 8ecrease in blood glucose
level will increase the secretion of glucagon and vice versa when level of glucose is increased in
circulation. Apart from this some other factors which can affect the secretion of glucagon are)
Stimulators are)
"ngestion of proteins.
Sympathetic stimulation
6ne of the important factors which decrease secretion of glucagon is somatostatin.
Parathyroid gland and calcium and phosphate metabolism
"onic calcium plays an important role in our body. Hence its concentration has to be very well
regulated.
Total calcium present in the body in young human adult is about ((== g. 6f this about BB> is
present in bone. The plasma calcium level is about B @ (( mg>. Appro$imately <=> of this is in
ionic form and rest is present in bound form, bound either to plasma proteins or as citrates.

-unctions of ionic calcium:
(. (aintenance of /(P) 1ecause of this, the e$citability of neuron and muscle is
maintained. 8ecrease in calcium ion level increases e$citability and vice versa when
calcium ion level decreases.
+. 51( transmission) lays an important role in conduction of impulse across neuro4
muscular 5unction. Amount of A*h released is directly dependent on /uantum of calcium
ion influ$ at the pre synaptic terminal.
,. (aintenance of e%citability and contractility of cardiac muscle: lateau phase of
action potential of cardiac muscle and for contraction of cardiac muscle ;*' calcium ion
is necessary.
7. >lood coagulation) "n many of the steps of blood coagulation calcium ion is re/uired.
8ecreased level of calcium ion in circulation fails to clot blood normally. 'actor N7
7. Development of bone and teeth
38
I. "s re/uired for activation of certain enzymes
?. "s re/uired for release of certain hormones.
*alcium is actively transported from !" tract. The most important factor influencing calcium
absorption is (4+< dihydo$y cholecalceferol. 6ther factors which can also influence calcium
absorption are growth hormone, acidic pH in duodenum. *alcium absorption is decreased in old
age. 2arge amount of calcium is filtered in the kidneys and about BB> of filtered calcium is
reabsorbed. About I=> of reabsorption occurs in *T and the rest from 8*T.


*alcium present in bone are two types namely easily e$changeable compartment and in much
stable compartment. *alcium that is present in plasma and bone are in e/uilibrium. :hen plasma
calcium level increases suddenly, calcium is removed from plasma to get deposited in the bone
along with phosphate. :hen plasma calcium level falls, calcium is removed from bone matri$ by
process of demineralization and this calcium enters plasma.
hosphate) Total body phosphate is about <== 4C== g, of this C< 4B=> of this is present in bones.
Total plasma phosphate level is about (+ mg>. About (/,
rd
of this is in inorganic form mostly as
67
,
, H67
+
and H+67. About , mg of phosphate enters bones everyday and an almost e/ual
amount of this is removed from the bone.

hosphate is filtered into renal tubules and C< to B=> of this gets reabsorbed. 0ost of this
reabsorption occurs at *T and is by active process. :hen parathormone acts on the renal
tubules, amount of phosphate reabsorbed is decreased. "n !" tract phosphate absorption occurs
both actively and passively in duodenum. 'actors that increase calcium absorption also increase
phosphate absorption
39


1one is special form of connective tissue. 6n collagen framework, calcium and phosphate are
deposited in the form of hydro$yl appatite crystals. 8eposition and resorption of calcium and
phosphate ions proceed continuously in bone matri$. "n young people, deposition of salts occurs
to greater e$tent than resorption and in elderly people it is reversed.
The cells responsible for bone formation are osteoblasts. 6steoclasts are responsible for bone
resorption. 6steoclastic activity is associated with increase in alkaline phosphatase activity.
Third type of cell found in bone matri$ is osteocyte. These cells are responsible for transferring
large amount of calcium from interior to e$terior -;*'..
Parathyroid glands
They are four in number. Two are in the superior and two are in inferior poles of thyroid gland in
posterior aspect. arathyroid glands are essential for basic survival. %emoval of the gland can
lead to death of the person. This is because, removal of the gland decreases plasma calcium
level and there will be increase in e$citability and contractility of nerve and muscle tissue. The
increased e$citability will lead to laryngeal muscle spasm, asphy$ia and death.
Histology of parathyroid gland) Two different types of cells are seen. (. *hief cells and +. 6$yphil
cells. The chief cells are responsible for secretion of parathormone -TH..
TH is a polypeptide hormone with molecular weight of about B<== and contains about C7 amino
acids.
Actions:
"t is a hypercalcemic and hypophosphatemic agent. Hence increases plasma calcium level and
decreases plasma phosphate level. The important sites of actions of PT are
2. >one
3. Didney
4. 8! tract in an indirect )ay.
PT and bone: it acts on the bone matri$ mobilizing calcium and phosphate by resorption of the
osseous tissue. To start with, it is supposed to increase the activity of osteocytes. This is followed
by increase in number of osteoclasts. This increases osteoclast cells activity. 8uring this process
hydrogen ion concentration of the bone fluid is increased. This brings about solubility of the
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calcium and phosphate and they are removed from protein matri$. This brings about
osteoporosis. *ontinued action of TH on bone will lead to pathological fractures.
"nitially TH acts on osteocytes and increases transfer of calcium ions from bone fluid into ;*'.
A slow but in more sustained way it acts on the osteoclasts which are responsible for resorb
calcium and phosphate from the more mature bone. Activity plus the number of osteoclasts are
increased by TH -citric acid 9 lactic acid production is increased, this increases the H
9
-proton.
concentration in the bone. The resultant increase in the H
9
, facilitates the process of calcium and
phosphate removal. TH in low dose facilitates action of osteoblasts thus stimulating bone
formation.


PT and kidney:
2. !ncreases the calcium reabsorption from DCT.
3. Decreases phosphate reabsorption from PCT.
4. Stimulates the activity of 2 alpha hydro%ylase activity, which in turn brings about
increased formation of (4+< dihydro$y cholecalcefrol -active form of vitamin 8..
(. "ncreased reabsorption of calcium from 8*T and the action is immediate. *yclic A0 is
involved in this process. 0ore of filtered fraction of calcium is reabsorbed. The amount of calcium
e$creted in the urine decreases. As the plasma calcium is increased, filtered load of calcium also
increases. This may give rise to increased e$cretion of calcium in urine which may lead to
formation of renal stones.
+. 8ecreases the reabsorption of phosphate from *T. Therefore there will be increased
e$cretion of phosphate in urine. "t may also decrease reabsorption of sodium and bicarbonate.
,. "ncreases production of (4+< dihydro$y cholecalceferol -(4+< 8H**.L
TH and !" tract) The action on !" tract is indirect one. "ncreased formation of (4+< 8H** in turn
facilitates more of absorption of calcium from duodenum.
/egulation of secretion of PT and calcitonin:

41
8ecrease in plasma calcium level increases TH secretion and when plasma calcium level
increases, there will be increased secretion of calcitonin.
Apart from the plasma calcium level, some of the other factors which can affect the secretion of
TH are
(. 8ecreased plasma magnesium level.
+. "ncreased plasma phosphate level
,. (4+< 8H** inhibit the TH secretion.
yperparathyroidism: in primary hyperparathyroidism* increased secretion of TH is
associated with hypercalcemia and hypophosphatemia. This results in decreased e$citability of
neuro muscular tissue. Associated with this will be pathological fractures, osteoporosis, removal
of calcium from gingival margin, formation of renal stones, and deposition of calcium in the soft
tissues and along the blood vessels.
Secondary hyperparathyroidism is due to chronic renal diseases associated with e$cessive
calcium loss. 8ecreased calcium level in plasma stimulates e$cessive secretion of TH.
yperparathyroidism features are:
6steitis fibrosa cystica
Hypercalciuria
%enal stones
Hypercalcemia
Hypophosphatemia
8emineralization of bones
ypoparathyrodism: is due to inadvertent removal of these glands during thyroidectomy.
Hypoparathyoridism can lead to development of hypocalcemic tetany.
Tetany is of t)o types namely 2. 'vert tetany and 3. #atent tetany.
!n latent tetany, the clinical manifestations of tetany are not obvious, but may be brought out by
hyperventilating the lungs. Hyperventilation brings about carbon dio$ide washout which leads to
alkalosis -washing out of hydrogen ions from the body.. This leads to decreased ionic calcium
level in plasma.
"n latent tetany, mild tapping on the facial nerve at the angle of 5aw, leads to prolonged painful
contraction of ipsilateral facial muscles. This sign is known as *hvostek#s sign. *arpopedal
spasm can be produced by applying 1 cuff and increasing pressure in the cuff. "ncreasing
pressure in the cuff obstructs blood flow. This sign is known as Trousseau#s sign.
!n overt tetany there will be marked increase of neuro muscular e$citability with twitching, tonic
and clonic contractions of muscle fibers. *ontraction of laryngeal muscles will give rise to
asphy$ia and death.

-eatures of hypocalcemic tetany are)
(. &umbness @ tingling of the
e$tremities -paresthesia.
+. Stiffness of hand and feet.
,. *ramps in the e$tremities.
7. *onvulsions in children.
<. *hvostek#s sign
I. Trousseau#s sign -carpo pedal
spasm..
?. 2aryngeal spasm.
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Treatment: <hen the patient has overt tetany* intravenous calcium should be given. 'n
long term basis* diet rich in calcium and vitamin D must be given.
Calcitonin
"n human beings calcitonin is produced from the parafollicular cells -* cells. of the thyroid gland.
*alcitonin is made up of ,+ amino acids with molecular weight of ,<==. !t is a peptide hormone
secreted by the parafollicular cells of thyroid gland.
Actions: "t is hypocalcemic agent and hence decreases plasma calcium level. :hen thyroid
gland is perfused with blood containing high calcium, secretion of calcitonin is increased. This
lowers plasma calcium and phosphate levels. *alcium lowering effect of calcitonin is brought
about by its action on bones. "t prevents calcium resorption from bone. "t inhibits activity of
osteoclasts and increases e$cretion of calcium in urine.
/egulation of secretion) is directly dependent on plasma calcium level -refer graph given for
regulation of secretion of parathormone in earlier pages.
-actors )hich influence calcitonin secretion are:

Hypo or hypersecretion of calcitonin is not associated with any clinical abnormality. 0edullary
carcinoma of thyroid gland is associated with increased production of calcitonin, but no signs and
symptoms are seen in this hyper state of calcitonin secretion. "t has been shown that
comparatively more hormone is secreted in young individuals. "t may be help for deposition of
calcium on bone and facilitates bone growth. 8iet rich in calcium when given, gastrin which is
released in gastric phase of gastric 5uice secretion may stimulate calcitonin release as well.
"ncreased release of calcitonin diverts calcium to bone tissue thus preventing e$cessive rise in
plasma calcium level. "t may also protect mother from e$cessive drainage of calcium during
pregnancy and lactation. The e$cessive drain of calcium during pregnancy may be due to
increased level of (4+<8H**.

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