Endocrine System

Dr. Paras Parekh

Professor
GAIMS, Bhuj
Our Journey
[Link] Principles of Endocrine system
[Link] & Pituitary
[Link]
[Link] glands
[Link] and GI hormones
[Link] & Calcium metabolism
General Principles of Endocrine
system
 Hormone:
- Greek word, hormaein means ‘to arouse’
- Secretory molecules transported by circulatory
system to target distant organs where they regulate
morphology and behavior
- Messengers
 Classifications of Hormones

Endocrine Paracrine Autocrine

 Classifications of Hormones

Amine Protein Steroid

-Catecholamine - Insulin, Glucagon - Glucocorticoids
-T3, T4 - Parathormone - Mineralocorticoids
- Anterior & Posterior - Sex steroids
Pituitary - Vitamin D
(PPP)
 How hormones act on target cell?
Some hormones have easy entry in target cell (e.g.
steroid & thyroid)

where receptors are waiting for them (In cytoplasm

for steroid & on nucleus for thyroid)
Action through Gene expression
Some hormones (Proteins) have no entry in cell, so
they just pass message to their receptor on cell
membrane (so they are first messenger)

Some machineries are activated

Production of second messenger is started, which

brings metabolic change in the cell
 Machineries?
1) G Protein coupled receptor
2) Activation of some Enzymes
G Protein coupled receptor
 Activation of some Enzymes
- Adenylyl cyclase
- Guanylyl cyclase
- Phospholipase
- Tyrosine Kinase
Production of second messenger
- cAMP
- cGMP
- IP3 (Inositol triphosphate)
- Calcium
- New mRNAs
Adenylyl cyclase-cAMP system
Membrane Phospholipase system
 Transport of Hormones
- Thyroid & steroid hormone need binding proteins
for transport in plasma
- Around 90% are in bound form
- Free form is the biological active form of hormone

Note: Concentration of plasma protein affect

hormone activity
While measuring hormone level, it is important
to measure free and bound form separately….
 Regulation of Secretion

1) Negative or Positive feedback control

Hormone to Hormone feedback
Substrate to Hormone feedback (e.g. Glucose)
 Regulation of Secretion
2) Neural control:

- External stimuli like visual, auditory, tactile etc.

(Crying of baby stimulate secretion of oxytocin in
mother for milk ejection)

-Internal stimuli like emotion, pain, fright, stress,

blood volume change etc.
 Regulation of Secretion
3) Other regulatory mechanism like
- Diurnal variations
- Menstrual cycle rhythm
- Seasonal variations
 Measurement of Hormone
Commonly used methods…
ELISA
Radioimmunoassay

Other methods..
Cytochemical assay
Bioassay
Hypothalamus
&
Pituitary
 Hypothalamus
The Master Controller of the Endocrine Orchestra..
 Hypothalamus
- The master controller
- Link between endocrine & nervous system

Receive afferent signal from thalamus, RAS,

limbic system, special senses and send efferent
signal to the pituitary via hormones
Hormones produced by Hypothalamus
Hormones controlling anterior pituitary:
Releasing hormones- GHRH, TRH, CRH, GnRH, PRH
Inhibitory hormones- GHIH, PIH

Hormones of posterior pituitary: ADH, oxytocin

Other hormones- Neuropeptide Y, Orexin, MCH

Pituitary gland (Hypophysis cerebri)
0.5
gram,
1 cm
Hypothalamo-Pituitary relation
Adenohypophysis-

Acidophil Basophil
- Somatotroph (GH) - Thyrotroph (TSH)
- Mammotroph (Prolactin) - Corticotroph (ACTH)
- Gonadotroph (FSH,LH)

Control via Hypothalamo-hypophyseal portal system

GH family Glycoprotein Pro-opiomelanocortin
family family
GH TSH ACTH
Prolactin FSH MSH
LH β-endorphin

MCQ Ahead
Neurohypophysis:

- Neuroectodermal extension of hypothalamus

- Connected to Supra-optic & Paraventricular nucleus
of hypothalamus
- Oxytocin & ADH
- Hypothalamo-hypophyseal tract
Growth Hormone (Somatotropin)
 Growth Hormone (Somatotropin)
- Released in pulsatile manner
- Increased during sleep- peak at 1 or 2 hour after
deep sleep- 70% of daily secretion

‘Adequate sleep is
necessary for growth’
When GH secretion Increase?
- Hypoglycemia (Fasting)
- After high protein diet
- Exercise
- Stress
- Sleep
- Pain
- Puberty
When GH secretion Decrease?
- Hyperglycemia
- High FFA
- Obesity
- Sleeplessness
How GH work on target cell?

JAK- Jannus
Kinase

STAT- Signal
transducer &
activators of
Transcription

JAK-STAT
Pathway
 Actions of GH

Growth promotion: (Linear growth)

- Proliferation of chondrocytes
- Osteoblast stimulation (till fusion)
- Increase in bone mineralization

Promotes milk production in lactating animal

 Metabolic effect of GH
Carbohydrate Lipid Protein

+
- Hyperglycemic
-
- Promote fat
+
- Build Muscle Mass
utilization
Negative feedback control
 Disorders of GH
Hyper-secretion:
- Tumor of somatotrophs
- Before closure of epiphysis Gigantism
- After closure of epiphysis Acromegaly

Hypo-secretion:
- Dwarfism
 Gigantism
- Abnormal height
- Large hands &
feet
- Coarse face
- Macroglossia
- Gynaecomastia
- Loss of libido
- Hyperglycaemia
 Acromegaly
- Coarse face
- Broad nose
- Prognathism
- Prominent eye-brows
- Large hands & feet
- Height may be normal
- Enlarged organs
Dwarfism
 Dwarfism
Endocrinal dwarf Non-endocrinal dwarf
Causes are: Achondroplasia
Malnutrition
GH deficiency Turner’s syndrome
Hypothyroid dwarf
Panhypopituitarism

Proportionate Non-proportionate
Pituitary dwarf: due to GH deficiency in childhood
- Short stature (Proportionate)
- Normal mental activity
- Fatness

Note: Features of thyroid dwarf are same except

thyroid dwarfs are mentally retarded
 Human Prolactin
- Acidophil cells
- Mechanism of action same as GH

Controlled by hypothalamus through by PRH and PIH

(Dopamine)

Pregnancy Rise from 8th week and peak at term

Sucking
nipple
by baby-
Strongest
stimulus

Stress
suppress
Prolactin
secretion
Functions of prolactin:
- Initiation & maintenance of Lactation
- Growth of duct & alveoli in Breast
- Synthesis of lactose, casein & lipids from alveolar
epithelial cells in Breast
- Affection with new born

- Suppression of ovarian cycle in nursing mother (by

inhibiting GnRH), acts as contraception
- Lactational amenorrhea
Hyperprolactinemia
Tumor (Prolactinoma)
Certain medicines (e.g. Antipsychotics)

In women → infertility, irregular menstruation,

Galactorrhea
In men → infertility, erectile dysfunction, Gynecomastia &
Galactorrhea
Posterior Pituitary
Hormones
 Anti-diuretic hormone (Vasopressin)
Synthesize by supraoptic (more) and paraventricular
nucleus of hypothalamus

Three receptors → Three different actions

V1-A receptor- Blood vessels (vasoconstriction)
V1-B receptor- Anterior pituitary (ACTH)
V2 receptor- Kidney (Anti-diuresis)
Other actions
Vasoconstriction Increase blood pressure (V1-A)
Increase ACTH secretion from anterior pituitary (V1-B)
Glycogenolysis in liver
Act as neurotransmitter and involve in regulation of
temperature, blood pressure, circadian rhythm and
memory (V1-A)
 Regulation of ADH
By two factors:
1) Change in plasma osmolality
2) Change in blood volume
 Change in Plasma Osmolality (Potent)
Water deprivation

Increase plasma osmolality (by 1-2% only)

Shrinkage of osmoreceptors (Neurons of anterior hypothalamus)

Increase discharge of osmoreceptors & ADH secretion

 Change in Blood volume
Low volume or low pressure → sensed by volume
receptor (in atria & veins) and pressure receptors
(Baroreceptor) → stimulation of SO & PV nucleus
→ production of ADH
Factors increasing ADH secretion
- High osmolality
- Low blood volume
- Low blood pressure
- Pain
- Stress
Factors decreasing ADH secretion
- Low osmolality
- High blood volume
- Alcohol
 Applied 1: SIADH
Causes:
- Head injury
- Ectopic source like bronchogenic carcinoma
- Infection in nervous tissue
- Side effect of some drugs (Anticonvulsants, antidepressants etc.)
(Importance of history)
Features:
- Water retention
- Hyponatraemia (Also hypernatriuria)
- Oedema
 Applied 2: Diabetes Insipidus
Deficiency of ADH or decrease renal response of ADH

Central or neurogenic DI Nephrogenic DI

Failure of ADH secretion Failure of renal response to ADH
Congenital, surgery, head Defective V2 receptors
injury etc.
Oxytocin
 Oxytocin
- More from Paraventricular nucleus

- Act via secondary messenger system by increase in

intracellular Ca2+ level
Stimulatory factors:

- Suckling in breast feeding

- Cervix dilatation during labor
- Genital stimulation during sex

Milk ejection reflex & Parturition reflex

 Milk
ejection
reflex
New Mother
need warmth
& support so
she can have
the best
bonding with
her baby.
Thyroid hormones
 List of thyroid related diseases
Hypothyroidism
Cretinism
Hyperthyroidism
Thyrotoxicosis
Grave’s disease
Goiter
Thyroiditis
Hashimoto’s disease
Thyroid nodules
Thyroid Cancer
Thyroid Storm
Hormones
T4 (Thyroxine) – 90% of thyroid output (inactive)
T3 (Triiodothyronine)- 10% (active form)
Calcitonin
Reverse T3- biologically Inactive

T4 → T3
 Synthesis of Thyroid hormone
Raw material- Tyrosine, Iodide, Thyroid Peroxidase

Iodine is ingested in iodide form

Sources are iodized salt, sea fish, milk and
vegetables
1) Iodine trapping-

- Uptake of iodide by thyroid gland

- Enter in follicular cell via I/Na symporter
- Active process (Require ATP), so linked with
Na-K ATPase pump
- Uptake controlled by TSH
2) Oxidation of Iodide:

-Iodide move towards lumen side and released in

lumen through Pendrin
-Iodide is oxidized to iodine by Thyroid
peroxidase (Organification)
-TSH stimulate this step

Pendred Syndrome
3) Synthesis of Thyroglobulin:

- One molecule made from 70 tyrosine (Reference-

Guyton)
- Synthesized on rough EPR
- Move to membrane and released in to lumen of
follicle
4) Iodination of Tyrosine:

-Tyrosine present in TG is iodinated at position 3,

forms monoiodotyrosine (MIT)
-Then at position 5 to form diiodotyrosine (DIT)
-Presence of thyroid peroxidase is required
5) Coupling reaction:
- DIT+DIT= Thyroxine (T4)
- DIT+MIT= Triiodothyronine (T3)
- Presence of thyroid peroxidase is required

6) Storage:
- After iodination of TG, it is stored in lumen of
follicle as colloid for months
 Secretion of Hormones:
-TG enters from lumen of follicle to cell by
endocytosis, through ‘Megalin’
-In cell, lysosome breaks bonds in TG molecule
and release T3, T4, DIT, MIT
-T3, T4 enters blood stream
-DIT, MIT deiodinated by Deiodinase
 Fate of Thyroid hormone
99.95% of T4 & T3 circulate in bound form,
Binds with….
- Thyroxine binding globulin (70%), Thyroxine
binding prealbumin (20%), Thyroxine binding
albumin (10%)
0.05% circulate in free form (the biologically
active form)
 Peripheral conversion
- T4 into T3 by the enzyme 5- deiodinase

Any drug (e.g. Antiarrythmic) or disease affecting

this enzyme will indirectly affect thyroid action
 Regulation of Thyroid hormone
Negative feedback mechanism
- Feedback to TSH & TRH
- Cold, Emotion, stress, anxiety, etc.

Dietary iodine
Measurement of TSH is important along with
T3 & T4 level…..Why?
Mechanism of Action
Actions of Thyroid hormone
 Growth & development
- Stimulate gene expression for GH
- Stimulate chondrocytes & osteoid activity (linear
growth)
- Growth of teeth, nails & hairs
 Metabolism & Heat production
- Stimulate basal metabolic rate & basal oxygen
consumption
- Stimulate Na-K ATPase pump activity
- Stimulate mitochondrial enzymatic activity
- Uncoupling of oxidative phosphorylation leads to
heat production (Thermogenic)
 Metabolism & Heat production
- Stimulate food intake
- Stimulate consumption of nutrients

Decrease food intake in hypothyroidism &

voracious appetite in hyperthyroidism……
 Effect on Metabolism
Carbohydrate:
- Increase turnover of Glucose (Production as well as
utilization)
Lipid:
- Lipolysis
- Decrease cholesterol by increase hepatic uptake &
biliary excretion (Chronic hypothyroidism →
atherosclerosis)
Protein:
- Increase turnover
Weight gain occurs in hypothyroidism (despite
decrease food intake)

Weight loss occurs in hyperthyroidism (despite

voracious appetite)
THYROID
 Effect on Nervous system
Stimulates……
- neuron maturation
- neuronal connections
- Synapse formation
- Myelination
- Neurotransmitter synthesis
- Alertness, memory, learning, speed of reflex etc.
Mental retardation occurs if there is hypothyroidism
during infancy & childhood…

Tremor occurs in hyperthyroidism….

 Effect on RS
- Stimulates basal respiratory drive
- Increase in rate & depth of respiration
- Increase minute ventilation

(Tachypnea in hyperthyroidism & bradypnea in

hypothyroidism)
 Effect on CVS
- Stimulates basal heart rate
(Tachycardia during sleep → important sign of
hyperthyroidism)
- Stimulates myocardial contractility
- Stimulates stroke volume
- Increase systolic BP

Diastolic BP decrease…….. How?

 Effect on GIT
- Stimulates GI motility
- Stimulates GI hormone secretion

Constipation → symptom of hypothyroidism

Diarrhea → symptom of hyperthyroidism
 Effect on Renal system
- Stimulate RBF
- Stimulate GFR
- Stimulate reabsorption process
 Effect on skeletal muscle
- Support muscle contraction process

Hypothyroidism → Muscle weakness & cramp

Hyperthyroidism → Thyrotoxic Myopathy, muscle
weakness due to protein catabolism
 Effect on reproductive function
- Support follicle maturation & ovulation
( Irregular periods → common complain in hypo & hyper
thyroidism)

Menorrhagia or Polymenorrhea → Hypothyroidism

Oligomenorrhea or amenorrhea → Hyperthyroidism

- Loss of libido or impotency in male

- Infertility
 Effect on sleep
Insomnia → Hyperthyroidism
Extreme somnolence → Hypothyroidism
Why excessive sweating occurs in
Hyperthyroidism?
Applied
 High thyroid
Hyperthyroidism

Severe form → Thyrotoxicosis (Grave’s disease)

Toxic goiter, Toxic nodular goiter

Thyroiditis or Thyrotoxicosis factitia

 Hyperthyroidism
Primary: (Problem in Thyroid)
- Adenoma, Autoantibodies like TSH, drug
overdose, Metastatic carcinoma

Secondary: (Problem outside Thyroid)

- Pituitary tumor, Ectopic secretion
Grave’s disease
Nodular Goiter
 Hypothyroidism
Primary: (Problem in Thyroid)
- Iodine deficiency, Autoimmune (Hashimoto’s
disease), Surgical removal, Excess antithyroid
drugs, congenital

Secondary: (Problem outside Thyroid)

- Pituitary or hypothalamic deficiency, receptor
resistance
Hypothyroidism in Childhood (Cretinism)
Hypothyroidism in adult (Myxedema)
Hashimoto’s Thyroiditis:
- Autoimmune condition
- Antibodies against Thyroglobulin

Wolff-Chaikoff effect:
- Hypothyroidism due to excess iodine
- Iodine prevents its own organification
 Hyperthyroidism Hypothyroidism
BMR BMR
Weigh loss despite Weight gain despite
increase appetite decrease appetite
Heat production, Heat production,
intolerance to heat intolerance to cold
Sweating Sweating, dry skin
Tachycardia, atrial Bradycardia
fibrillation
 Hyperthyroidism Hypothyroidism
Restless, irritable, Lethargy, sleepiness, slow
psychosis, tremors of hand movement, slow speech
Reflex-exaggerated Reflex-slow down
Diarrhoea Constipation
Oligomenorrhoea, Polymenorrhoea
Amenorrhoea Menorrhagia
Infertility Infertility
Grave’s disease characteristic features-
Exopthalmos
Retro orbital swelling due to inflammation and fibroblast
deposition in orbit and extra occular muscle, increase
pressure in eye globe
Myxedema characteristic features- Yellowish tinge
in skin, puffy face, hoarse voice, non pitting
oedema
Yellowish tinge→ due to carotenemia
Puffy face with baggy eyes → due to water retention
& weight gain
Hoarse voice→ due to fluid deposition in vocal cord
& pressure by enlarged thyroid gland
Non pitting edema→ Formation of tissue gel due to
deposition of hyaluronic acid & chondroitin sulfate
 Hyperthyroidism Hypothyroidism
Primary: T3, T4 Primary: T3, T4
TSH TSH
Secondary: T3, T4 Secondary: T3, T4
TSH TSH
Treatment: Treatment:
Antithyroid drugs Life-long replacement
Surgical removal therapy with
Radioactive ablation L-thyroxine
Thyroid function test (SDL)
Calcium
Balance
Total plasma calcium- 9-11mg/dl

4 mg/dl- bound form with albumin

5 mg/dl- Ionized form (active)
1 mg/dl- complexed with Hco3-, citrate

Calcium balance in tight narrow margin

Why calcium is so important?
- Cell division & cell function
- Nerve excitability control
- Muscle action potential
- Cardiac pacemaker potential
- Bone mineralization
- Blood Coagulation
- GI motility
- Hormone action (as second messenger)
- Neurotransmitter release
Calcium balance is affected by…..
Three hormones:
- Parathyroid hormone, Calcitonin, Vitamin D3

Three organs:
- Bones, Kidney, Intestine
Calcium balance is maintained by inter play of 3
processes

1) Absorption from GIT

2) Exchange between bone & ECF
3) Excretion
 Diet
1000 mg
Exchangeable
350 mg Rapid pool
ECF 20,000
4000 mg

GIT 1000
150 mg BONE
mg
Slow Stable pool
10 lacs mg
Filter 500 mg
10,000
Fecal Excretion ( Reabsorb
800 mg KIDNEY 9800 mg
Urine Excretion
200 mg
Parathyroid Hormone
Mechanism of action:
- Act by two mechanisms:
1) Adenylyl cyclase-cAMP system
2) Phospholipase- IP3 system

- Target organs are bone, kidney, GIT

- Associated with maintenance of plasma calcium level

(Increase plasma calcium) & also decrease plasma
phosphate level
Regulation of PTH
PTH α 1
----------------------
Ionized Calcium

Increase in plasma phosphate fall in plasma

calcium rise in PTH
Vitamin D3 inhibits PTH
Function of PTH
Action on bone:
- Bone resorption (Demineralization)

Rapid phase by mobilization of calcium from bone to ECF

Slow phase by stimulation of Osteoclastic activity (size &

number)
 Action on Kidney:
- Calcium reabsorption from loop of Henle & DCT
(minor effect)
- Phosphate reabsorption in proximal tubule
- Stimulate synthesis of Vitamin D3

Action on Intestine:
- Calcium absorption from intestine (indirectly by
vitamin D3)
 PTH

Vitamin D3
Hyperparathyroidism:
Primary- Parathyroid adenoma
Secondary- Chronic renal failure

Clinical features:
Hypercalcemia, calciuria, renal stones
Muscle weakness, lethargy
Constipation, peptic ulceration
Hypertension, arrhythmias
Bone pain, fracture
 Hypoparathyroidism:
True- Damage to parathyroid gland during
thyroidectomy
Pseudo- Defective receptors, congenital

Clinical features:
Hypocalcaemia causing ‘Tetany’
Hyperphosphataemia
 Tetany (muscle spasm)
When ionized calcium falls to 50%

How Tetany develop?

Ca2+ maintain integrity of cell membrane, When it
decrease permeability to Na+ increase in neuronal
membrane series of action potential
Signs & symptoms of Tetany:
1) Carpopedal spasm

2) Laryngeal stridor: Loud sound & asphyxia

3) Trousseau’s sign:
Occlusion of blood supply to limb produce carpal spasm
4) Chvostek’s sign:
Tapping of facial nerve produce twitching of facial muscle

Treatment: Intravenous Calcium gluconate

 Calcitonin
Parafollicular C cells
Decrease plasma calcium level
Site of action is bone and kidney
On Bone: Reduce osteoclastic activity and oppose action
of PTH
On Kidney: Increase calcium and phosphate loss In urine
Protect bones of children and mother during pregnancy
against calcium loss

Used as treatment for acute hypercalcemia

 Vitamin D3
Action on GIT: (Major site)
- Increase calcium absorption

Action on Bone:
- Bone mineralization via osteoblast
- Also secondary osteoclastic activity but it is overshadowed

Action on Kidney:
-Increase renal reabsorption
Why person with lack of vitamin D is prone to
infection?

Calcitriol helps in stimulation & differentiation

of immune cells. It also regulates activity of
helper T cells.
Hormones of Heart
Hormones of Kidney
Adrenal Hormones
Mineralocorticoids:
- Aldosterone
- Deoxycorticosterone
Glucocorticoids:
- Cortisol
- Corticosterone
Sex steroids:
- Dehydroepiandrosterone
- Androstenedione
Synthesis of Adrenal Cortex Hormones
 Fate of adrenocortical hormones
90 % in bound form:
- with corticosteroid binding globulin (Transcortin)
(80%)
- with albumin (10%)
Glucocorticoids
(Anti-stress hormone)
Mechanism of action
Circadian pattern of Cortisol
 Regulation of Glucocorticoids

Stress is any Stress

condition in which
ACTH secretion is Limbic system
Increased.
Hypothalamus

CRH
Never withdraw steroid abruptly after chronic
use….
 Actions of Cortisol

Shield against Stress, Inflammation, Allergy, Fasting

 Metabolic action of Cortisol
Carbohydrate Lipid Protein

+
- Hyperglycemic
-+ -
- Lipolytic - Catabolic

All these actions are for synthesis of Glucose

Chronic elevated cortisol Hyperglycemia
Increase insulin Lipogenic effect

Lipogenesis occurs in central fat store only, creates

characteristic picture (Central obesity)

Moon face, Buffalo hump, Pot belly with thin limbs

Cortisol→ Stimulates Neuropeptide Y in
hypothalamus → Stimulates food intake

Chronic high cortisol can cause obesity….

Effect on bones: (Catabolic)
- Osteoclastic activity
- Bone formation by inhibiting osteoblastic activity, decrease
collagen synthesis, decrease calcium absorption by decreasing
vitamin D

Effect on muscle: (Catabolic)

- Muscle mass by proteolysis
Effect on connective tissue: (Catabolic)
- Collagen synthesis leads to thinning of skin &
capillary walls

Minor injury creates bruises in chronic cortisol

excess…..
5) Effect on CVS:
- Enhance myocardial performance
- maintain reactivity of blood vessels to certain
substances (catecholamines, angiotensin II)

In hypovolemic shock, cortisol is injected along with

catecholamines….
Effect on Kidney:
- RPF, GFR
- Excretion of water

Effect on GIT:
- Gastric acid secretion
- Gastric mucosa
Effect on blood cells:
- Eosinopenia, Basopenia, Lymphopenia
- Neutrophilia, Polycythemia, Thrombocytosis
Essential during fetal life:
- Growth of CNS, Lungs, GIT, Retina, Skin etc.
- Stimulates synthesis of Pulmonary surfactant
 Therapeutic actions
Anti-inflammatory:
- Stabilize lysosomal membrane
- Inhibit Mast cell
- Inhibit migration of leukocytes
- Decrease chemical mediators of inflammation like PG,
leukotienes, thromboxanes etc.
- Inhibit fibroblastic activity
Cortisol is prescribed in chronic inflammatory
conditions…

Be cautious in using cortisol in acute infection &

inflammation….
Anti-allergic effect:

- Inhibit mast cell growth & degranulation

- Strong anti allergic action

Steroid is frequently prescribed in allergic

conditions…
Immunosuppressive action:
- Decrease circulating helper T cells
- Decrease cytokine & interleukins
- Lymphocytopenia
- Decrease macrophage formation

Cortisol is given in organ transplant patient…

Chronic cortisol use in transplant cases makes patient
prone to various infections…
 Hyper secretion of Corticosteroid
Clinical Case- Cushing’s Syndrome

Causes:
- Chronic use of Corticosteroid as drug
- Tumor of adrenal cortex
- Tumor of Pituitary (Cushing’s disease)
Characteristic features
 Characteristic features
- Central obesity (Moon face, buffalo hump)
- Purple striae: Due to stretching by excess fat
- Easy bruising
- Thin hair
- Hirsutism
- Muscle weakness (Protein catabolism)
Patient also develops….
- Osteoporosis
- Hyperglycemia
- Hypertension (increase mineralocorticoid activity)
- Peptic ulcer
- Infertility
Investigations:
- Elevated plasma cortisol
- Measure ACTH level

Treatment:
- Surgical resection of tumor
- Calibrating dose of steroid
 Hyposecretion of Adreno-cortical
hormone
Clinical Case- Addison’s disease

Causes:
- Autoimmune destruction
- TB
- Metastasis
 Characteristic features
- Weight loss
- Hyperpigmentation of skin

Low cortisol → High ACTH

ACTH mimic MSH

- Hypotension
- Hyponatremia & hyperkalemia
- Hypoglycemia

Investigation:
Low cortisol with high ACTH

Treatment: Hormone replacement therapy

 Mineralocorticoids
Aldosterone (Chief)
Deoxycorticosterone

- Zona glomerulosa
- Peak in early morning hours
 Stimulatory factors for Aldosterone
- Renin (Hypovolemia, Hypotension)
- Hyponatremia
- Hyperkalemia

- Sympathetic drive
 Actions of Aldosterone
(Lover of Sodium & Enemy of Potassium)
For Na reabsorption…..
- Number of Na channels on DCT & CD
- Permeability of tubular cell to Na+
- Na-K ATPase pump activity
- ATP production for energy
 Aldosterone Escape
Aldosterone → Na & water retention → Increase
blood volume → Increase venous return →
Secretion of ANP due to atrial stretch → Natriuresis
& diuresis → Aldosterone escape
 Hyper secretion of Aldosterone
Primary: (Conn’s syndrome) (Problem in Adrenal)
- Adrenal adenoma of Zona Glomerulosa

Patient develop…..
- Hypertension
- Muscle weakness (due to hypokalemia)
- Metabolic alkalosis
Secondary due to high renin secretion in….
- CHF
- Liver cirrhosis
- Nephrotic syndrome
- Batter syndrome (Hyperplasia of JG cells)
The Emergency Hormone
Adrenal Medulla
Hormones
Epinephrine (80%)
Norepinephrine
Dopamine

Stored as chromaffin granules in cells of adrenal medulla

 Regulation of secretion
- By sympathetic nervous system
- Via pre ganglionic sympathetic nerves from T5-T9

Helps in ‘Sympathetic alarm’ to dangerous situation

Stimulating factors are hypoglycemia, anxiety,
trauma, pain, hypovolemia, hypotension, extreme
temperature, severe exercise etc.

Secretion of E to NE ratio is 4:1

 Receptors for the Hormone
Two receptor types: α and β

α β
α1, α2 β1, β2, β3
Sensitive to both E, NE Sensitive to mainly E
Excitatory functions Inhibitory functions except
except intestinal motility myocardial excitability
 Actions of Catecholamine
Effect on Metabolic rate:
- O2 consumption
- BMR
- Heat production
 Metabolic effect of Catecholamines
Carbohydrate Lipid

+
- Hyperglycemic
-
- Lipolytic & Ketogenic
Effect on CVS:

E NE
HR (β1) First then Due to
overriding of
CO First then Baroreceptor
PR (α1) Reflex over
normal action
SBP First then
DBP
Selective effect on blood vessels:
- Vasoconstriction in Renal, splanchnic &
Cutaneous blood vessels
- Vasodilation in skeletal & hepatic blood vessels

Diverting blood volume in necessary organs &

preparing the animal for Fight or Flight reaction
Great Muscle work

Better far vision

Effect on CNS:
- Increase alertness, synaptic transmission speed

Make far vision better by

- Dilatation of Pupil
- Flat lens by relaxing cilliary muscles

Effect on RS:
Increase RR, Bronchodilatation
Effect on GIT:
- Relaxation of gut and constriction of sphincter ->
constipation

Detrusor relaxation -> Retention of urine

Piloerection & sweating

 Applied- Pheochromocytoma
Tumor of adrenal medulla

Clinical features:
Hypertension,
Tachycardia, palpitation, sweating,
Extreme anxiety,
Constipation
Hyperglycemia,
Weight loss
INSULIN- THE ONE MAN ARMY HORMONE
The only effective Hormone which decrease blood Glucose Level
Pancreatic Hormones
 Insulin
The first hormone to be isolated & synthesized
Insulin gene on chromosome 11
Β cells
Pre pro insulin Pro insulin Insulin +
C-peptide
 Regulation of Insulin

Insulin α external nutrients in diet, as insulin

stimulate utilization of these external nutrients &
inhibits utilization of endogenous nutrients
Blood Glucose level & Insulin:
At 50 mg/dl- No insulin,
100 mg/dl- Begin to release sharply,
150 mg/dl- half maximum,
300 mg/dl- maximum

Biphasic secretion
 Oral glucose stimulates more insulin then i.v.
glucose….
Due to release of GI hormones (Gastrin,
secretin, CCK, GIP) after meals, stimulate
immediate insulin release before actual
absorption of glucose.
 Role of ANS:
Emergency situation or stress →
Sympathetic stimulation → Epinephrine →
Inhibit insulin

Glucose will be available for energy

Parasympathetic → increase insulin

Mechanism of Action
1) Gene expression
2) Translocation of Glucose Transporters on
membrane
3) Enzyme activation and synthesis
(Glucokinase, PFK, pyruvate kinase etc.)
 Actions of Insulin
1) Effect on Metabolism:
Carbohydrate:
- Glucose uptake in muscle, adipose tissue, liver
mammary glands (except CNS, Kidney, vessels,
intestinal mucosa, retina, RBC)
- Glycolysis, glycogenesis
- Gluconeogenesis, glycogenolysis
Lipid:
- Lipogenesis in liver
Glucose → Glycogen → Fat
- Deposition of circulating fat in adipose
tissue by activating enzyme lipoprotein
lipase
- Inhibit lipolysis in adipose tissue, liver &
muscle
- Increase utilization of VLDL, LDL
- The only Antiketogenic Hormone
 Protein:
- Anabolic

- Growth promotion by stimulating bone

and cartilage formation
Increase uptake of K+
 Glucagon
α cells
Actions of glucagon: (More on liver)
Carbohydrate: (Opposite to insulin)
- Glycogenolysis, gluconeogenesis
Lipid:
- Lipolysis in adipose tissue, ketogenesis in liver
 Protein:
- Amino acid uptake to form glucose

Mechanism of Action:
- Adenyl cyclase- cAMP system
 Insulin- Glucagon ratio
Normal ratio is 2

Fasting, exercise → need more glucose (specially for

CNS) → ratio 0.5 or less → more glucose formed by
glycogenolysis, gluconeogenesis, lipolysis

After meal → ratio 10 or more → increase glucose uptake

and storage as glycogen, inhibit lipolysis
Applied – Diabetes mellitus
Risk factors:
- First degree relative
- Obesity
→ BMI > 30 kg/m2
→ Resistance to insulin

Metabolic syndrome
*values in mg/dl
IDDM (Type 1) NIDDM (Type 2)
Deficiency Resistance
(Autoimmune)
< 40 years (juvenile) > 40 years
10-20% 80-90%
Thin Obese
Prominent symptoms Not prominent
(Polyuria, polydipsia,
polyphagia)
IDDM (Type 1) NIDDM (Type 2)
Insulin decrease Normal or more
Ketoacidosis Not common
common
RX- Insulin RX- Hypoglycemic
drugs
 Hyperglycaemia

Glycosuria Cell dehydration Polyphagia

(180mg/dl) (Osmosis) Not able to
Polyuria Polydipsia utilize Glucose
(Osmosis) (Calorie loss)
Electrolyte loss
 Complications of Chronic DM
- Glycosylation of tissue protein leads to chronic
complications like….
Diabetic retinopathy
Diabetic neuropathy
Diabetic nephropathy
Diabetic Coagulopathy

- Hyperlipidemia & high cholesterol → Atherosclerosis

Glycosylation of protein:
HbA1c (Glycosylated hemoglobin)- addition of
glucose to Hb

Normal HbA1c level- < 6 % of total Hb

Pre diabetes- 6 to 6.5 %
Diabetes- > 6.5%
Important marker of glucose regulation in last
three months
 Ketosis
More fat utilization → increase FFA → Ketosis (Increase
ketone bodies)
Ketosis → cell dehydration & ketoacidosis (dissociation of
ketone bodies in to H+)

Features of ketoacidosis: Kussmaul’s breathing, acetone

smell, hypotension, severe acidosis, coma
 Hypoglycaemia (<40mg/dl)
Common in diabetic patients
- Overdose of drug
- Lack of food intake or mismatch
- Heavy exercise

Non-diabetic causes are hyperinsulinemia

 Clinical features:
Effect on CNS → Tremor, confusion, drowsiness,
incoordination, nervousness
Effect on CVS → Palpitation, tachycardia
Sweating, nausea, vomiting

<30 mg/dl → Hypoglycemia coma