Endocrine

Dr. Adel Hussien

Assistant Prof. of Physiology
Physiology dept.-Faculty of
Medicine – Minia University
 The Thyroid gland
Learning objectives:
- Steps of formation of thyroid hormones
- Physiological effects of thyroid hormones
- Disturbances of thyroid gland function
 The Thyroid gland
- It is a butterfly shaped gland consists of
2 lobes connected by an isthmus
- It is present in front of the trachea and
below the larynx
- It is about 25gm in weight
- It is composed of follicles, each surrounds
a cavity full of colloid material (thyroglobulin)
parafollicular (C) cells lie in between the follicles lobe
Thyroid hormones: Isthmus
- T3 (triiodothyronine) &
T4 (tetraiodthyronine-thyroxin), secreted
by thyroid follicles
- Thyrocalcitonin, secreted by
parafollicular (C) cells
 Formation of thyroid hormones
Iodine requirements:
- 500 µg/day iodides are to be ingested for hormone formation
- 20% of iodides is needed for T3&T4 synthesis
- 80% of iodides is excreted by the kidney
- Iodine and thyroid hormones can be stored in the central cavity of the
thyroid follicle
Steps of thyroid hormone synthesis:
1- Colloid formation: thyroglobulin
is a glycoprotein formed by large
number of amino acid tyrosine
2- Iodide trapping (TSH controlled)
Mechanism: Na-K pump…low Na
and –ve potential inside thyroid cells
A cotransporter (secondary active
transport) carries Na+ and I-
I- is carried against conc.(1:8) and
electrical gradient (inside –ve)
Iodide trapping occurs in other organs
but not under TSH control as ,
mammary glands, sweat glands
stomach and placent
3- Oxidation of iodide to iodine
I- (iodide) peroxidase enzyme I2 (iodine)
4- Iodination of thyroglobulin
Binding of iodine to tyrosine residues
to form Monoiodotyrosine &
Diiodotyrosine (MIT&DIT)
5- Coupling (binding of tyrosine
molecules)
DIT + DIT…T4
DIT + MIT…T3
MIT + DIT…rT3(reverse T3)
T4:T3:rT3
40 : 2 : 1
rT3 blocks the action of T3
Release of thyroid hormones:
At the apex of thyroid follicular cells
endocytosis of small portions of
the colloid inside the cells that travel
towards the base of thyroid cells and
merge with lysosomes
- Liberation of T4,T3, MID,DIT from
thyroglobulin by proteinase enzyme
- Diffusion of T4,T3 to nearby capillaries
- Removal of iodine from DIT & MID by
Deiodinase enzyme
- Recycling of iodine again for
Reformation of T4 &T3
Storage of thyroid hormones: inside the thyroid follicle and the amount
stored can supply body needs for 2-3 months
 Differences between T3 and T4
T4 T3

Plasma concentration 8 µg/dl 0.15 µg/dl

Plasma protein binding great less

affinity

Onset of action After 2-3days After 6-12 hours

Maximal effect After 12 days After 2-3 days

Potency Less potent than 3-4 times more

T3 potent than T4
 Effects of Thyroid hormones
1. Effect on basal metabolic rate (BMR)
Thyroid hormone increases the metabolic activities in most of
the body tissues and increase oxygen consumption (calorigenic action).
Thyroid hormone increases the heat production in the
body, by accelerating various cellular metabolic processes
2. Effect on protein metabolism
Thyroid hormone increases the synthesis of proteins in
the cells. The protein synthesis is accelerated by the
following ways:
i. By Increasing the Transcription of DNA to RNA
ii. By Increasing the Translation of RNA
iii. By Increasing the Activity of Cellular Enzymes.
3. Effect on carbohydrate metabolism
Thyroid hormones stimulates almost all processes involved in the
metabolism of carbohydrate.
i. Increases the absorption of glucose from GI tract
ii. Enhances the glucose uptake and oxidation by the cells
iii. Increases the breakdown of glycogen into glucose
4. Effect on fat metabolism
Increase lipolysis and mobilization of body fat
Increase oxidation of fatty acids
5. Effect on body growth
Thyroid hormones are needed for physical (soft tissues and long bones),
mental and sexual growth
Thyroid hormone is essential to promote growth and development of
brain during fetal life and first few years of postnatal life.
Deficiency of thyroid hormones during this period leads to mental
retardation
6. Effect on the cardiovascular system
Thyroid hormones increases the overall activity of cardiovascular
system.
i. Increase heart rate
ii. Increase the force of myocardial contraction
iii. Increase arterial blood pressure
7. Effect on the central nervous system
Stimulation of CNS activity and function
Increased secretion of thyroid hormones, leads to excess stimulation of
the CNS. So, the person is likely to have extreme nervousness and may
develop insomnia
.
 Disturbances of Thyroid gland function
The disturbance may be hypofunction or hyperfunction
According to the site of disturbance: it may be
1- Primary (Thyroid in origin)
2- Secondary (Pituitary in origin)
3- Tertiary (Hypothalamic in origin)
 Hypothyroidism
Causes:
A- Thyroidal
1- Congenital absence of the thyroid gland
2- Defect in synthesis of thyroid hormones
3- During intrauterine life, antithyroid drugs taken by mother or excess
iodides depress thyroid gland
4- Iatrogenic cause such as,
- Excessive administration of antithyroid drugs
- Excessive removal of thyroid tissue during surgery
- Excessive destruction thyroid tissue by radioactive iodine during
treatment of hyperthyroidism
5- Chronic iodine deficiency
6- Chronic thyroiditis (inflammation): destruction of thyroid by viruses
or antibodies (autoimmiune thyroiditis)
B- Suprathyroidal
- Pituitary or - Hypothalamc
Effects of hypothyroidism:
A- General effects:
1- Decrease calorigenesis, metabolism and body temperature with cold
intolerance
2- Increased body weight due to accumulation of subcutaneous
mucoproteins and mucopolysaccharides..non pitting oedema
3- Skin is coarse and dry
4- Generalised decrease in activity of all body systems
- Cardiovascular: bradycardia & decrease COP
- Respiratory: bradypnea
- Gastrointestinal: decrease motility & constipation
5- Increase plasma cholesterol level
6- Decrease T3&T4 with increase TSH (thyroid origin)
Decrease T3&T4 with decrease TSH (pituitary or hypothalmic origin)
B- Depending on age of occurrence of hypothyroidism
1- Cretinism:
Age: in children since birth or during early childhood
Manifestations:
- Swollen eye lids with narrow palpebral fissure
- Wide nasal bridge
- Enlarged lips with enlarged protruded tongue
- Supraclavicular pad of fat
- Abdominal bulging with umbilical hernia
Delayed physical, mental and sexual development
Mentally: Idiot, unable to speak, can not control
urine or stool, very low intelligence quotient
Physically: dwarf, with delayed milestones
Delayed sitting, walking, eruption of teeth, closure of fontannels
Sexually: infantile gonads, impotent & sterile
2- Myxedema:
Age: in adults
Manifestations:
- Intolerance to cold weather
- Mental functions depressed
Apathy, drowsiness with prolonged reaction time
- Sexual functions are depressed due to slight atrophy of the gonads
- Husky voice
- Absent outer 1/3 of ye brows
 Hyperthyroidism (thyrotoxicosis)
Causes:
1- Thyroid over activity: high T3&T4 with low TSH
- Grave’s disease: auto antibodies are formed against the thyroid gland
TSH receptors (TSH-receptor-stimulating antibodies) also named
long acting thyroid stimulator (LATS), TSH receptors are stimulated
by these antibodies
- Acute thyroiditis
- Thyroid tumors
2- Suprathyroid over activity: high T3&T4 with high TSH
- Pituitary tumor
- Resistance of pituitary to negative feedback control by thyroid
hormones due to genetic mutation
3- Extrathyroidal activity: high T3&T4 with low TSH
- Ectopic thyroid tissue producing excessive amounts of T3&T4
- Excessive intake of thyroid hormones
Manifestations:
- Increase body metabolism…warm, flushed,
sweaty skin (the patient can not tolerate
hot weather)
- Loss of body weight: inspite of increased
Appetite (due to increased metabolism)
- CNS: patient is nervous, irritable, with fine
Tremors in the extended abducted fingers
- CVS:
Increased heart rate (tachycardia) with increased COP explain why?
ABP, increased systolic blood pressure with decreased diastolic blood
pressure…increased pulse pressure
- Eyes: Exophthalmos (protrusion of eye ball)
Occurs due to excessive accumulation of retro-orbital tissues due to
over stimulation by LATS antibodies, blindness may occur
 Goiter
Enlargement of the thyroid gland
Types:
1- Physiological: during puberty and
pregnancy due to meet the body needs
For increased metabolism
2- Hypothyroidism: most commonly due
to iodine deficiency (endemic goiter)
3- Hyperthyroidism due to thyroid or pituitary tumors, or Grave’s
disease
4- Nodular goiter: multiple enlarged thyroid nodules may be hot
(active) or cold (inactive)