Assist prof. of Medical Physiology. It is not essential for life but essential for growth and for physical and mental well-being. Site: On both sides.

Assist prof. of Medical Physiology

It is not essential for life but essential for

growth and for physical and mental well-

being.

Site: • On both sides of the lower aspect of the

larynx and upper trachea.

Lobes: Thyroid gland is formed of 2 lobes

Gross anatomy of the thyroid gland

Histology:

• Thyroid follicle is functional

unit– A spherical structure lined

with cuboidal cells carrying microvilli (follicular cells)

– filled with ‘thyroid colloid’ containing protein called ‘thyroglobulin’.

• Parafollicular cells are present

between the follicles there are

Microscopic structure of the thyroid gland.

ThyroglobulinThyroid folliclesParafollicular

C cells

Thyroid Follicles

Thyroid gland secrete:

1. Thyroid hormones: • Thyroxin or tetraiodothyronine (T4) • Triiodothyronine (T3) • Both secreted by thyroid follicular cells

2. Calcitonin is synthesized by the Para

follicular cells• Decrease blood Ca++ level.

1. Thyroxin or T4 • Discovered first• About 90% of the thyroid output

2. T3 (Triiodothyronine) • Secreted in smaller amount

• Have shorter half life than T4

• Most active at the cellular level (3 - 5

times more active than T4)

1. Active I- uptake

2. Oxidation of I-

3. Iodination of tyrosine

4. Oxidative coupling

Blood Follicular Cell Lumen

TG

TG

TG

I-

Na+

I-

Na+

I-

I2 +

TGT3

T4

T3

T4

10 times of plasma

Active transport

Oxidation(Peroxidase)

Iodination(Peroxidase)

Coupling(Peroxidase)

Endocytosis

Proteolysis Diffusion

• Steps :• a) Active uptake of inorganic iodide

(I-)

– by an active pump. – I- is concentrated in follicular cells (> 10

times plasma level).

•Stimulated by the TSH and • inhibited by thiocyanate and perchlorate

(competitive inhibition).

Steps :

• b) Oxidation of I- to organic iodine

(I2) – By thyroid peroxidase enzyme.

• c) Iodination of tyrosine – to produce mono- and di-iodotyrosine.

d) Oxidative coupling

• Thyroxin (T4): by union of 2 diiodotyrosine

molecules.

• Triiodothyronine (T3): by union of

monoiodotyrosine with diiodotyrosine molecule.

1. Oxidation of I-, to iodine2. Iodination of tyrosine & 3. Oxidative coupling, • All require thyroid peroxidase enzyme.

• Blocked by ‘thiocarbamides’ • As thiouracil or carbimazole,

decrease T3 & T4 synthesis. • Used in treatment of

hyperthyroidism.

• Thyroid hormones present in peptide linkage with thyroglobulin protein in the colloid.

• On stimulation by TSH

– Thyroglobulin is broken by a protease

enzyme to release T3 and T4.

• 1 mg /per week (for normal thyroid hormones synthesis).

• Areas far from the sea, as the oases must be supplied with iodized table salt to prevent iodine deficiency.

• In blood most of the thyroid hormones are bound to plasma proteins.

• Normal plasma level:

– T4 level is 8 mcg/dl,

• of which 99.98% is bound and only 0.02% is free.

– T3 level is 0.15 mcg%

• and 99.8% of it is bound while 0.2% is free.

– T3 has a shorter plasma half-life (less bound)

Transport proteins are:

• a) Thyroxin Binding Globulin’ or TBG (α globulin):

– Carry about 50% of the hormones.

• b) Pre albumin (migrating ahead of albumins in

electrophoresis)

– called ‘Thyroxin Binding Prealbumin’ TBPA, or

Transthyretin.

– transports about 40%.

• c) Plasma albumin

– Carry the remaining 10%.

A. Intracellular actions (mechanism of action)B. On the whole body produce:• 1) Growth and development• 2) Energy metabolism• 3) GIT.• 4) CVS.• 5) Respiratory system.• 6) Gonads and other endocrine systems. • 7) Skeletal muscles. • 8) Vitamins and drugs.• 9) Carbohydrate metabolism.• 10) Protein metabolism.• 11) Fat metabolism. • 12) Haemopoietic system.

• T3 and T4 enter the cell by diffusion:

– a) Bind to a specific nuclear receptor

protein.

– HRC direct transcription of specific mRNA &

specific protein synthesis.

• T3 and T4 Increase:

b) number and size of mitochondria & rate of

cell respiration.

c) activity and number of cell membrane

Na+-K+ Pump.

d) amino acid transport across the cell

membrane & protein synthesis.

e) Activate proteolytic and lysosomal

enzymes especially in muscles.

•1) Growth and development: – Thyroid hormones stimulate physical,

mental and sexual growth. – Act with GH to achieve proper growth

of the body.

• a) Physical growth:

– Has a synergistic effect on GH &

potentiate the effect of somatomedins.

– development & Eruption of teeth.

– Closure of fontanels.

• b) Mental growth:

– Growth, development & function of CNS

during fetal life & 1st few years.

– Myelination of nerve fibers & development of

synapses.

• c) Sexual growth:

– Essential for maturation & fertility.

– Help milk secretion during lactation.

2) Energy metabolism:

– Stimulate

•BMR, & O2 consumption,

•heat production, and glucose uptake by cells.

– Increase Heat production by accelerating

the catabolic metabolism of cells.

– 1 mg of thyroxin increase heat

production by about 1000 calories.

3) Gastro-intestinal tract:

– Enhance glucose

absorption from the

intestine and

glycogenolysis.

– Increase appetite and GIT

motility.

4) Cardio-vascular system:

– Increase in HR and SV.

– Systolic BP is elevated,

– Diastolic BP remains normal or lowered

(VD of the peripheral arterioles → reduce PR)

5) Respiratory system:

– Increase pulmonary ventilation.

– Increase respiratory effort and increase

the rate and depth of breathing

6) Skeletal muscles:

– Required for Normal skeletal muscle

function.

– Muscle weakness occurs both in

hyper- and hypothyroidism;

– In hyperthyroidism is due to

excessive catabolism of muscle

proteins.

7) Gonads and other endocrine systems: – Normal hyroid hormones level required for

proper sexual functions. – Both hyper and hypothyroidism lead to infertility

in males and females.

– Decrease the metabolic clearance of oestogen and testosterone as they Increase the synthesis of SHBG.

– Increase metabolic clearance of glucocorticoids by the liver and increase ACTH release from the ant pituitary.

– Potentiate the action of most of other hormones.

8) Vitamins and drugs:

– Increase the synthesis of vitamin A from

carotenes in the liver.

– Stimulate the utilization and clearance of all

vitamins.

– Enhance the clearance of number of drugs

as digitalis. Vitamin A

9) Carbohydrate metabolism. – In physiologic amounts,

•Potentiate the action of insulin &– promote glycogenesis and glucose

utilization.

– In large doses, induce hyperglycemia by:

– Increase •1) the glycogenolytic effect of epinephrine,

leading to glycogen depletion.•2) gluconeogenesis.•3) intestinal glucose absorption.

10) Protein metabolism. – In physiologic amounts: have protein anabolic effect, – In large doses: increase protein catabolism.

11) Fat metabolism. – Stimulate all aspects of lipid metabolism:

• synthesis, mobilization and utilization.

– Decrease the blood level of:

• cholesterol, triglycerides, and phospholipids.

– Increase the plasma free fatty acids and glycerol.

12) Haemopoietic system.

– Stimulate erythropoiesis through

stimulation of erythropoietin

production (increase O2 carrying

capacity of the blood).

– Increase the amount of 2,3 DPG

in the RBCs.

– So, facilitate the

dissociation of O2 from Hb.

NB:

• There is (synergism) interaction between thyroid hormones and catecholamines.

• B adrenergic blockade, – is effective in decreasing cardiovascular

and CNS manifestations of hyperthyroidism.

Control of thyroid gland:

The thyroid gland activity is regulated by:

• 1. Plasma level of TSH. • 2. Thyroid stimulating immunoglobulin (TSI), • 3. Stress conditions: enhance thyroid activity • 4. Age: tends to be decrease activity with increasing age.

• 5. Pregnancy: • 6. Antithyroid agents (Goitrogens): • 7. Blood iodine level

Control of thyroid function:

1. Thyroid stimulating hormone (TSH).

• TSH has the following effects on the thyroid gland:

– a) Promote hyperplasia of the follicular cells.

– b) Increase iodide uptake of from the blood.

– c) Stimulates synthesis & release of T3 & T4.

Control of thyroid function:

1. Thyroid stimulating hormone (TSH).

• There is a negative feedback between thyroid hormones

and TSH secretion.

• Excess T3 and/or T4 suppresses the release of TSH:

– by acting on the thyrotrop cells, more than on the anterior

hypothalamus (site of release of TRH).

The feedback mechanism controlling thyroid gland activity

act mainly on the ant pituitary.

Hypothalamic control of thyroid gland.

Hypothalamus

Pituitary g.

Thyroid g.

TRH

TSH

T3 & T4

--

--

Negative feedback

2. Thyroid stimulating immunoglobulin (TSI),

– known as ‘long acting thyroid stimulator’ (LATS).

• produced by lymphocytes in all cases of Grave’s disease

(autoimmune disorder leads to hyperthyroidism).

– TSI acts on the thyroid similar to TSH

– but

– there is no –ve feed back to increased T3 and T4.

Control of thyroid function:

3. Stress conditions enhance thyroid activity:

• e.g.

– Exposure to cold

– Increase the thyroid activity:

• that increase BMR and heat production

– to

– counteract the effects of low temperature.

Control of thyroid function:

3.All types of stress

e.g exposure to cold environment stimulates the

thyroid with consequent increase in metabolic

rate and heat production to counteract the effects

of low temperature.

4. Age:

– Thyroid activity tends to decrease with increasing

age. But this effect is small.

5. Pregnancy:

– Thyroid activity increase during pregnancy.

– The placenta secretes HCG which is structurally

similar to TSH. (physiological goiter).

Control of thyroid function:

4.Age:

Although its effect is small, but there tends to

be a decrease in activity with increasing age.

5-Pregnancy

-Thyroid activity increases during pregnancy.

-The placenta secretes a hormone called ‘human

chorionic gonadotropin’ or hCG which is

structurally similar to TSH.

6. Antithyroid agents (Goitrogens):

– Primary goitrogens include thiocyanates:

• found in cabbage that inhibit I- uptake.

• Interfere with T3 and T4 synthesis.

– T4 & T3 level leads to TSH level which results

in enlargement of the thyroid gland (goiter).

Control of thyroid function:

7. Blood iodine level:

– a) Iodine deficiency: decreased T3 & T4 formation

TSH goiter.

– b) Excess iodine (Wolff– Chaikoff) results in:

• 1- Decrease in organic binding of iodine in the gland.

• 2- Inhibition of TSH effect on the gland by ↓ cAMP

response to it.

• 3- Decreased proteolysis of thyroglobulin.

Control of thyroid function:

Disorders of the thyroid gland

Disorders of the thyroid gland

1. Hypofunction (Hypothyroidism)

• may be

– Primary (thyroid defect) or

– Secondary (defect in the pituitary gland).

Manifestations vary according to the age:

– 1. Cretinism: Hypothyroidism in human infants.

– 2. Myxoedema: Hypothyroidism of human adults.

1. Cretinism

• Hypothyroidism in infants.

• May not recognized until 5-6 months after birth,

– Some thyroid hormones reach the infant through milk from his

mother.

Clinical features

a) Growth Retardation: physical , mental & sexual.

The cretin is dwarf.

b) Low BMR and O2 consumption.

Clinical features of Cretinism

c) The skin is:

– yellowish, scaly and

– scanty coarse hair, due to failure of formation of

vitamin A in the liver from carotins.

– The resulting carotinaemia gives the yellowish skin.

Clinical features of Cretinism

c) The skin: yellowish, scaly and scanty coarse hairs.

d) Facial features: – Dull, uninterested expression and puffy eye lids.

– Thick protruded tongue (macroglossia).

Infantile hypothyroidismInfantile hypothyroidism

Clinical features of Cretinisma) Growth Retardation.

b) Low BMR.

c) The skin: yellowish, scaly and scanty coarse hairs.

d) Facial features: Dull, puffy eye lids. macroglossia).

e) Abdomen is protuberant (potbelly) and

umbilical hernia.

Critinism: puffy eyelids, depressed nose, disproportionate dwarfism

Treatment

• Should be started as early as possible

– by giving thyroid hormones,

– because mental retardation, once developed, is

irreversible.

2. Myxoedema:• - Hypothyroidism in adults

Characterized by:

a) Retardation of all mental functions e.g. – lack of concentration, slow thinking, – long reflex time and sleepiness.

b) Low BMR & O2 consumption leads to:– - Weight gain.– - Increased sensitivity to cold weather.

c) Bradycardia & hypotension.

Myxoedema: puffy face, generalized fatigued appearance

d) Skin changes:

– Thick doughy Skin: due to

• deposition of myxoedematus tissue in SC.

– Pale Skin due to: • iron deficiency anaemia and

• compression of cutaneous BV by the deposited SC myxoedematus tissue.

– Yellowish due to carotinaemia.

– Cold due to decreased BMR.

– Dry scaly & brittle hair (vitamin A deficiency).

2. Myxoedema:

d) Skin changes

1- Thick Skin due to (myxoedematus tissue).

2-Skin looks pale due to iron deficiency anaemia.

3- It looks yellowish due to carotinaemia.

4- It is cold due to decreased BMR.

5- dry scaly with brittle hair due to vitamin

A deficiency.

f) Failure of sexual functions e.g.

– Impotence in the male and

– Menstrual disturbances in the female, mainly

oligomenorrhea.

e) Increased level of cholesterol & triglycerides.

Treatment by giving thyroid hormones.

2. Myxoedema:

Hyperthyroidism or

Thyrotoxicosis

II. Hyperfunction of the thyroid gland

• Hyperthyroidism or thyrotoxicosis:

Due to

– thyroid tumour or

– over stimulation of the thyroid by TSH or

TSI.

Hyperthyroidism or thyrotoxicosis

Clinical features

a) Excessive nervousness and irritability with insomnia

and tremors of hands.

b) Loss of weight inspite of Increased appetite .

– Increased catabolism of tissue proteins and oxidation of the

stored fat

c) Warm moist skin, and Fine silky hair.

Hyperthyroidism or thyrotoxicosis

Clinical features

d) Low serum cholesterol level.

e) Increased BMR and O2 consumption

– Body temp is not raised as the extra heat is lost

by excess sweating.

– Hot intolerance and prefer cold weather.

Hyperthyroidism or thyrotoxicosis

f) Ocular signs include:

• Sympathetic overstimulation.

– 1) Characteristic stare look.

– 2) Infrequent blinking.

– 3) Lid lag phenomenon.

– 4) Failure of convergence.

• 5) Exophthalmos (protrusion of eye balls) as a result of :

– ‘exophthalmos producing factor’ a degradation product of

TSH.

– accumulation of fat, water and inflammatory cells in the

retroorbital tissue and extra ocular muscles.

Ocular signs include

1-Characteristic stare due to upward retraction of

upper eye lid.

2-Lid lag phenomenon i.e a delay in the

downward movement of the upper eye lid

on following a falling object.

3-Failure of convergence.

5- Infrequent blinking.

Exophthalmos

Hyperthyroidism or thyrotoxicosis

g) Tachycardia, atrial arrythmias (as AF) and

– high systolic pressure.

– The diastolic pressure is not raised due to

peripheral VD.

– So There is high pulse pressure.

Hyperthyroidism or thyrotoxicosis

h) Rapid muscular fatigue due to reduced ATP synthesis.

i) Sexual disturbances

– Impotence in males and

– Menstrual disturbances in the female.

• polymenorrhea or

• menorrhagia

II. Manifestations of Hyperthyroidism

1) Nervousness and irritability, insomnia and tremors of hands.

2) Loss of weight inspite of Increased appetite.

3) Warm moist skin, and Fine silky hair.

4) Increased BMR and O2 consumption

5) Low serum cholesterol level.

6) Ocular signs include:– Staring look, & Infrequent blinking.– Lid lag phenomenon & Failure of convergence. – Exophthalmos

II. Manifestations of Hyperthyroidism

7) Tachycardia, arrythmias (as AF) and Systolic HTN, high

pulse pressure.

8) Rapid muscular fatigue.

9) Sexual disturbances

– In males: impotence and

– In the female: Frequent menses (polymenorrhea) and

(menorrhagia).

Goiter

Goiter

Means: enlargement of the thyroid gland. – It is accompanied by either hypo, or hyperfunction.

Causes

1. Goitrogens: – Substances that block synthesis of thyroid hormones, – e.g. thiocyanates and thiocarbamides. – They lead to T3 & T4 TSH gland size.

2. Iodine deficiency– T3 & T4 TSH goiter. – Called colloid goiter, the acini distended with colloid.

Causes of Goiter

3. Grave’s disease:– due to TSI which binds to TSH receptors on thyroid

cells diffuse goiter.

4. Nodular goiter: – Irregular enlargement of the thyroid with varying

numbers of discrete nodules, – due to exposure to stresses.

5. Physiological goiter– Sometimes noticed in adolescence and during

pregnancy.

Goiter: (enlargement of the thyroid gland)