THYROID HORMONES

Dr Asma Jabeen

Learning Objectives

By the end of lecture, the students should be able to:• Describe the functional anatomy of thyroid gland• Briefly describe the mechanism of synthesis of thyroid

hormones• Discuss the functions of thyroid hormones• Explain the regulation of thyroid hormones• Describe the effects of abnormal secretion of thyroid

hormones

Thyroid Gland: Thyroid Follicles

▪ Primary hormone secreted by thyroid gland is thyroxine▪Much lesser amount is tri-iodothyronine(T3)▪ T3 has much greater biological activity(more rapidly acting,5 times potent)▪ T3 Specifically generated at sites of action by deiodination of T4

Synthesis & relaese of Thyroid hormones

Transport of thyroid hormones

• 99% of T3 and T4 combines immediately with plasmaproteins as

• Thyroxine binding globulin• Thyroxine binding prealbumin & albumin

• Slow release• Slow onset & long duration of action

Mechanism of action

What are non-genomic actions of thyroid hormones?

These are independent of gene transcription

• On Heart, pituitary and adipose tissue• Very quick effects• Regulation of ion channels/oxidative phosphorylation• May involve cAMP second messenger system

Generalized effects of thyroid hormones

➢ Calorigenic effects

➢ Sympathomimetic effects

➢ Growth promoting effects

1. Calorigenic effects:

❑ Increase metabolic activities of almost all tissues of the body → BMR increases to 60 to 100% above normal.

This is because;

▪ ↑ O2 consumption

▪ ↑ Na-K ATPase

▪ ↑ number and activity of mitochondria

❑ The rate of utilization of foods for energy is

greatly accelerated by:

▪ ↑ carbohydrate absorption from gut

▪ ↑ gluconeogenesis

▪ ↑ glycogenolysis

▪ ↑ lipolysis (increased mobilization

and metabolism of fatty acids)

T4

T3

T3TR

mRNA

Proteins for growth and

maturation

Na+, K+- ATPase MitochondriaRespiratory enzymes

O2 Consumption Metabolic rate

CO2UreaVentilation

Renal FunctionMuscle Mass

Adipose Tissue

Thermogenesis

Sweating

Insensible water loss

SubstratesO2

Cardiac Output

Ventilation

Food Intake

Mobilization of stored fat, carbohydrates and Proteins

Other enzymes, proteins

Nucleus

Cytoplasm

Whole Body Effects

(permissive)

Tissue deiodinase

Intracellular Effects

ATP use

Effects secondary to calorigenesis:

➢When the metabolic rate is increased by T3 and T4,nitrogen excretion is increased. If food intake is not increased, endogenous protein and fat stores are catabolized and weight is lost.

➢ Increased metabolic rate causes increased need for all vitamins → vitamin deficiency syndromes

2. Sympathomimetic effects:

▪ Functional synergism▪ Increased number of β- adrenergic receptors▪ Enhanced responses to circulating catecholamines▪ Treatment of thyroid storm by beta blockers

3. Effects on growth:

Thyroid hormones has both general and

specific effects on growth. Also potentiate

the effects of growth hormones on tissues.

➢ Increased responsiveness to catecholamines

➢ Most effects are on cerebral cortex and basal ganglia➢ Reaction time of stretch reflexes shortened

in hyperthyroidism

Effects on Nervous system:➢ Growth and development of brain during fetal life

and for first few years of Postnatal life.➢ Insufficient thyroid secretion by fetus →

retarded growth and maturation of brain

Specific effects of thyroid hormones

Central nervous system:

Increased responsiveness to catecholamine↓

↑ activation of RAS↓

Irritability, restlessness, inability to sleep in hyperthyroidism

(Exhausting effect on musculature- constant tirednessBut excitable effect on synapses)

Skeletal growth:

▪ Thyroid hormones promote normal growth and Skeletal development.▪ In hypothyroid growing children, growth isretarded.▪ In hyperthyroidism, excessive skeletal growth,early maturation of bones, early closure of epiphysis

Effect on skeletal muscles:

1. Slight increase in levels cause increased muscle strength but excess hormone causes protein catabolism -muscle weakness (Thyrotoxic myopathy)

2. Increased reactivity of neuronal synapses in muscle tone controlling areas of spinal cord cause FINE MUSCLE TREMORS

Effects on metabolism

▪ Carbohydrate metabolism

➢ Rapid uptake by cells

➢ Enhanced glycolysis➢ Enhanced gluconeogenesis➢ Increased absorption from GIT➢ Increased Insulin secretion

➢Effects vary with increased or decreased thyroid levels

▪ Fat metabolism:

➢ ↑ mobilization of fats from fat stores➢ ↑ free fatty acid conc. in plasma➢ ↑ oxidation of fatty acids by cellsIncreased thyroid hormone decreases the conc.of cholesterol, phospholipids and triglycerides in plasma.

Heat Production and CO2

in tissues

Peripheral vascular resistance

Diastolic Blood pressure

Reflex in Adrenergic Stimulation

Indirect

Cardiac Muscle:

◼ b-Adrenergic Receptor Density

◼ Direct effect on excitability of heart

◼ Increased heart strength by

a Myosin heavy chain isoform

Increased Na+, K+ ATPase

Ventricular contractility

and function

Direct

Cardiac Heart Rate and Contractility

Effects on cardiovascular system

Mean arterial pressure remains normal

Pulse pressure increased because of increased blood

Flow

Respiration:

Increased due to increased oxygen utilizationand CO2 formation

Gastrointestinal function:

▪ Increased secretion of digestive juices▪ Increased motility

Sexual functions:

▪ Normal hormonal level is required for normal sexual function

▪ Deficiency or excess cause abnormal function

Regulation of thyroid hormone secretion

TSH- cAMP second messenger systemTRH- Phospholipase second messenger system

Effects of TSH on thyroid gland

❑ Increased proteolysis of thyroglobulin❑ Increased activity of the iodide pump-iodide trapping❑ Increased iodination of tyrosine to form thyroid

hormone❑ Increased size and increased secretory activity of

thyroid cells❑ Increased number of thyroid cells and increased

secretory activity

Activation of cAMP second messenger system

Effect of cold & neurogenic stimuli on TRH & TSH

• Excitation of temperature regulating center of hypothalamusby cold exposure

TRH

TSH

Thyroid hormones

Increased basal metabolic rate

Antithyroid substances

1. Thiocyanate2. Propylthiouracil3. Inorganic iodides (High conc.)

❑ Thiocyanate ions decrease iodide trapping bycompetitive inhibition

❑ Propylthiouracil decreases thyroid hormone formation

• Block the peroxidase enzyme• Block coupling of iodinated tyrosines

❑Iodides in high concentration decreases all activities of thyroid gland & decreases size

Hyperthyroidism

❑ Toxic goiter

❑ Thyrotoxicosis

❑ Graves disease

Grave's disease

Exophthalmos

Diagnostic tests for hyperthyroidism

1. Basal metabolic rate BMR is +30 to +602. TSH levels are suppressed3. TSI (Thyroid stimulating immunoglobulins) are

increased

Treatment:• Thyroidectomy• Radioactive Iodine for hyperplastic gland

Hypothyroidism

• Hashimoto’s disease -Autoimmunity that destroys the gland

• Endemic colloid goiter caused by dietary Iodidedeficiency

• Idiopathic non-toxic colloid goiter- thyroiditisAbnormalities of enzyme systems

Physiological characteristics of Hypothyroidism

Myxedema

• Almost total lack of thyroid function • Excessive tissue gel in interstitial

spaces• Non-pitting edema• Atherosclerosis

Diagnostic tests for hypothyroidism

• Thyroxine levels are low• TSH levels are extremely high (in response to

test dose of TRH)• BMR is -30 to -50

Treatment

• Oral thyroxine

Cretinism

Extreme hypothyroidism during fetal life, infancy orChildhood• Failure of body growth• Mental retardation

❑ Congenital cretinismcongenital lack of thyroid gland

❑ Endemic cretinismFailure of thyroid gland toproduce thyroid hormones-genetic defect or lack of iodine

Features of cretinism

• Sluggish movements• Physical & mental retardation• More effect on skeletal growth then soft tissues so

disproportionate growth - obese, stocky, short appearance

• Tongue sometimes becomes very enlarged- obstructsswallowing & breathing- guttural breathing

Thank You