PHYSIOLOGY THYROID HORMONE

by

Karishma R. Pandey

Dept. of Basic and Clinical Physiology

OBJECTIVES

1. Introduction-an anatomical consideration2. Bio-synthesis and Secretion of thyroid hormone

3. Transport4. Activation and degradation at target organ

5. Physiological activities at target organs

6. Control/ regulation of thyroid hormone

7. Pathophysiology & pharmacology-A snapshot8. Tests of thyroid function

Introduction

Uniqueness

• Easily seen and palpated

• Iodine

• Stored in an extracellular site

• Peptide hormones - no cell-membrane receptors

• Nuclear receptors.

Bio-synthesis and Secretion of Thyroid Hormone

1. Iodide Transport2. Thyroglobulin

Synthesis3. Oxidation o f

Iodide4. Organification

(lodination)5. Coupling6. Storage7. Secretion

Structures of Thyroid Hormone

Secretion of thyroid hormone

ALB

T4,T3

TRANSTHYRETIN

T4,T3

TBG T4,T3,rT3

Transport of thyroid hormones

T4 T3

Total conc. in plasma

8 µg/dl 0.15 µg/dl

% of bound form

99.98% 99.8%

Free form 2 ng/dl 0.3 ng/dl

% of free form 0.02% 0.2%

Biological half-life

Long (6-7days)Shorter average 2

days

Thyroxine (T4)

T3 rT3

Thyronine

Deiodinase

1 & 2

Deiodinase 3

DeiodinaseDeiodinase

Thyroxine Catabolism

DIT

MIT

Deiodinase

Conjugated in liver

Hydrolysed/

reabsorbed/

excreted

Action at target organ

Mechanism of T3

4 functional intranuclear T3 receptors: α1, α2, β1 and β 2;

nonfunctional receptor: α2.

The different forms of thyroid receptors have patterns of expression that vary by tissue and by developmental stage.

The presence of multiple forms of the thyroid hormone receptor, with

tissue and stage-dependent differences in their expression, suggests

an extraordinary level of complexity in the physiologic effects of

thyroid hormone.

1. Effect of thyroid hormones on BMR

• Extreme excess of thyroid secretion increases BMR to 60-100% above normal

• Complete lack of thyroid secretion causes BMR to fall 40-50% below normal

Mechanism of increasing metabolic rate and temperature

by increasing number, size and activity of mitochondria By increasing plasma membrane Na+-K+ ATPase ActivityBy stimulating both catabolic and anabolic reactions in pathways affecting fats ,carbohydrates, and proteins

Effects secondary to increased metabolism

Increased O2 consumption in almost all the cells exceptions are the adult brain,testes,uterus,lymph nodes,spleen,and anterior pituitary.

Nitrogen excretion is increased

Weight loss due to catabolism of endogenous protein and fat stores

Increased urinary excretion of K+, uric acid

Precipitation of vitamin deficiency syndrome due to increased need for vitamins resulting from increased metabolic rate

Control and regulation of thyroid hormones

Thyroid Disease States

• Disease is associated with both inadequate production and overproduction of thyroid hormones.

Hyperthyroidism

Effects and symptoms

Effects and symptoms

Hypothyroidism

Sick Euthyroid Syndrome

The relative activity of the deiodinase changes in response to physiological and pathological stimuli

The decrease in T3 production with fasting is an important adaptive response, increase in rT3 and normal TSH

Non thyroidal illness• Burns • Trauma, advanced cancers,• Cirrhosis• Renal failure.• Fasting• Glucocorticoids• Fetus• Certain drugs

Thyroid Function Tests

TSH

FT4, (T4)

T3, FT3

Thyroid stimulating immunoglobulin (TSI) or TSHR antibody

Antithyroid peroxidase antibodies (Anti TPO)

Thioamides:

propylthiouracil,

Methimazole,

Carbimazole

Thiocyanate (SCN– )

Perchlorate (ClO4– ),

Site of Action of Different Antithyroid Agents

Thank you