Post on 16-Jul-2015
transcript
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
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
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
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
Thyroid Disease States
• Disease is associated with both inadequate production and overproduction of thyroid hormones.
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