Lecture 7-thyroid Flashcards
Contrast the mechanism of action between TSH & TRH
TRH- increases IP3 & DAG, which increases Ca2+
This leads to release of TSH via exocytosis
TSH-leads to Gs protein activation—> Adenylyl cyclase stimulation—> increased cAMP and PLC
This leads to stimulation of thyroid hormone synthesis and tropic effect on the thyroid gland
Where is TRH synthesized?
A tripe o tide, synthesized in PVN
How is TRH secreted?
Secreted at a constant or tonic rate. Half life 9f about 5 minutes
State the type of hormone that TSH is?
Large glycoprotein
What is the half life of TSH?
About 30 minutes
What are the functions of TSH?
Stimulates all steps of thyroid hormone synthesis.
• Promotes growth of the thyroid gland. Prolonged stimulation of TSH causes
Enlargement of the thyroid aka goiter.
Where are the receptors for TSH? What is the clinical significance of this?
TSH-R is located on the basolateral side of the membrane
• TSH – R receptor is a target for autoantibodies - stimulatory as in Graves disease
- blocking as in Hashimoto’s disease
What are the major products synthesized by the thyroid gland?
Major products are:
➢ Thyroxine (T4) – 90%
➢ Triiodothyronine (T3) – 9%
➢ Reverse T3 (rT3) - 1 %
➢ Triiodothyronine (T3) has the major physiological actions – more potent
Note: T4 is broken down to T3 mainly in liver and kidneys (5` - deiodinase). 55% is rT3 and so has no metabolic effects
Describe the importance of iodine
Synthesis of thyroid hormones
requires iodine
• Daily requirements are 150μg obtained from the diet.
• Is ingested in form of iodide (I-) or iodate (IO3)
-Pregnant women & lactating
females
have higher iodine requirements
• Deficiency in the diet will decrease the amounts of hormone produced
What happens to iodine ingested each day?
Iodine ingested each day (500μg)—> ECF iodine (150 ug)—> thyroid gland (8000 ug)—> circulating thyroid hormones(600 ug)—> liver (processor)—> ECF iodine (150 ug)
ECF iodine (150 ug)—> urine (485 ug)
What is the main step in thyroid hormone synthesis?
Made from iodine ti on of tyrosine molecules grouped together in thyroglobulin
Describe the structure of thyroglobulin
Large glycoprotein
Contains ~ 70 tyrosine molecules
Made in epithelial cells
How is thyroglobulin made?
Made in epithelial cells
– Synthesized in ribosomes
– Transport to Golgi Apparatus – Discharged into follicle lumen
Synthesis and storage of TH remains here
What do Perchlorate and thiocyanate inhibit?
Na+, I- cotransport at the basal membrane
What are the steps involved in the synthesis of thyroid hormones in thyroid follicular cells?
- Synthesis of TG; extrusion into follicular lumen
- Na+-I- cotransport at the basal membrane
- Oxidation of I- to I2 at the Apical (luminal membrane) (requires peroxidase, inhibited by PTU)
- Organification of I2 into MIT + DIT at the Apical membrane( luminal membrane) (requires peroxidase, inhibited by PTU)
- Coupling reaction of MIT and DIT into T3 and T4 (luminal membrane) (requires peroxidase, inhibited by PTU)
- Exocytosis of TH at the Apical membrane
- Hydrolysis of T4 and T3; T4 and T3 enter circulation via lysosomes( require proteases)
- Deiodination of residual MIT and DIT. Recycling of I- and tyrosine intracellularly-requires enzyme deiodinase
What are the stimulators factors of thyroid hormone secretion ?
TSH
Thyroid stimulating immunoglobins
Increased TBG levels (e.g., pregnancy)
What are the inhibitory factors affecting thyroid hormone secretion?
I- deficiency
Deiodinase deficiency
Excessive I- intake (Wolff-Chaikoff effect)
Perchlorate; thiocyanate (inhibit Na+-I- cotransport)
Propylthiouracil (inhibits peroxidase enzyme)
Decreased TBG levels (e.g., liver disease)
What are the intracellular effects of thyroid hormones?
- increased mitochondria
- increased respiratory enzymes
- increased Na+-KATPase
- Other enzymes which increase oxygen consumption + increased metabolic rate
How does thyroid hormones affect o4gans on a large scale?
Assures normal bone and brain growth and development
Increased ventilation and CO2 released
Increased cardiac output
Increased urea and renal function
What are the whole body effects of thyroid hormones?
↑BASAL METABOLIC RATE (BMR), body temp. & O2 consumption
➢ T4 and T3 increase the O2 consumption of almost all metabolically active tissues.
➢ A significant proportion of
O2 is used to increase the expression and the activity of Na+-K+ ATPase
What are the cardiac effects of thyroid hormones?
Increased SR Ca2+ ATPase
Increased Na+ -K+ ATPase
Increased B1 adrenoreceptors
Increased SV + increased HR= increased CO
Increased BMR —> vasodilation—> increased blood flow
What are the metabolic effects of thyroid hormones ?
- ↑’s glucose absorption from GIT
- ↑’s use of glucose, fats and proteins for energy use (oxidation)
- ↑ the effects of other hormones that themselves increase metabolic rate
- ↓ body weight if not eating right to fulfill the increased BMR demand
What are the effects of thyroid hormones on growth?
- Stimulates of bone. Act synergistically with somatomedin to promote bone formation
- Stimulates somatomedin production in the cartilage growth plate
-Regulates development & important for
function
-Very important in the growth & development of the fetus and during
early infancy
What do thyroid hormones do to the general cell?
Adipose cells-lipolysis
Liver, uptake of fatty acids glycerol is used to release glucose from the liver
Protein is broken down in muscle, amino acids sent to liver for liver to release glucose
How are thyroid hormones transported?
70% of T3 and T4 bound to
-thyroxine binding globulin
• Rest bound to albumin,
lipoproteins and transthyretin
• Maintains an adequate reserve of thyroid hormone (mainly T4).
- Prevents loss via excretion in urine.
- pregnancy & estrogen increase levels of TBG
- Liver disease will decrease TBG levels
What is hyperthyroidism?
•increased levels o TH in the blood – Thyroid Enlargement (Graves Disease) -overactive lump – Toxic multinodular goitre
What is Graves’ disease?
- Most common (1% of population)
- Autoimmune disease
- Females 3-5x more likely
- Due to an antibody (TSH-R-Ab [stim]) that increases growth and function of the thyroid
What are the symptoms of hyperthyroidism ?
Nervousness irritability
Hyperphagia
CHF in elderly
Warm, soft skin
Heat intolerance, sweating
Increased bowel movements
Palpitations
Amenorrhea
Fine tremor of fingers
Weight loss
Occurrence of swelling of tissues in the orbits, producing protrusion of the eyeballs (exophthalmos) in Graves’ disease
What are the causes of primary hyperthyroidism?
Primarily due to low levels of TH in blood
❖Hashimoto’s thyroiditis
❖ Thyroidectomy
❖Iodide deficiency (Endemic Goiter)
Secondary ❖ Insufficient pituitary action ❖ Resistance of organs to TH
What are the effects of hyperthyroidism in adults?
- Fatigue & Cold intolerance
- Weight gain
- Menstrual problems
- Slow deep tendon reflexes, usually slow relaxation phase
- Coarse dry skin
- Bradycardia, Constipation
- If severe they develop myxedema due to accumulation of glycosaminoglycans (GAGs) mainly hyaluronic acid
- This is observed as puffiness
What can cause hyperthyroidism in newborns?
May be due to:
- Iodine deficiency
- Placental transfer of TSH Ab’s
What are the symptoms of hyperthyroidism in newborns?
Symptoms
– Respiratoryproblems, jaundice, poor feeding, umbilical hernia, reduction of bone development
What are the symptoms of hyperthyroidism in children?
Growth retardation (dwarfism) Mental retardation (cretinism)
