Thyroid Physiology

Question 1

Describe the main anatomy of the thyroid

Answer 1

Right and left lobes connected via isthmus with a pyramidal lobe at top in 50% adults

Question 2

What is blood supply for thyroid?

Answer 2

Superior/inferior thyroid arteries

Superior/middle/inferior thyroid veins that drain into internal jugular

Question 3

What are two main hormones made in thyroid? Where are they made? What is their precursor?

Answer 3

T4: exclusively made in thyroid
T3: 20% made in thyroid; 80% made by extra thyroidal conversion of T4 by deiodinases

Both are synthesized from tyrosine

Question 4

Which thyroid hormone is biologically active? What is the role of the other?

Answer 4

T3 is the biologically active hormone as it has higher binding affinity for the thyroid hormone receptor.

T4 is more of a pro-hormone

Question 5

What is calcitonin? Which cells synthesize it? What is its clinical significance?

Answer 5

Calcitonin is made by parafollicular C cells in response to changes in ionized calcium.

It’s not important for physiology but is a marker in medullary thyroid cancer.

Question 6

Describe the function of thyroid hormone in following areas:
Metabolism
Lungs
Adipose/lipids
Bone

Answer 6

Thyroid increases metabolic rate, helps control respiratory muscles and increases respiratory drive, increases the number of LDL-receptors, stimulates lipolysis and activates osteoclasts/osteoblasts

Question 7

Describe the function of thyroid hormone in follow areas:
Brain
Nervous system
Heart
Blood
GI
Reproductive

Answer 7

Brain development
Increases number of ß-adrenergic receptors
Increases heart rate and contractility
Promotes increased oxygen dissociation from Hb into tissue
Promotes gut motility
Regulates ovulation and menses

Question 8

Describe role of thyroid hormone in development. When does thyroid hormone synthesis begin?

Answer 8

Thyroid hormone starts by 11 weeks gestation. It is necessary for brain development and skeletal maturation

Question 9

What occurs as a result of untreated congenital hypothyroidism? What is it called?

Answer 9

Congenital hypothyroidism, also known as cretinism causes Mental retardation and dwarfism.

Question 10

Does thyroid hormone act via genomic or non-genomic actions?

Answer 10

Both. T3 acts on nuclear receptors to mediate transcriptional regulation

T3 and T4 interact with enzymes and mitochondrial proteins

Question 11

When does thyroid receptor act as a transcriptional activator? As a repressor?

Answer 11

Depends on presence of thyroid hormone

Question 12

In HPT axis, what is the mechanism for negative feedback

Answer 12

T3 from the thyroid and extra-thyroid conversion reduces TSH output from pituitary by down regulating TRH receptors on thyrotropes.

Question 13

What are the elements of follicles? (4)

Answer 13

Iodine
Thyroglobulin
T4
T3

Question 14

What are the recommended daily intake for iodine? Describe for kids, adults, preggers and lactating women

Answer 14

Kids: 90-150
Adults: 150
Preg: 220
Lactating women: 290

Question 15

What is thyroglobulin? Where is it stored?

Answer 15

Large glycoprotein stored in vesicles and exocytosed into colloid

Question 16

Describe the first step of thyroid synthesis: Iodide transport

Answer 16

Iodide transport. Transported across basal membrane of follicular cells via Na/I symporters then transported across apical border into colloid surface via pendrin transporter (I/Cl transporter)

Question 17

Describe the second step of thyroid hormone synthesis: oxidation and organification

Answer 17

Iodide is oxidized to iodine via thyroid peroxidase (TPO) enzyme. Then Iodine is combined with tyrosine residues of thyroglobulin via TPO to form either MIT or DIT

Question 18

Describe the third step of thyroid hormone synthesis: Coupling

Answer 18

Two molecules of DIT combine to form T4 or one DIT and one MIT combine to form T3. Production of T4 is 10x faster. T4, T3 and DIT/MIT are stored in lumen as colloid. They remain bound to thyroglobulin.

Question 19

How many iodines are in T3? T4?

Answer 19

T3: 3 iodines
T4: 4 iodines

Question 20

Describe the fourth step of thyroid hormone synthesis: Proteolysis of thyroglobulin

Answer 20

When thyroid stimulated by TSH, colloid taken up in vesicles back into follicular cell

Vesicles fuse with lysosomes, which cleave T4,T3, inactive iodotyroines from thyroglobulin

Question 21

Describe the fifth step of thyroid hormone synthesis: Secretion of thyroid hormone.

What happens to unused DIT/MIT?

Answer 21

T4/T3 are transported back across basal membrane into capillaries to enter circulation.

Thyroid deiodinase cleaves unused DIT/MIT. Iodines are aded to intracellular iodine pool and leftover tyrosine are used to synthesize new thyroglobulin molecules

Question 22

How is T3 made from T4?

What is reverse T3 and how is it made?

Answer 22

Deiodinases cleave iodine from T4.

Cleavage from outer ring makes T3. Cleavage from inner ring makes reverse T3, which is biologically inactive

Question 23

How are most thyroid hormones found in blood? In what state are thyroid hormones physiologically active?

Answer 23

Over 70% of both T4/G3 are bound to thyroxine-binding globulin (TBG)

Free hormones (less than 1%) are physiologically active.

Question 24

What conditions increase TBG levels? (2) What conditions decrease TBG levels? (4)

Answer 24

TBG is increased by estrogen (OC, HRT, pregnancy) and increased hepatic release

TBG is decreased by decreased hepatic production, renal loss, congenital conditions and high levels of androgens.

Question 25

What is optimal screening test for thyroid function?

What is the relationship between TSH and T4

Answer 25

Generally look at TSH levels

There is an inverse relationship between T4 and TSH