Thyroid gland

Question 1

What is the functional unit of the thyroid gland?

Answer 1

Thyroid follicle
-surrounded by epithelial follicular cells and parafollicular cells (that secrete calcitonin in response to increased Ca), filled with colloid

Question 2

How much thyroid hormone is secreted per day?

Answer 2

60 ug/day

-the body can hypothetically last 2-3 months with the amount stored in the Thyroid gland

Question 3

Why is more T4 produced than T3?

Answer 3

10x faster reaction speed

Question 4

Why is T4 peripherally converted to T3? How does this occur?

Answer 4

T3 is the major active hormone, occurs with a deiodinase (type 1 in periphery[80-90%] and type 2 in CNS)

Question 5

What does “I trap” refer to?

Answer 5

The Na+/I- symporter that actively transports I- into the follicular cell. Stimulated by low I- levels in the body

Question 6

What are the competitive inhibitors to I-trap?

Answer 6

Thiocyanate and perchlorate

Question 7

How does I- get to the colloid?

Answer 7

Through pendrin (channel that allows I2 out in conjunction with Cl-) after I- is converted to I2 by thyroid peroxidase

Question 8

What does peroxidase do?

Answer 8

1. Oxidizes I- to I2
2. Organification of I2 into thyroglobulin
3. Coupling reactions (MIT+DIT or DITx2)

Question 9

What inhibits thyroid peroxidase? and what can it treat?

Answer 9

Propylthiouracil (PTU) at all three steps

PTU can be a good treatment for hyperthyroidism

Question 10

What is the Wolff-Chaikoff effect?

Answer 10

High levels of I- that inhibit organification and synthesis of thyroid hormone

Question 11

How do T3/T4 get out of the colloid when the thyroid gland is stimulated?

Answer 11

Iodinated thyroglobulin is endocytosed into follicular cell. T4 and T3 are then hydrolyzed via lysosomal proteases and transported across the basal membrane to nearby capillaries

Question 12

What happens to the leftover thyroglobulin/MIT/DIT once inside the follicular cell?

Answer 12

MIT and DIT are deiodinated via thyroid deiodinase to recycle the iodide and tyrosine molecules

Question 13

What is pendred syndrome?

Answer 13

When pendrin pump not working thyroid hormone synthesis is affected = hypothyroidism. Cochlea also affected = sensorineural hearing loss.

Question 14

What are the main thyroid hormone binding proteins?

Answer 14

Thyroxine-binding globulin (TBG) - higher affinity for T4
Transthyretin (TTR) - in brain
Albumin

Most circulating TH is T4–1/2 life of 6 days compared to T3’s 1 day

Question 15

What is the T3 resin uptake test?

Answer 15

Can indirectly assess circulating levels of TBG. TBG has multiple binding spots for T3/T4. Add unbound and labeled T3 to solution and let it bind to unbound TBG sites. Measure T3 uptake which tells how much of the labeled T3 did not bind to TBG

Question 16

What does high T3 uptake in the resin test mean?

Answer 16

Hyperthyroidism: high T4 so more bound to TBG = less spots for T3 binding

Question 17

What does low T3 uptake in the resin test mean?

Answer 17

Hypothyroidism: low T4 so more T3 bound to TBG = less uptake

Question 18

Where is TBG synthesized?

Answer 18

In the liver

Question 19

What happens to TBG and T3/T4 levels during liver failure?

Answer 19

Low TBG synthesis (since it’s made in liver) = transient increase in free T3/T4 levels = negative feedback to thyroid = decreased T3/T4 synthesis

Question 20

What happens to TBG levels during pregnancy?

Answer 20

They are increased because high estrogen is a modulator in liver for binding protein formation.

Question 21

What does it mean if a patient is ‘clinically euthyroid’?

Answer 21

During pregnancy there is an increase in TBG = increased levels of bound T3/T4 causes increase secretion of T3/T4. Levels of free T3/T4 still normal though

Question 22

What is TSH secretion like compared to GH secretion?

Answer 22

Steady rate rather than pulsatile

Question 23

What is the second messenger for TSH?

Answer 23

cAMP

Question 24

What are the two actions for TSH on the thyroid gland?

Answer 24

Increase synthesis/secretion of thyroid hormones and trophic effect on thyroid gland (growth)

Question 25

What are some of the actions of thyroid hormones?

Answer 25

Growth, bone maturation, maturation of CNS (more dendrites and synapses), increase in Na-K ATPases, increase heat production and BMR, increased O2 consumption, increased glucose absorption, increased lypolysis, increased cardiac output -also direct the formation of beta1-adrenergic receptors, lysosomal enzymes, transport and structural proteins to perform the actions

Question 26

How do thyroid hormones increase BMR?

Answer 26

Due to increased activity of Na-K ATPase (increased O2 consumption and heat production)

Question 27

What can deficiency of thyroid hormones during perinatal period lead to?

Answer 27

Congenital hypothyroidism leading to abnormal development of synapses and decreased dendritic branching and myelination

Question 28

What is Hashimoto's thyroiditis?

Answer 28

The most common cause of hypothyroidism in iodine-sufficient areas, caused by autoimmune gland destruction by anti-thyroid antibody. High TSH levels and low T3/T4.

Question 29

Why can patients with Hashimoto's thyroiditis have a goiter?

Answer 29

Low T3/T4 levels increase TSH secreted by pituitary which has a trophic effect on the thyroid gland

Question 30

What is Sheehan syndrome?

Answer 30

Postpartum hypopituitarism due to necrosis of pituitary gland - women present w/ the inability to produce milk, lactate, or menstruate - can have hypothyroidism and other endocrine issues

Question 31

What are a few of the reasons T4 might not be converted to T3 clinically?

Answer 31

- body is Fasting - increased stress (could be due to surgery) - certain Catabolic diseases

Question 32

What would a mutated Pendrin gene result in?

Answer 32

Faulty transport across the apical membrane (I- being converted to I2 moving across) Also affects the cochlea---sensorineural hearing losses Predred Syndrome patients present with hypothyroidism w/ goiter

Question 33

Why is the effect of Thyroid hormones on Lipid metabolism important?

Answer 33

They stimulate fat mobilization-->plasma [fatty acids]^ -the conversion of carotene to vitamin A relies on this mechanism ([cholesterol and Triglycerides] in plasma inversely proportional to TH) Patients with Hypothyroidism can suffer from blindness and yellowing skin due to the increased [cholesterol] in the blood

Question 34

What is the politically correct term for Cretinism, and how does that occur?

Answer 34

Congenital Hypothyroidism -Deficiency of Thyroid hormone during the perinatal period (22 weeks-about 1 week post-birth) causes neural changes condition of severely stunted physical and mental growth

Question 35

Would TSH levels be increased or decreased in Grave's disease? why? What is the big difference in secondary hyperthyroidism?

Answer 35

Decreased...the Thyroid Hormone levels are raised in circulation, causing negative feedback inhibition of TSH secretion Secondary- involves defects in the hypothalamus or pituitary (TSH secreting tumor) -if something is wrong with the Anterior pituitary, TSH will be increased

Question 36

What might an iodine deficiency cause? (thyroid-wise)

Answer 36

Hypothyroidism--- leads to transient decrease in TH, which of course leads to more TSH secretion, naturally presenting with a goiter -"euthyroid" and assymptomatic if the glands are able to maintain a normal level of thyroid hormones