Lecture 7: Thyroid and HPT Axis

Question 1

Where is the thyroid?

Answer 1

anterior to the cricoid cartilage

Question 2

Describe the morphology of the thyroid

Answer 2

2 symmetrical lobes fused by isthmus

Question 3

What is the blood supply to the thyroid?

Answer 3

superior (ext. carotid) and inferior (thyrocervical trunk) thyroid

Question 4

How is the epithelium arranged in the thyroid?

Answer 4

in follicles that contain large storage of thyroglobulin (colloid)

Question 5

Inactive, flattened follicles are __________ epithelium

Answer 5

squamous

Question 6

Once stimulated by _____, follicles become active

Answer 6

TSH

Question 7

Active follicles transform to ____________ epithelium

Answer 7

cuboidal

Question 8

The lumen of the thyroid is filled with ___________ (30% of mass)

Answer 8

colloid

Question 9

Parafollicular cells (C cells) produce ____________

Answer 9

calcitonin

Question 10

Describe the morphology of the follicular cells

Answer 10

cuboidal shape
microvilli extend into colloid
close to fenestrated capillaries

Question 11

Do the parafollicular cells touch the colloid?

Answer 11

NO

Question 12

What are the 2 precursors of thyroid hormones (or iodothyronines?)

Answer 12

1) thyroglobulin (TG)

2) iodide

Question 13

What is the bare minimum of iodide intake to avoid thyroid hormone deficiency?

Answer 13

20ug/day

Question 14

If the average iodide intake is 400ug/day and we only need 20, where does the rest go?

Answer 14

excreted into urine

Question 15

What is the Wolf-Chaikoff Effect?

Answer 15

intrathyroidal response that assures constancy of iodide storage in the face of changes in dietary iodide\

AUTOREGULATION OF IODIDE INTAKE

Question 16

Increases in iodide intake __________ (increases/decreases) gland transport and hormone synthesis

Answer 16

decrease

Question 17

What is a clinical tool to rapidly shut down thyroid hormone production in hyperthyroid patients?

Answer 17

Very high iodide doses

basically at really high doses of iodide, the thyroid does not take up a lot of it

Question 18

What are the 3 thyroid hormones?

Answer 18

1) Thyroxine (T4)
2) Triiodothyroinin (T3)
3) Reverse triiodothyronine (rT3)

Question 19

Which thyroid hormone binds to its receptor with low affinity? With high?

Answer 19

T4 –> low affinity

T3 –> high affinity

Question 20

What form of thyroid hormone is found circulating?

Answer 20

T4 (tightly bound to transport proteins in blood)

Question 21

Where is T3 found?

Answer 21

intracellularly (converted from T4)

Question 22

What is the active form of thyroid hormone?

Answer 22

T3

Question 23

What does rT3 do?

Answer 23

nothing, biologically inactive

Question 24

Which hormone has a long half life, T4 or T3?

Answer 24

T4

7-8 days

Question 25

What is the HPT axis?

Answer 25

Hypothalamus (TRH) - Pituitary (TSH) -Thyroid (T3/T4)

Question 26

Where in the hypothalamus is TRH made?

Answer 26

PVN | gets negative feedback by T4/T3

Question 27

What is the thyroid sensor in the pituitary?

Answer 27

intracellular T3 (imposes negative feedback) Type II deiodinase

Question 28

What inhibits TSH in the pituitary?

Answer 28

somatostatin, dopamine

Question 29

Describe the functional polarization of the thyroid follicle?

Answer 29

Apical: exposed to lumen (colloid) where hormone synthesis occurs; iodination of TG Basolateral: exposed to blood; iodine uptake "trap" where thyroid hormone is released

Question 30

Where are the thyroid hormones made?

Answer 30

colloid

Question 31

Where are hormones iodinized?

Answer 31

follicle

Question 32

Describe the first step of thyroid hormone synthesis

Answer 32

1) Iodide trapping: TSH stimulates iodide trapping by increasing activity of NIS co-transporter in basal membrane of follicular epithelial cell

Question 33

What carries iodide into the follicular epithelial cell?

Answer 33

NIS co-transporter | stands for sodium, iodide symporter

Question 34

Once iodide has been taken up by the cell, what is the second step in thyroid hormone synthesis?

Answer 34

2) I- is transported to the follicular lumen and oxidized by thyroid peroxidase (TPO) to form iodine (I)

Question 35

What oxidizes iodide to iodine?

Answer 35

thyroid peroxidase (TPO)

Question 36

All steps in thyroid hormone synthesis are mediated by ____

Answer 36

TSH

Question 37

What inhibits NIS? the symporter responsible for iodide uptake?

Answer 37

lithium | can be used to treat hyperthyroidism

Question 38

After iodide is transported to the apical membrane and converted to iodine, what happens?

Answer 38

tyrosyl residules on thyroglobulin are iodinated | ORGANIFICATION

Question 39

What does MIT and DIT mean?

Answer 39

``` MIT = one thyroid residue iodinated DIT = two thyroid residues iodinated ```

Question 40

What happens after iodination?

Answer 40

conjugation of iodinated tyrosines to form T4 and T3 linked thyroglobulin

Question 41

What inhibits thyroid peroxidase (TPO)?

Answer 41

carbimaxole (cannot convert iodide to iodine --> cannot iodinate hormones)

Question 42

What is the chemical make up of T4? (in terms of DIT/MIT)

Answer 42

2 DIT

Question 43

What is the chemical make up of T3?

Answer 43

1 MIT + 1 DIT

Question 44

Which hormone has the outer ring DIT and inner ring MIT?

Answer 44

rT3

Question 45

Once T3/T4 are made and iodinated, what happens?

Answer 45

endocytosis (mediated by MEGALIN) conjugated thyroglobulin with T4/T3 enters follicular epithelial cell packaged in endosomes

Question 46

What happens after endocytosis?

Answer 46

proteolyis (TG, MIT, DIT, T4, and T3 released from vesicle) then secretion into circulation

Question 47

How much thyroid hormone is stored in colloid?

Answer 47

2-3 months worth

Question 48

Which protein assists with endocytosis of conjugated thyroglobulin?

Answer 48

megalin

Question 49

What is the purpose of radioactive iodide uptake scans?

Answer 49

to measure iodide uptake in thyroid epithelial cell (via NIS)

Question 50

What do black results indicate on radioactive thyroid scan?

Answer 50

sites of uptake (hot nodule) more black area --> indicative of Graves cold nodules are more indicative of thyroid cancer than hot

Question 51

What is normal iodide uptake?

Answer 51

25% after 24 hours | dont have more because of Wolf Chaikoff

Question 52

What is iodide uptake in hyperthyroid patients? Hypothyroid patients?

Answer 52

>60% hypo:

Question 53

How do you test for an organification defect?

Answer 53

block NIS (with perchlorate) so iodide cannot be taken up should still be able to convert iodide to iodine (TPO still functional)

Question 54

Why do thyroid hormones have different effects on different tissues?

Answer 54

deiodinases

Question 55

Where are Type I deiodinases?

Answer 55

Liver, kidney, thyroid, skeletal muscle | primary source of T3 in circulation due to their OUTER and INNER ring deiodinase

Question 56

Where are Type II deiodinases?

Answer 56

brain, pituitary, placenta, cardiac muscle | outer ring deiodinase

Question 57

Where are Type III deiodinases?

Answer 57

brain, placenta, skin | inner ring deiodinase

Question 58

What percentage of T4 is deiodinated to T3?

Answer 58

80%

Question 59

What are the transport proteins for thyroid hormone?

Answer 59

1) thyroxine-binding globulin (TBG) 70% 2) Transthyretin (TTR) 10% 3) Albumin (15-25%)

Question 60

Which has a longer half life, T4 or T3?

Answer 60

T4 (7-8 days) | T3 (1 day)

Question 61

What does T4 bind to with the highest affinity?

Answer 61

TBG (but it is in lowest concentration)

Question 62

What increases TBG?

Answer 62

estrogen, hepatitis

Question 63

What decreases TBG?

Answer 63

nephrotic syndrome, steroids

Question 64

How is T4 released at target tissues?

Answer 64

cleaved by protease (reversible reaction)

Question 65

What kind of receptor is the the thyroid hormone receptor (THR)?

Answer 65

nuclear (same as steroids; forms heterodimers with retinoic acid receptor)

Question 66

Where is THR expressed?

Answer 66

nearly every cell type

Question 67

Which hormone does THR have the highest affinity for?

Answer 67

T3 (low capacity thought) | low affinity for T4

Question 68

What is the physiological function of T3?

Answer 68

1) Increase basal metabolic rate (BMR) | 2) Promote brain (CNS) maturation (increases beta-adrenergic receptors)

Question 69

How does T3 increase BMR?

Answer 69

- stimulates hepatic gluconeogenesis, proteolysis, lipolysis Increases energy/oxygen consumption; increases thermogenesis (hyperthyroid patients are heat intolerant)

Question 70

What does T3 do in terms of brain development?

Answer 70

- promotes neuronal cell migration - myelination - synaptic transmission

Question 71

What is cretinism?

Answer 71

iodine deficiency during development | short stature, mental retardation

Question 72

Why are hyperthyroid patients at risk for arrhythmias?

Answer 72

increased beta-adrenergic receptors (resting heart rate and stroke volume) T3 increases cardiac output (increases stroke volume and resting heart rate)

Question 73

Is thyroid cancer more common in women or men?

Answer 73

WOMEN (3:1)

Question 74

How do goiters form without iodine?

Answer 74

excessive production of TSH, get hyper active follicular cells causing a goiter

Question 75

Label these hyper or hypothyroid: Graves, Hashimotos thyroiditis, iodine deficiency

Answer 75

HYPER: Graves HYPO: Hashimotos thyroiditis, iodine deficiency

Question 76

What is the cause of Graves?

Answer 76

autoimmune - antibodies stimulate TSH receptor (called Long-Acting Thyroid Stimulator - LATS) leading to elevated levels of T4/T3 (thinks it is always on)

Question 77

What is Hashimotos Thyroiditis?

Answer 77

autoimmune destruction of thyroid follicles (antibodies against TPO (cannot convert iodide to iodine) and TG cold intolerance

Question 78

What is thyroid storm??

Answer 78

Hyperthyroid coupled with severe acute illness (tachycardic, altered mental status, circulatory collapse) treat with carbimazole and beta blockers (restore heart rate)