Thyroid and HPT Axis

Question 1

What is the blood supply of the thyroid?

Answer 1

Superior and Inferior Thyroid Arteries

Question 2

What is the cell type found in inactive follicles?

Answer 2

Squamous Epithelium

Question 3

What is the cell type found in active follicles?

Answer 3

Cuboidal Epithelium

Question 4

What is the follicle?

Answer 4

Epithelial cells surrounding lumen - lumen filled with colloid

Question 5

What is the function of the C cells (parafollicular cells)?

Answer 5

Produce calcitonin and maintain the follicle

Question 6

What are the 2 precursors of thyroid hormone?

Answer 6

Thyroglobulin (TG) and Iodide

Question 7

What is the Wolf-Chaikoff effect?

Answer 7

Increases in iodide intake decrease gland transport and hormone synthesis and vice- versa.

Allows for constant iodine storage even with dietary changes.

Question 8

How is the Wolf-Chaikoff effect used clinically?

Answer 8

Very high iodide doses are used to rapidly shut down thyroid hormone production in hyperthyroid patients

Question 9

What are the different thyroid hormones?

Answer 9

T3
T4
rT3

Question 10

What is T4?

Answer 10

Thyroxine.

Tightly bound to transport proteins in blood Binds to receptor with low affinity

Question 11

What is T3?

Answer 11

Triiodothyronine.

Primary active form
Binds with high affinity, low capacity to receptor

Question 12

What is rT3?

Answer 12

Reverse Triiodothyronine.

Inactive

Question 13

What are the components of the HPT axis?

Answer 13

Hypothalamus - PVN
Pituitary - Thyrotropes
Thyroid

Question 14

How is the HPT axis regulated?

Answer 14

Negative feedback by T4/T3 in hypothalamus.

Negative feedback in pituitary by intracellular T3

Question 15

What does the polarization of the thyroid follicle refer to?

Answer 15

Different functions of the apical and basolateral membranes

Question 16

What is the function of the apical follicle?

Answer 16

Apical surface is exposed to the lumen (colloid) and thyroid hormone synthesis occurs here with the iodination of TG

Question 17

What is the function of the basolateral follicle?

Answer 17

Basolateral surface is exposed to the blood and is responsible for the uptake of iodine and the release of thyroid hormone

Question 18

What occurs with iodide trapping?

Answer 18

TSH stimulates iodide (I-) trapping by increasing the activity of the NIS (sodium iodide symporter) co- transporter in the basal membrane of the follicular epithelial cell.

Question 19

What happens after iodide transported into the follicle?

Answer 19

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

Question 20

What is iodination?

Answer 20

Tyrosyl residues on TG will have iodine added to them

Question 21

What is the conjugation of iodinated tyrosines?

Answer 21

Conjugation of iodinated tyrosines to form T4 and T3-linked thyroglobulin (TG)

Question 22

What is the function of the drug carbimazole?

Answer 22

Inhibits thyroid peroxidase.

Iodide will not be oxidized into iodine.

Question 23

What happens of following conjugation of iodinated tyrosine?

Answer 23

• Conjugated thyroglobulin with T4/T3 enters follicular epithelial cell.
• Packaged in endosomes
• TG, MIT, DIT, T4, T3 released from vesicle
• T4/T3 secreted into circulation

Question 24

What is the function of the radioactive iodide uptake scan?

Answer 24

Measures iodide uptake and used to determine function of thyroid gland.

Normal is 25% in 24 hours
> 60% = hyperthyroid

Question 25

What is the function of Type I thyroid hormone conversion?

Answer 25

Outer and inner ring deiodinase Liver, kidney, thyroid, skeletal muscle Primary source of T3 in circulation

Question 26

What is the function of Type II thyroid hormone conversion?

Answer 26

Outer ring deiodinase Brain, pituitary, placenta, cardiac muscle

Question 27

What is the function of Type III thyroid hormone conversion?

Answer 27

Inner ring deiodinase Brain, placenta, skin

Question 28

What are the transport proteins for thyroid hormone?

Answer 28

Thyroxine-binding globulin Transthyretin Albumin

Question 29

What thyroid hormone is the most tightly bound in circulation?

Answer 29

T4

Question 30

What is the thyroid hormone receptor?

Answer 30

Nuclear receptor family - same as steroid hormones - forms heterodimers with - retinoic acid receptor (RXR)

Question 31

What is the receptor affinity of thyroid hormone receptor for T3 and T4?

Answer 31

High affinity, low capacity for T3 Low affinity for T4 – very little biological activity at physiological concentrations

Question 32

What are the functions of thyroid hormone?

Answer 32

Increases BMR (Stimulates hepatic gluconeogenesis/proteolysis/lipolysis) Promotes CNS maturation Increases beta-adrenergic receptors Increases thermogenesis

Question 33

What is the cause of cretinism?

Answer 33

T3 is crucial for normal brain development Cretinism is caused by iodine deficiency during development

Question 34

What are the effects of cretinism?

Answer 34

Short stature/impaired bone formation Mental retardation | Delayed motor development

Question 35

What is the effect of thyroid hormone on the heart?

Answer 35

T3 increases cardiac output

Question 36

Why are goiters formed in hyper and hypothyroidism?

Answer 36

Hyper - thyroid overstimulation Hypo - no negative feedback on thyroid which will increase TSH levels and form goiter

Question 37

What is the cause of Graves Disease?

Answer 37

Autoimmune – antibodies stimulate TSH receptor (Long Acting-Thyroid Stimulator – LATS) which lead to increased T3/T4

Question 38

What are some symptoms of Graves Disease?

Answer 38

Diffuse symmetrical goiters with hyperthyroid symptoms: tachycardia, opthalmopathy, irritability, hyperactivity, heat intolerance, weight loss, nervousness, muscle wasting

Question 39

What is the cause of Hashimoto's Disease?

Answer 39

Autoimmune destruction of thyroid follicles that will destroy TPO and TG which causes hypothyroidism

Question 40

What are some symptoms of Hashimoto's Disease?

Answer 40

Diffuse goiter with hypothyroid symptoms: lethargy, fatigue, hair loss, cold intolerance, brittle nails decreased appetite, weight gain

Question 41

What is the cause of thyroid storm?

Answer 41

Hyperthyroid disorder coupled with severe acute illness

Question 42

What are the symptoms of thyroid storm?

Answer 42

``` High fever Tachycardia Altered mental status Severe nausea, vomiting, diarrhea Severe circulatory collapse ----- resulting in death ```

Question 43

What is the function of thyroid peroxidase (TPO)?

Answer 43

Converts iodide into iodine