Endocrine 09,10 - Biochemistry And Function Of Thyroid Hormone

Front 1

In the thyroid, hormones are ______ not ______.

Back 1

stored; formed on demand

Front 2

What does the thyroid follicle contain?

Back 2

Colloidal iodinated thyroglobulin.

Front 3

What hormone from the pituitary will cause thyroid enlargement?

Back 3

TSH.

Front 4

What is colloid made of?

Back 4

T3, T4, MIT, and DIT attached to Thyroglobulin.

Front 5

What ion is essential for thyroid hormone synthesis? What purpose does it serve?

Back 5

Iodide (I-).
Makes thyroid hormones more soluble.

Front 6

What are symptoms of Iodide deficiency in infants?

Back 6

Mental and growth impairment, increased infant morbidity and mortality.

Front 7

What are the 2 predominant thyroid hormones?

Back 7

1) T3 - Tri-iodothyronine
2) T4 - Thyroxine

Front 8

What is an "iodide trap"?

Back 8

Na+/I- Symporters (NIS) found on the membranes of thyroid follicles, linked to Na/K ATPase.

Front 9

What are the 3 competitive inhibitors of Na/I Symport?

Back 9

1) Thiocyanate
2) Perchlorate
3) Pertechnate
*Cause thyroid follicles to rapidly release Iodide.

Front 10

Why might a person suffering from depression also have hypothyroidism?

Back 10

Lithium therapy is common as an anti-depressant, but it is also an inhibitor of Na+/I- Symport (NIS).

Front 11

What is radioactive pertechnetate used for in the thyroid?

Back 11

To visualize thyroid anatomy and measure iodide trapping.

Front 12

How is thyroid hormone regulated at the follicular plasma membrane?

Back 12

Increase of Iodide uptake (NIS activity) will result in negative feedback for T4/T3 production and also decreased "Iodide Trapping" (NIS activity).

Front 13

What is the Wolf-Chaikoff effect?

Back 13

The plasma membrane will begin to reject excessive Iodide and slow Thyroid Hormone production (basically negative feedback).

Front 14

What hormone is released from the hypothalamus to stimulate the anterior pituitary release of thyroid hormone?

Back 14

Thyroid Releasing Hormone (TRH).

Front 15

What hormone is released from the anterior pituitary to stimulate thyroid hormone production?

Back 15

TSH after TRH binds to receptors on the pituitary gland.

Front 16

What effect does T3/T4 production have on the pituitary?

Back 16

Primary negative feedback loop, inhibit the release of TSH.

Front 17

What effect do dopamine and somatostatin have on the hypothalamus-pituitary-thyroid axis?

Back 17

Dopamine and somatostatin from the hypothalamus tonically inhibit TSH secretion from pituitary.

Front 18

TSH is a ________ glycoprotein synthesized in the ________.

Back 18

dimeric; pituitary

Front 19

Describe the pathway of T3/T4 production, beginning with TSH binding to thyroid gland receptors.

Back 19

1) Iodide is taken in via NIS
2) Thyroglobulin (TG)is produced in the ER
3) Thyroid Peroxidase produces colloidal iodinated thyroglobulin (T3-T4-MIT-DIT, bound to TG) in the follicle lumen.
4) Colloidal iodinated thyroglobulin is endocytosed and proteolysed.
5) T3/T4 is secreted with some rT3 (non-hormone)
6) MIT, DIT are recycled by Deiodinase.
7) Thyroid gland size increases.

Front 20

What is organification?

Back 20

The formation of T3-T4-MIT-DIT complex bound to TG by Thyroid Peroxidase and H2O2.

Front 21

What is Graves' Disease?

Back 21

The formation of Ab's that mimic TSH, binding to TSH receptors causing thyroid hormone hypersecretion. This results in goiter formation.

Front 22

What might cause constitutive activation of thyroid hormones?

Back 22

Hypersecreting thyroid adenomas caused by mutant TSH receptors.

Front 23

What would a defect in iodide trapping result in?

Back 23

Decreased thyroid hormone synthesis, increase in TSH.

Front 24

What would a defect in thyroid peroxidase result in?

Back 24

Decreased thyroid hormone synthesis, increase in TSH, increase in iodide trapping (no negative feedback).

Front 25

What would a defect in deiodinase result in?

Back 25

No thyroid hormone synthesis, increase in TSH, increase in iodide trapping (no negative feedback), and INCREASE in MIT/DIT excretion. Inability to recycle I- by MIT/DIT.

Front 26

What would a defect in organification/coupling result in?

Back 26

No thyroid hormone synthesis, increase in TSH, increase in iodide trapping (no negative feedback).

Front 27

Which thyroid hormone is the dominant secreted form?

Back 27

T4.

Front 28

Where is T3 formed, mostly?

Back 28

In extra-thyroid tissues where T4 is deiodinated (kidney, liver, pituitary).

Front 29

Why are transport proteins necessary for thyroid hormones?

Back 29

Because they are highly lipophilic and water insoluble.

Front 30

What are the three transport proteins of T3/T4?

Back 30

Thyroxine Binding Globulin (TBG), Thyroid-Binding Pre-Albumin (TBPA), and Albumin.

Front 31

Which transport protein is primarily responsible for thyroid hormone transport?

Back 31

Thyroxine Binding Globulin (TBG).

Front 32

How does T3 binding to its target receptor affect gene expression?

Back 32

T3 binds to its target receptors (liver, kidney, pituitary) and becomes a transcription factor that usually activates gene transcription.

Front 33

T3-bound Thyroid Receptors dimerize with ___ to form a ______ dimer that ________ ____________.

Back 33

RXR; hetero; activates; gene transcription.

Front 34

Unbound Thyroid Receptors dimerize with ___ will form a ______ dimer that ________ _____________.

Back 34

RXR; hetero; suppress; gene transcription.

Front 35

What converts T4 to T3?

Back 35

5'-deiodinase.

Front 36

How does direct T3 activity affect the mitochondria?

Back 36

Activate mitochondrial oxidative genes.

Front 37

What is the heterodimer involved in gene expression by thyroid hormone?

Back 37

TR-RXR (T3 bound or unbound)

Front 38

What is hyperthyroidism?

Back 38

Overproduction of thyroid hormone resulting in increased metabolic activity.

Front 39

What is hypothyroidism?

Back 39

Underproduction of thyroid hormone resulting in decreased metabolic activity.

Front 40

What are the similar symptoms between hyperthyroidism and hypothyroidism?

Back 40

Goiter, muscle weakness, increased infections, increase number of mitochondria in the cell.

Front 41

How does thyroid hormone affect the cardiovascular system?

Back 41

Increases cardiac output and rate.

Front 42

What developmental impairments are caused by thyroid deficit?

Back 42

Bone age, height age, and mental age are all retarded. Thyroid replacement therapy will allow "catch up" in bone and height, but not mental age.

Front 43

What is the primary cause of hyperthyroidism?

Back 43

Graves' disease.

Front 44

What are some risk factors associated with hyperthyroidism?

Back 44

Female, family history, smoking.

Front 45

What is the best way to assess hyperthyroidism?

Back 45

Clinical exam, though many hyperthyroid patients will demonstrate decreased serum TSH and increased serum T4/T3.

Front 46

What is subclinical hyperthyroidism?

Back 46

Asymptomatic, but high risk for hyperthyroidism.

Front 47

What is the best way to assess hypothyroidism?

Back 47

Measure serum TSH, also T3/T4 if necessary. Serum TSH will be high while T3/T4 levels will be low.

Front 48

What is subclinical hypothyroidism?

Back 48

Asymptomatic, but may progress to overt hypothyroidism due to a damaged or poorly functioning thyroid.