Thyroid DSA by Objectives

Question 1

1. Define thyroxine and triiodothyronine.

Answer 1

Thyroid hormone is comprised of two hormones, thyroxine or T4 and triiodothyronine or T3. The functions of the two hormones are similar but the action and affinity of T3 for the thyroid hormone receptor is greater, resulting in a higher activity than T4. T4 is converted to T3 in tissues through the action of deiodinases

Question 2

2. Describe the regulatory pathway for thyroid hormone synthesis including negative feedback signals.

Answer 2

TRH stimulates TSH release from the anterior pituitary, which stimulates thyroid cells to produce thyroid hormone.
Free T3 downregulates the TRH receptor

TSH activates adenylyl cyclase –> cAMP. Stimulates every step of the pathway, plus a trophic effect

Thyroid stimulating immunoglobulins mimic TSH effect by binding to TSH receptors (in Graves Disease these antibodies are highly increased)

stimulatory factors:
TSH
Thyroid-stimulating immunoglobulins
Increased TBG levels (e.g., pregnancy

Inhibitory factors:
I − deficiency
Deiodinase deficiency
Excessive I − intake (Wolff-Chaikoff effect)
Perchlorate; thiocyanate (inhibit Na + -I − cotransport)
Propylthiouracil (inhibits peroxidase enzyme)
Decreased TBG levels (e.g., liver disease)

Question 3

3. Describe the steps and cellular location for thyroid hormone biosynthesis.

Answer 3

1. Thyroglobulin synthesized on the RER and Golgi apparatus of thyroid follicular cells
2. Na+/ I cotransporter brings in iodine, which is necessary for thyroid hormone synthesis (I-trap)
3. Oxidation of I- to I2
4. Organification of I2. (High levels of I- inhibit organification of I2) –> MIT and DIT
5. Coupling of MIT and DIT –> T3 and T4 contained in thyroglobulin
6. Endocytosis of thyroglobulin into follicular cells
7. Hydrolysis of T4 and T3 from thyroglobulin
8. Deiodination of MIT and DIT

Question 4

4. Understand the transport of T3 and T4, and explain the importance of thyroid hormone binding in blood for free and total thyroid hormone levels

Answer 4

T3 is the active form. Much more T4 is produced; it is activated in target tissues.

Thyroid hormone circulates in bound (to Thyroxine Binding Globulin) or free form. Because only free thyroid hormones are physiologically active, the role of TBG is to provide a large reservoir of circulating thyroid hormones, which can be released and added to the pool of free hormone.

Question 5

5. Propose the clinical relevance of conversion of T4 to T3 and rT3(deiodination) in peripheral tissues (p. 909 paragraph 3, p. 910 “Thyroid hormones have slow onset and long duration of action”).

Answer 5

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Question 6

6. Describe the metabolic actions of thyroid hormone.

Answer 6

Thyroid hormones act synergistically with growth hormone and somatomedins to promote bone formation; they increase basal metabolic rate (BMR), heat production, and oxygen consumption; and they alter the cardiovascular and respiratory systems to increase blood flow and oxygen delivery to the tissues.