3. The thyroid gland: Control of secretion, effects of the thyroid hormones

Question 1

Development of the thyroid?

Answer 1

• Thyroid tissue arises in the midline at a point on the tongue later known as the foramen caecum
• Epithelial cells sink downwards anterior to the hyoid and larynx (week 7)

Thyroglossal duct connects the developing thyroid to the tongue

Question 2

What is the hypo-pituitary control of the thyroid hormone release?

Answer 2

Small-boided neurones in the arcuate nucleus and median eminence synthesise and secrete thryotropin-releasing hormone (TRH)
Long portal vessels carry RH to the ant pituitary.

Question 3

Feedback inhibition of TH release

Answer 3

T3 and T4 from thyroid feedback to:

• -> Ant pituitary. Inhibit thyrotroph activation, decrease TSH release
• –>Arcuate nucleus of hypothalamus: Inhibit TRH release

Dopamine also inhibits ant pit

Question 4

Structure of thyroid hormones

Answer 4

T4 = Thyroxine

T3 = Triiodothyronine

Both made up of:

• Hydroxyl group
• A ring (With iodine bonded)
• Ester bond
• B ring (With iodine bonded)
• Methyl group
• Amine
• Acid group

Question 5

Synthesis and secretion of T3 and T4

Answer 5

1. TRAPPING
   TSH increases the activity pf a Na/I co-transporter (NIS) on the basolateral membrane of the thyroid follicular cell. The result is increased iodine trapping i.e. the ratio of follicular-cell iodine to plasma iodine increased under conditions of high TSH
2. Iodine leaves the cell, probably via pendrin and enters the lumen. The follicular cell also secretes thyroglobulin. Thyroid peroxidase (on luminal surface of secretory vesicle) oxidizes I- to I0.
3. IONINATION
   TSH also stimulates iodination of thyroglobulin in the follcular lumen
4. CONJUGATION
   TSH stimulates the conjugation of iodinated tyrosines to form T3 and T4 linked to thyroglobulin
5. ENDOCYTOSIS
   TSH stimulates the endocytosis of iodinated thyroglobulin into the follicular cells from thyroid colloid

6.PROTEOLYSIS
TSH stimulates the proteolysis of the iodinated thyroglobulin, forming T4 and 3 in the lumen of the lysoendosome

7. SECRETION
   TSH stimulates the secretion of T4 and T3 into the circulation
8. HYPERPLASIA
   TSH exerts a growth-factor effect, stimulating hyperplasia within the thyroid gland

Question 6

T/S Ratio?

Answer 6

Follicular-cell iodine : Plasma iodine

Thyroid/Serum

Question 7

Stages of synthesis and secretion of t3 and t4?

Answer 7

1. TRAPPING
2. Iodine leaves the cell
3. IONINATION
4. CONJUGATION
5. ENDOCYTOSIS
6. PROTEOLYSIS
7. SECRETION
8. HYPERPLASIA

Question 8

Peripheral metabolism of T4?

Answer 8

Sulphation and glycoslyation by the liver so are more aqueous soluble, so are found in urine

Action by 5’/3’- monodeiodinase enzyme from T4 and T3

Question 9

MoA of thyroid hormones?

Role of TBG?

Answer 9

T3

• Most bound to TBG (thyroxin- binding globulin)
• 5’/3’ monodeiodinase activity removes the 5’ iodine converting T4 to T3.

T4
-Mostly bound to TBG

T4 and T3 enter the cell either by diffusion or by carrier-mediated transport

TBG along with other thyroid hormone binding proteins found in the plasma (e.g. transthyretin and albumin) buffer free T3 and T4 levels in the blood

On entering the nucleus..
T3 binds binds with thyroid hormone receptor (THR)  and Retinoid X receptor (RXR) complex
--> Gene transcription to form
-Na-K pump
-Gluconeogenic enzymes
-Resp enzymes
-Myosin heavy chain
-Beta-adrenergic receptors
-Many others

Question 10

BMR actions of the thyroid hormones

Answer 10

Increase in basal metabolic rate (BMR)

• -> increase O2 consumption
• -> Increase in heat production

Question 11

Effect of hyper or hypo thryoidism on BMR?

Answer 11

Hyperthyroidism= Increase BMR - increases by up to 100%

Hypothyroidis: Decrease BMR - decreases to 50-60%

Question 12

Effect of thyroid hormones on mobilisation on..
Carbohydrates?
Fats?
Proteins?

Answer 12

Carb: Increase in

• Glucose from GIT
• Glucose utilisation
• Liver glycogenolysis and gluconeogenesis

Question 13

Resultant thyroid disorder in goitrogens?

Answer 13

Excess iodide, thiocyanate or perchlorate cause excess TSH secretion and hypertrophy of thyroid and hypothyroidism

Goitrogens are substances that suppress the thyroid gland by interfering with thyroid hormone production. As a compensatory mechanism, the thyroid will enlarge to counteract the reduced hormone production.

Question 14

Resultant thyroid disorder in pit tumours?

Answer 14

• Excess TSH - hypertrophy of thyroid and hyperthyroidism

- Lack of TSH - atrophy of thyroid and hypothyroidism

Question 15

Resultant thyroid disorder in Grave’s disease?

Answer 15

Long-Acting Thyroid Stimulator (LATS- autoimmune stimulation of thyroid) - hypertrophy of thyroid and hyperthyroidism

Presentation: Exophthalmos

Question 16

Resultant thyroid disorder in Hashimoto’s disease?

Answer 16

Autoimmune destruction of thyroid- atrophy of thyroid and hypothyroidism

Question 17

hypothyroidism CNS symptoms?

Answer 17

Poor mental ability

Initiative

Question 18

Fetal hypothyroidism leads to…

Answer 18

Neuronal hypoplasia
Delayed myelination in specific neurones
Mental retardation

Question 19

Thyroid hormone replacement therapy, success?

Answer 19

On thyroxine treatment starting in thyroid deficient children…

• Mental age doesn’t improve
• Height and bone age improves

Question 20

Effect of thyroid hormones on mobilisation on..

Proteins?

Answer 20

Increase in protein turnover with net increase in anabolism

Increase in certain enzymes, membrane proteins and hormone receptors

Question 21

Effect of thyroid hormones on mobilisation on..

Fats?

Answer 21

Increase in lipolysis in apipose tissue so increase in plasma FFA
Increase in tissue oxidation of FFA

Question 22

What is TBG??

Answer 22

TBG (thyroxin- binding globulin)

Buffers free T3 and T4 levels in the blood

Question 23

What converts T4 and T3?

Answer 23

5’/3’ monodeiodinase activity removes the 5’ iodine converting T4 to T3.