Thyroid Gland Physiology

Question 1

Which enzyme converts T4 –> T3 or reverse T3 in the periphery?

Answer 1

• T4 –> T3 through outer ring deiodination via deiodinases type 1 and 2
• T4 –> reverse T3 through inner ring deiodination via deiodinase type 3

Question 2

Which clinical states are associated with reduction in conversion of T4 –> T3?

Answer 2

• Fasting
• Medical and surgical stress
• Catabolic diseases

Question 3

Which enzyme liberates the I- from recycled MIT and DIT to be reused within the thyroid follicular cell?

Answer 3

• Intrathyroidal deiodinase

- Deficiency of this enzyme mimics dietary I- deficiency

Question 4

Pendred syndrome

Answer 4

• Mutation in the Pendrin gene (SLC26A4 aka PDS) causing defects in the transport of I-/Cl- across the apical membrane of the thyroid follicular cells
• Also impacts the cochlea
• Pt presents w/ hypothyroidism, goiter and sensorineural hearing loss

Question 5

Describe the Wolff-Chaikoff effect

Answer 5

-High circulating lvls of I- transiently inhibit the organification and synthesis of thyroid hormones in an attempt to prevent the thyroid from synthesizing large quantities of TH

Question 6

Perchlorate and thiocyanate

Answer 6

• Competitive blockers for the Na+/I- synporter on the basolateral membrane of the thyroid follicular cell
• Used to decrease thyroid hormone synthesis in hyperthyroidism pts

Question 7

Propylthiouracil (PTU)

Answer 7

• Inhibits thyroid peroxidase (PTO) activity

- Used to decrease thyroid hormone synthesis in hyperthyroidism pts

Question 8

Expected values of total T4 and T3 resin uptake compared to normal in pts w/: Hyperthyroidism

Answer 8

• total T4: increased

- T3 resin uptake: increased (more T4 competing for same # of binding spots on TBG)

Question 9

Expected values of total T4 and T3 resin uptake compared to normal in pts w/: Hypothyroidism

Answer 9

• total T4: decreased

- T3 resin uptake: decreased (less T4 competing for same # of binding spots on TBG)

Question 10

Expected values of total T4 and T3 resin uptake compared to normal in pts w/: high TBG

Answer 10

• total T4: increased

- T3 resin uptake: decreased

Question 11

Expected values of total T4 and T3 resin uptake compared to normal in pts w/: low TBG

Answer 11

• total T4: decreased

- T3 resin uptake: increased

Question 12

Expected values of TBG and T3 resin uptake compared to normal in pts w/: hepatic failure

Answer 12

• TBG: decreased –> transient increase in free T3, T4 which inhibits synthesis of T3, T4 resulting in
• T3 resin uptake: increased

Question 13

Expected values of TBG and T3 resin uptake compared to normal in pts w/: pregnancy

Answer 13

• TBG: increased due to excess estrogen production
• increased bound T3 and T4 w/ decrease in free T3 and T4 –> transient decrease in free T3, T4 lvls causes an increase in synthesis and secretion of T3, T4 –> increase in total T3 and T4 lvls but amount of free T3, T4 are normal (clinically euthyroid)
• T3 resin uptake: decreased

Question 14

Actions of thyroid hormones on lipid metabolism

Answer 14

1. Stimulates fat mobilization –> increase [FA] in plasma
2. Enhances oxidation of FA
3. Plasma [cholesterol] and [triglycerides] inversely correlated w/ thyroid hormones –> increased blood [cholesterol] in hypothyroidism
4. Required for conversion of carotene to vitamin A (hypothyroid pts can suffer from blindness and yellowing of skin)

Question 15

Actions of thyroid hormones on carbohydrate metabolism

Answer 15

1. Increased gluconeogenesis and glycogenolysis to generate free glucose
2. Enhanced insulin-dependent entry of glucose into cells

Question 16

Cardiovascular effects of thyroid hormones

Answer 16

Main goal is to increase cardiac rate/output to increase blood volume:

1. Direct:
   a) increases cardiac muscle myosin heavy chain alpha/beta ratio
   b) stimulates synthesis of cardiac Beta1-adrenergic receptors
   b) increases ventricular contractility and function
   c) decrease peripheral vascular resistance
2. Indirect: increase heat production and CO2 in tissues –> decrease peripheral vascular resistance –> decrease diastolic BP –> reflex increase adrenergic stimulation

Question 17

Actions of thyroid hormones on growth

Answer 17

-Act synergistically w/ growth hormone and someatomedins to promote bone formation

Question 18

Actions of thyroid hormones on CNS

Answer 18

• important for CNS maturation and deficiency during perinatal period leads to:
  a. abnormal development of synapses
  b. decreased dendritic branching and myelination

Question 19

Major clinical signs and lab findings in Graves’ disease

Answer 19

• Exophthalmos and periorbital edema
• Elevated serum free and total T4 or T3 lvls and decreased TSH lvls w/ signs of goiter and ophthalmopathy
• Presence of circulating thyroid-stimulating immunoglobulins distinguish Graves’ disease from adenoma of pituitary thyrotrophs

Question 20

Hashimoto’s thyroiditis

Answer 20

• primary hypothyroidism caused by production of thyroglobulin or thyroid peroxidase antibodies which attack the thyroid gland
• Labs will show decreased T3 and T4 with high TSH lvls and clinical signs of goiter due to TSH

Question 21

Sheehan syndrome

Answer 21

• postpartum hypopituitarism secondary to necrosis of pituitary gland –> caused by acute hemorrhage during child birth that resulted in a rapid drop of BP which shunted blood away from brain
• Most pts present w/ agalactorrhea
• Can also see amenorrhea and hypothyroidism (secondary disorder)