Endocrine 4 (Thyroid)

Question 1

What hormones are secreted by the Thyroid Gland

Answer 1

Thyroxine T4
Tr-Iodothyronine
Calcitonin

Question 2

Synthesis of Thyroid Hormone

Answer 2

1. Plasma iodide is taken up by follicle cells
2. Iodination of Thyroglobulin
   - Thyroperoxidase + H2O2 oxidizes iodine and incorporates iodine into Tyrosine residues of thyroglobulin
3. Secretion of Thyroid Hormone

Question 3

Regulation of Thyroid Hormone

Answer 3

Thyrotropin-Releasing Hormone (TRH) and Protirelin (Synthetic Tripeptide) causes anterior pituitary to release Thyroid Stimulating Hormone (TSH)

TRH + Protirelin = TSH Release

Question 4

Action of TSH
- Receptor

Answer 4

TSH acts on GPCRS in Thyroid Follicle Cells
- Increase in CAMP
- Activation of PI3K

Question 5

Action of TSH
- Trophic Action

Answer 5

Increases Na+/I- Symporter
- More iodine into cell

Synthesis of Thyroglobulin
Secretion of Thyroglobulin into Follicle

Generation of H2O2
- Greater stimulus of thyroperoxidase to incorporate iodide into tyrosine of thyroglobulin

Endocytosis of Thyroglobulin

Secretion of T3 and T4

Increased blood flow through the gland

Question 6

Vascularity of the Thyroid Gland

Answer 6

Heavily vascularized
- Uptake in the thyroid gland is very rapid

Question 7

Causes of Hypothyroidism

Answer 7

Hashimoto’s Disease
- Antibodies against thyroglobulin leading to decreased thyroid hormone secretion

Question 8

Symptoms of Hypothyroidism

Answer 8

Low metabolic rate
Slow speech
Bradycardia
Sensitivity to cold
Myxedema (Severe Cases)
- Waxlike consistency and thickening of skin

Question 9

Thyroid Replacements
- MOA

Answer 9

Treats Hypothyroidism by replacing action of T3/T4

When no T3 (Natural Conformation):
- Histone Deacetylation (Loose)
- Does not interact with transcription factors
- Transcriptional Repression

When T3 Present
- Histone Acetylation (Tight)
- Interacts with transcription factors
- Transcriptional Activation

Question 10

Thyroid Replacements
- T3 vs T4

Answer 10

T4 is deiodinated to T3 (By Dio1)

T4 is a pro-hormone
- Slower acting, large reserves

T3 is turned over more rapidly, smaller pool

Question 11

Thyroid Replacements
- Effects

Answer 11

T3:

Metabolism:
- Increased Body Temp
- Decreased Weight

Cardiovascular:
- Increased Heart Rate
- Increased Blood Pressure

GI
- Increased Motility

Musculoskeletal
- Skeletal Development
- Peak Bone Mass

Reproductive
- Enhance Ovulation
- Enhance Spermatogenesis

Does not have a direct effect, rather affects other hormones that have secondary impact

Question 12

Thyroid Replacements
- Adverse Effects

Answer 12

• Tachycardia
• Atrial Fibrillation

Question 13

Causes of Hyperthyroidism

Answer 13

Grave’s Disease AKA Diffuse Toxic Goitre
- Antibodies against thyrotropin receptor lead to overstimulation and an increase of thyroid hormone secretion

Hyperthyroidism = Thyrotoxicosis

Question 14

Symptoms of Hyperthyroidism

Answer 14

High Basal Metabolism
- Increased Appetite
- Weight Decrease

Increased Skin Temperature
Heat Intolerance

Sweating
Nervousness and Tremor
Tachycardia

Question 15

Radioiodine
- MOA

Answer 15

Treats Hyperthyroidism
1st Line Treatment using (131)I

Taken up like normal iodine by the thyroid

Beta Particles of Isotope have a:
- Short range (Weakly penetrating), and only stay within the thyroid
- Cytotoxic action, destroys the thyroid gland

Takes a month before it takes action

Question 16

Radioiodine
- Considerations

Answer 16

Avoid use in children
Avoid use in pregnancy

After destruction of gland individual becomes hypothyroid and needs administration of Levothyroxine (T4)

Question 17

Antithyroids (Thioamides)
- MOA

Answer 17

Thiocarbamide (S-C-N) has antithyroid activiy
- Prevents synthesis of thyroid hormone

Inhibits Thyroperoxidase
Block Iodine Oxidation

Block Coupling of Iodinated Tyrosine

Inhibit Peripheral Deiodination of T4 to T3

Question 18

Antithyroids (Thioamides)
- Adverse Effects

Answer 18

Skin Rash (Common)

Neutropenia (More serious but rare)
Agranulocytosis (More serious but rare)

Do not use if Pregnant

Question 19

Antithyroids (Excess Iodine)

Answer 19

Lugol Iodine
- Solution of potassium iodide + iodine in water
- Used in severe thyrotoxicosis or preparation for surgery

Question 20

Antithyroids (Excess Iodine)
- MOA

Answer 20

Lugol Iodine will cause an excess amount of iodide resulting in a negative feedback that inhibits thyroid hormone secretion

• Reduces vascularity of thyroid gland
• Reduce H2O2
  –> Inhibits iodination of thyroglobulin