Thyroid Hormones

Question 1

What are the physiological effects of thyroid hormones?

Answer 1

1) Growth & development
- essential for brain development (absent T3 -> cretinism)
- promote protein synthesis (skeletal/muscle growth), anabolic at normal concentrations, but catabolic at the levels of hypderthyroidism
2) Metabolic effects
- increase BMR, increase oxygen consumption
- starvation lowers both T3 hormone and thyroid receptor
3) Thermogenesis
- increasing resting heat production
- inability to adjust to environmental temperature is a characteristic sx of hyper or hypo
4) Cardiovascular effects
- increase catecholamine sensitivity

Question 2

Difference between T3 & T4 (structure + activity)

Answer 2

T3: more potent
T4: produced more

Question 3

Iodine

Answer 3

• used for synthesis of thyroid hormones
• best natural food source is seafood
• deficiency was endemic in inland populations
  Goiter - an enlargement thyroid gland due to persistent rise in TSH
  Cretinism - severely stunted physical and mental growth
• routinely added to table salt

Question 4

Where does thyroid transport occur in the body?

Answer 4

in plasma
- Thyroxine-binding globulin (TBG) - primary transport protein
- Transthyretin (TTR)
- Albumin
Transport proteins have greater affinity to T4
- only 0.04% of T4 is free
- T4 has a longer HL than T3, serves as a storage pool (2-3 months)
- T3 has a more rapid onset

Question 5

Thyroid Metabolism

Answer 5

• Deiodination
• Conjugation to form glucuronide or sulfate with the phenolic group
• Excreted via the bile
  
  • some are hydrolyzed by bacteria, marginal enterohepatic circulation

Question 6

Hypothyroidism sx

Answer 6

• decrease in metabolic rate (fatigue, mental dullness, lethargy, inattention)
• defective thermoregulation
• may occur with thyroid enlargement (nontoxic goiter)
• dwarfism and mental retardation (cretinism) in infants and children
• myxoedema coma - end state of untreated hypothyroidism; water intoxication, shock, death

Question 7

4 Causes of Hypothyroidism

Answer 7

• Hashimoto’s Thyroiditis: most common; autoimmune disease that destroys the thyroid gland
• destruction or removal of the gland (radiation, x-ray, thyroidectomy)
• iodine deficiency
• congenital (cretinism)

Question 8

Hyperthyroidism sx (2)

Answer 8

• excessive metabolism - poor thermoregulation and weight loss
• increased heart rate and cardiac output

Question 9

3 Causes of Hyperthyroidism

Answer 9

• Grave’s Disease: most common, autoimmune; thyroid stimulating IgG, enlargement of the entire thyroid gland (diffuse toxic goiter)
• toxic uninodular goiter and toxic multinodular goiter: adenoma producing excess T3, occur mostly in older women
• subacute thyroiditis: viral infection of the thyroid gland, transient release of stored thyroid hormones

Question 10

What drugs are used for thyroid replacement therapy?

Answer 10

hypothyroidism
1) Natural thyroid hormone preparations
non-FDA approved
- desiccated thyroid & thyroglobulin (bovine or porcine)
- variable T4/T3 blood levels due to inconsistencies in sources
2) Levothyroxine (T4)
- converted to T3 intracellularly
- slow onset, long HL (7 days), 6-8 weeks to reach steady state levels
3) Liothyronine (T3)
- rapid onset, short duration of action (24 hr) requiring multiple daily doses
- greater risk of cardiotoxicity
- difficult to monitor using conventional laboratory tests
4) Liotrix (discontinued)
- 4:1 mixture of T4 & T3
- more expensive, but not shown to be more effective than T4 administration alone

Question 11

Hyperthyroidism treatment - Thioamides

Answer 11

• antithyroid agents
• methimazole, propylthiouracil
• used to treat thyrotoxicosis
• inhibit thyroid peroxidases
  
  • block iodine organification + coupling of the iodotyrosines
• slow onset (3-4 weeks)
  
  • require depletion of stored T4

Question 12

Hyperthyroidism treatment - Iodine (I 131)

Answer 12

HL = 8 days
- administered orally in solution as Na131I
Problems:
- hypothyroidism occurs in 80% of pts
- potential increases in certain cancers
- radiation thyroiditis: prevent with pretreatment of antithyroid drugs
Advantage: no surgery and lower cost
Contraindication? not for pregnant women or nursing mothers

Question 13

Hyperthyroidism treatment - Iodide

Answer 13

• large dose of I- inhibits its own uptake, iodine organification, release of thyroid hormones, and decreases vascularity of the thyroid gland
• beneficial effect is transient and thus not used for long-term management
• Lugol’s Solution: aqueous element of I and KI
  Uses: preparation for thyroidectomy, severe thyrotoxicosis, protection from radioactive iodine fallout
  SE: hypothyroidism, sensitivity to iodine in some pts (angioedema)