Thyroid Hormones

Question 1

triiodothyronine

Answer 1

T3

Question 2

thyroxine

Answer 2

T4

Question 3

Thyroid hormone preparation of T4

Answer 3

Levothyroxine (given orally, long half life)

Question 4

T3 aka

Answer 4

triiodothyronine

Question 5

T4 aka

Answer 5

thyroxine

Question 6

Thyroid hormone preparation of T3

Answer 6

Liothyronine (more potent, faster acting but short half life, injectable)

Question 7

When do you give T3?

Answer 7

T3 given only when an immediate response is needed (E.g. in myxodema coma)

Question 8

MOA of thyroid hormones

Answer 8

➢ Thyroid hormones are attached to plasma carrier proteins.
• Hormones dissociate from carrier proteins enter the cell by active transport

➢ Within the cell T4 converted to T3 – enters nucleus- bind to thyroid hormone receptor - localized in the nucleus –> Stimulates transcription of particular genes

Question 9

Levothyroxine

Answer 9

T4 hormone prep

Question 10

Effects of Thyroid hormones on growth & development

Answer 10

• Essential for normal physical & mental growth, hence cretinism - mental retardation

Question 11

caloric effects of thyroid hormones

Answer 11

• ↑ BMR and

* ↑ manitain body temperature

Question 12

Liothyronine

Answer 12

T3 hormone prep

Question 13

cardiovascular effects of thyroid hormones

Answer 13

• ↑ HR and

* ↑ peripheral resistance

Question 14

metabolic effects of thyroid hormones

Answer 14

• ↑ blood sugar,
• ↑ synthesis of fatty acids and
• decrease plasma CH and TG levels

Question 15

Use of thyroid hormones

Answer 15

➢ Hypothyroidism caused by:

• Hashimoto’s disease
• Myxedema
• Following surgical ablation of thyroid gland

Question 16

hypothyroidism signs and symptoms

Answer 16

• anemia;
• hyponatremia,
• galactorrhea,
• goiter;
• hard, pitting edema of the lower extremities
• delayed return of deep tendon reflexes
• Any combination of a few or many signs and symptoms may occur at any given time.
• Some signs and symptoms, such as galactorrhea, anemia, and skin changes are seen in individuals in later stages of hypothyroidism.

Question 17

Thyroid Inhibitors:

Answer 17

• Perchlorate,
• thiocyanate,
• goitrin

Question 18

Thyroid Hormone Synthesis

Answer 18

1. Uptake of Iodide (iodide trapping)
2. Iodide organification
   • (oxidation and iodination)
3. Coupling of MIT and DIT
4. Secretion of thyroid hormones
5. Conversion of T4 to T3

Question 19

Ionic Inhibitors

Answer 19

Affects uptake of Iodine

• Perchlorate (ClO4- )
• thiocyanate (SCN- )

➢ No Therapeutic use: only Diagnostic

Question 20

Monovalent anions

Answer 20

Affects uptake of Iodine

• Resemble Iodide
• Inhibit transport of iodide into thyroid

➢ No Therapeutic use: only Diagnostic

Question 21

Thyroid peroxidase

Answer 21

Oxidizes iodide to iodine

Question 22

Thioamides

Answer 22

Antithyroid drug!

➢ Iodine rapidly iodinates tyrosine residues in thyroglobulin forming MIT (mono-iodotyrosine) and DIT (di-iodotyrosine)

• Inhibited by: Thioamides

Question 23

Coupling of MIT and DIT

Answer 23

➢ Coupling reaction involves oxidation by:
• Thyroid peroxidase

1. MIT + DIT –> T3
2. DIT + DIT –> T4

➢ Stored in thyroglobulin in colloid matrix
• Inhibited by thioamides -

examples:
• Methimazole
• Propylthiouracil

Question 24

Thioamides MOA

Answer 24

➢ Inhibit thyroid peroxidase :
• Block iodine oxidation
• Coupling of MIT and DIT

Question 25

Propylthiouracil MOA

Answer 25

Inhibit peripheral conversion of T4 to T3 • Block synthesis T3 and T4 not release, therefore slow onset of action

Question 26

Thioamides A/E

Answer 26

``` ➢ Relatively low incidence (3 – 12%) • Maculopapular pruritic rash • Hypothyroidism • Gastrointestinal intolerance • Agranulocytosis ( ```

Question 27

Secretion of T4 and T3 Inhibited by:

Answer 27

Iodine and Iodides

Question 28

Secretion of T4 and T3

Answer 28

➢ Proteolysis - release of T4 and T3 stored within thyroglobulin (TG) • MIT and DIT deiodinated; iodine reutilized ➢ Inhibited by Iodine and Iodides

Question 29

Iodides

Answer 29

➢ Inhibit TH release - thyroid constipation ➢ Decreased size & vascularity of gland ➢ Improvement of thyrotoxic symptoms occurs rapidly – used in thyroid storm

Question 30

Conversion of T4 to T3 Inhibited by

Answer 30

* Propranolol * Propylthiouracil * Glucocorticoids (prednisolone)

Question 31

Conversion of T4 to T3:

Answer 31

➢ 80% of T4 converted to T3 in peripheral tissues • De-iodination of T4 (thyroxine) to active T3 (triiodothyronine)

Question 32

Lugol’s Iodine and Na/K Iodide: • use • toxicity

Answer 32

Use: • Preoperatively- thyroidectomy • Thyroid storm Toxicity: • Iodism- rash, rhinorrhoea, ulcers, conjuctivitis

Question 33

Radioactive Iodine * what * half life

Answer 33

I-131 ➢ Rapidly absorbed (orally) ➢ Concentrated in thyroid ➢ Emits b radiation --> destruction of thyroid gland • half life (5 days)

Question 34

Use of radioactive iodine • advantages • disadvantages • contraindicated

Answer 34

Use: Hyperthyroidism Advantage: • Inexpensive, simple, outpatient basis • No surgical risk • Permanent cure Disadvantage: • response slow • Hypothyroidism Contraindicated: • pregnancy, • young patients

Question 35

Treatment of Hyperthyroidism

Answer 35

➢ Antithyroid drug therapy • Propylthiouracil, methimazole ➢ Thyroidectomy ➢ 131Iodine

Question 36

Thyroid Storm • triggers • treatment • what is it

Answer 36

aka thyrotoxic crisis • high mortality Triggers: • Acute illness, surgery, radioiodine in an untreated thyroid. Treatment: • Large doses of Propylthiouracil: inhibit the peripheral conversion • Propranolol - control cardiac manifestations • Potassium iodide – inhibit release of thyroid hormones • Glucocorticoids- protect against shock, block conversion of T4 to T3

Question 37

What is Thyroid Storm

Answer 37

Thyroid storm is a crisis or life-threatening condition characterized by an exaggeration of the usual physiologic response seen in hyperthyroidism. Whereas hyperthyroidism can cause symptoms such as sweating, feeling hot, palpitations and weight loss - symptoms of thyroid storm are more severe, resulting in complications such as: * fever * dehydration * rapid heart rate * nausea/vomiting * diarrhea * irregular heart beat * weakness * heart failure * confusion/disorientation * death

Question 38

Propranolol

Answer 38

beta blocker ➢ Many symptoms of thyrotoxicosis - sympathetic stimulation- palpitation, nervousness, tremors • b-blockers - Block physiological effects of sympathetic nervous system stimulation