1. Thyroid hormones
and
antithyroid drugs

3. normal amount of thyroid hormones are essential for normal growth and development by maintaining the level of energy metabolism in the tissue.
Either too little or too much thyroid hormones will bring disorders to the body.

4. Part 1 Thyroid hormones Two major thyroid hormones are:
triiodothyronine（T3, the most active form）
thyroxin（T4）
The characteristic of their chemical structure is that they all contain iodine as an essential part of the molecule.

5. Structure

6. inadequate secretion of thyroid hormone (hypothyroidism) can bring many disorders to the body (eg. bradycardia, poor resistance to cold, both mental and physical slowing.)

7. [Synthesis, storage and release of thyroid hormones]

8. Synthesis
Iodine is the raw material of the thyroid biosynthesis. Once taken up by the thyroid gland, iodine undergoes a series of enzymatic reactions before it converts into active thyroid hormones.

9. Synthesis; four steps
1. iodine trapping :uptake of iodine by the thyroid gland
2. oxidation of iodine: (to its active form)
thyroid peroxidase (key enzyme of the synthesis)
3. iodide organification :the iodination of tyrosyl groups of thyroglobulin
productions: MIT and DIT
4. formation of T4 and T3 from MIT and DIT :
thyroid peroxidase

10. storage
store in the colloid droplets of thyroglobulin

11. release The hormones are released by proteolysis of thyroglobulin .
Enzyme: thyroglobulin hydrolase
The ratio of T4 to T3 within thyroglobulin is about 5:1

12. Differences between T3 and T4
the effect of T3 is much faster, stronger and shorter than that of T4.

13. conversion
T4 can converse to T3 through deniodonite in peripheral tissues as well as in the thyroid.
(catalyzed by deiodinase)

14. Regulation: TRH Hypothalamus pituitary TSH T3,T4 thyroid
Controled by HPT(hypothalamic-pituitary-thyroid) axis

15. Regulation

16. TRH (thyrotropin releasing hormone)
TSH (thyroid stimulating hormone or thyrotropin)

17. [Pharmacokinetics]

18. Pharmacological actions
Effects on growth and development
Calorigenic effects :
Hypersensitivity to catecholamine :

19. Pharmacological actions
1.Effects on growth and development :
responsible for normal growth and maturation of human being , especially for nervous and skeletal tissues.
so the absence of thyroid hormones before birth leads to both mental and physical retardation（cretinism）

20. Pharmacological actions
2.Calorigenic effects:
T3 /T4 can increase oxygen consumption, promote metabolism and BMR（basal metabolic rate） ,↓utility.
So hyperthyroidism will result in excess heat production and body wasting.

21. Pharmacological actions
3. hypersensitivity to catecholamine
Cardiovascular effects:
Tachycardia, hypertension
nervous Effects: anxiety, nervous.

22. mechanism TR
CBP
NUCLEAR R

24. Clinical uses
the major indications for the therapeutic use of thyroid hormones are for hormone replacement therapy in patients with hypothyroidism .

25. Clinical uses 1.Cretinism :congenital hypothyroidism
often happens in newborn babies, mainly caused by iodine deficiency before birth .
Success in the treatment of cretinism depends on the age at which therapy is started.
The earlier, the better.

26. Cretinism Symptoms: 1.Physical slow: dwarf, with short extremities ,
2.mentally retarded: inactive, uncomplaining and listless.
incidence :about 1 per 400 births
Prevention and therapy:
Prevention: Iodine replacement is the best method prior to pregnancy.
Therapy: thyroid hormones replacement(T4 is more often used than T3)

27. Clinical uses 2.Myxedema: adult hypothyroidism
Happens after individual development
Slow in mentality
With special edema
Mortality :60%

28. Clinical uses 3.Simple goiter:
A kind of prevalent disease caused by insufficient dietary iodine
TSH can promote hyperplasy and hypertrophy of thyroid gland.
4. Differential diagnosis of simple goiter and hyperthyroidism

29. Simple goiter

30. adverse reactions
hyperthyroidism

31. Part 2
Antithyroid drugs

33. Grave’s syndrome

34. Treatment of hyperthyroidism
The goal of therapy is to decrease the additional hormone and attend to normal levels.
Can be accomplished by
removing part of the gland
Inhibiting synthesis
Blocking releasing

35. four categories of anti-thyroid drugs
Ⅰ Thioureas : (硫脲类)
interfere directly with the synthesis of thyroid hormones
Ⅱ High concentrations of iodine :
decrease the release of thyroid hormones
Ⅲ Radioactive iodine :
damage the gland with ionizing radiation
Ⅳ β- receptor antagonists:
control the manifestations

37. Ⅰ Thioureas(硫脲类) Thiouracils: methythiouracil , propylthiouracil
Imidazoles:
methimazole , carbimazole.

38. Ⅰ Thioureas Pharmacological action : Mechanism
Decrease the level of thyroid hormones
Mechanism
1.inhibit the thyroid peroxidase :
(key enzyme of synthesis)
interfere the oxidation of iodine and the coupling of MIT and DIT to form T3/T4

39. 2. inhibit conversion from T4 to T3
3.immunosupressive effect: TSI

40. Pharmacokinetics:
Absorption
Distribution
Excretion
Pass through placenta, milk

41. Therapeutic uses 1.As definitive treatment to control hyperthyroidism
2.Preoperative preparations for subtotal thyroidectomy: to control the disorder in preparation for surgical treatment.
(thioureas plus large dose of iodine)
3. Thyroid crisis Propylthiouracil is the first choice.

42. Adverse reactions 1.allergic response 2.GI reaction
3.granulocytopenia (0.3%-0.6%)
4.Longterm use:
goiter and hypothyroidism

43. Drug interactions ↑
Li，sulfasulfonamide，PAS，paraminan（对氨苯甲酸），phenylbutazone，barbital，phentolamine，sulfonyl urea，vitB12 ↓
iodine

44. Ⅱ Iodine and iodide Oldest agent
have completely different effects due to different doses

45. Pharmacological effects
in small dose:
↑ synthesis of thyroid hormones
in large dose : antithyroid
1) ↓the release of thyroid hormones into the circulation: strong
Mechanism: Inhibit thyroglobulin hydrolase
2)↓synthesis of thyroid hormones: weak
Mechanism: Inhibit thyroid peroxidase

46. Therapeutic uses 1.Simple goiter : in small dose
2.In preparation for thyroidectomy :
used after the hyperthyroidism has been controlled by thioureas, given for 7 to 10 days immediately preceding the operation. (The changes after a fairly long term of administration include: the vascularity of the thyroid gland is reduced, the gland becomes much firmer and smaller.)
3.Thryotoxic crisis

47. Adverse reactions 1. Chronic iodism 2.Acute allergic action :
angioneurotic edema and larynx edema
3. Thyroid dysfunction

48. Ⅲ Radioactive iodine 131I : most often used isotope of iodine
γ rays（1%）:
β particles（99%): destructive

49. Effects on the thyroid gland
131I is rapidly and efficiently trapped by the thyroid gland and slowly emitsβparticles and γrays.
The destructive βparticles can destroy the thyroid cells with little damage to surrounding tissues (the penetration range is only mm).
Theγrays can pass through the tissue and be quantified by external detection

50. Clinical uses
1.hyperthyroidism: administrated orally and the effective dose differs for individual patients.
2.diagnosis of thyroid functions

51. pregnancy and milk mothers
Adverse reactions:
hypothyroidism
contraindications
pregnancy and milk mothers

52. IV β-adrenergic receptor antagonists
adjuvant therapy
many of the symptoms of hyperthyroidism are associated with sympathetic stimulation, so β-R blockers are effective in antagonizing the catecholaminegic symptoms such as tachycardia, palpitations ,anxiety and tension.

53. Action: (1)block 1-R of heart (2)block -R of CNS
(3) block -R of presynaptic membrane of peripheral nerve.
(4) Inhibit T4 converted into T3

54. Uses:
1.Control the symptoms of
hyperthyroidism before
confirmed diagnosis
2.Thyroid crisis
3.Preoperation of hyperthyroidism
4.Hyperthyroidism

55. Section 3
TSH and TRH

56. Thank you!