It's very important for care of thairoid patient

2. Thyroid gland
One of largest endocrine glands in the body.
Site:
Located in the neck just below the larynx, on either side of
& anterior to the trachea.

3. Thyroid gland
Formed of 2 lobes (Rt & Lt), that are connected by
band of tissue called “isthmus”.
Not visible under normal conditions, but can be felt
during swallowing.

4. Thyroid gland structure
Follicles (Acini):
Are the functional unit.
Each follicle is spherical in structure &
filled with proteinaceous material
called colloid which contains large
glycoprotein called thyroglobulin
which stores thyroid hormones
within its molecules.

5. Thyroid gland secretions
- Secreted by Parafollicular cells.
- Important hormone for Ca2+ metabolism & homeostasis.
● 2 important thyroid hormones:
● Thyroxine (T4) or tetraiodothyronine
● Triiodothyronine (T3)
Secreted by Follicular cells.
Calcitonin

6. Chemical nature of thyroid hormones
I
HO
COOH
CH2-CH
O
T3 has : - 2 benzene rings
- 3 iodine atoms (contains 59% iodine)
- COOH & NH2 groups like an amino acid.
NH2
I
I
T4 has : - 2 benzene rings
- 4 iodine atoms (contains 65% iodine)
- COOH & NH2 groups like an amino acid.
O
I I
I
CH2-CH
HO
I
COOH
NH2

8. 1-Uptake of Iodide:
Found in food in the form of “iodide (I-) is actively
transported (trap) into the follicle by a symporter or iodide
pump : Na+/ I- symporter (NIS)
2- Oxidation & Iodination/Organification:
• Conversion of the iodide ions to an oxidized form of iodine
by the enzyme peroxidase in presence of H2O2.
• Iodine immediately reacts with tyrosine residue on a
“thyroglobulin” to form MIT & DIT , called as
organification or iodination
Both processes are catalyzed by thyroidal peroxidase enzyme

9. 1 Iodine + 1 tyrosine  Mono-iodo-tyrosine (MIT)
2 Iodine + 1 tyrosine  Di-iodo-tyrosine (DIT)

10. 3- Condensation (coupling):
MIT & DIT or 2 DIT molecules coupled together, reaction
catalyzed by same peroxidase
MIT + DIT = T3
DIT + DIT = T4
T3 can also be formed by de-iodination of T4 by deiodinase
4- Proteolysis of Colloid &Thyroid hormones
secretion:
These hormones are released by exocytosis and proteolysis of
thyroglobulin.

12. HORMONE TRANSPORT .
 T4 and T3 are reversibly bound to thyroxine binding
globulin (TBG).
 0.04% of total T4 and 0.4% of T3 exist in free form
 Starvation , pregnancy , steroid hormones affects their
binding , but their free concentration is maintained in
euthyroid gland

13. PERIPHERAL METABOLISM
 The primary pathway of peripheral T4 metabolism is
DEIODINATION.
 Converstion of T4 in to T3.

14. MECHANISM OF ACTION
 Free form of T3 and T4 enter cell by diffusion
/active transport .
 T4 is converted to T3 & enters nucleus & binds to
T3 receptors, this leads to increased formation of
mRNA and subsequent protein synthesis.

15. THYROID REGULATION
 Thyroid-pituitary relationship
 Thyrotropin releasing hormone (TRH) is secreted by
hypothalamic cells in pituitary portal venous system.
 It acts on pituitary, causes synthesis and release of thyroid
stimulating hormone (TSH).
 This in turn acts on thyroid cells to increase release and
synthesis of T3 and T4.
 Autoregulation of thyroid gland

16. Hypothalamic –pituitary – thyroid axis
Thyroid regulation

17. Functions of thyroid hormones
1. Increases metabolic rate. Stimulates increased
consumption of glucose, fatty acids and other
molecules.
2. Increases metabolic heat, by  mitochondrial no. &
activity   ATP
3. Stimulates rate of cellular respiration by:
 Production of uncoupling proteins.
 Stimulates O2 consumption of most of cells in
the body.

18. Functions of thyroid hormones
4. Necessary for normal growth & maturation.
5. Promotes maturation of nervous system.
6. Promotes development of skeletal & reproductive
tissues
7. Stimulates protein synthesis.
8. Help regulating lipid & CHO metabolism.

19. Thyroid preparations
LEVOTHYROXINE:(T4)
 This is the preparation of choice for thyroid replacement &
suppression therapy, because it is stable, content uniform,
lack allergenic protein, easy lab measurement of serum
levels, low cost and has a long (7 days) half life, to be
administered once daily.
 T4 converted to T3 , so its administration produces both
hormones.

20. LIOTHYRONINE(T3):
 More potent (3-4 times) & rapid acting than
levothyroxine but has a short half life (24 hours) &
costly as compared to levo, is not recommended for
routine replacement therapy, as it requires multiple
dosing in a day. Also difficult lab monitoring and
more risk of cardiotoxicity.

22. CLASSIFICATION
1- Thioamides
Methimazole
Carbimazole
Propylthiouracil
2- Anion inhibitors
Perchlorate (ClO4)
Pertechnetate(TcO4)
Thiocynate (SCN)

23. 3- Iodides
Lugol solution
Potassium iodide
4- Radio active iodine
131 I
5- Iodinated contrast media
Ipodate
Iopanoic acid
Diatrizoate

24. 6- Adrenoceptor- blocking Agents
Metoprolol
Propanolol
Atenolol

25. THIOAMIDES
 Methimazole
 Carbimazole
 Propylthiouracil
 Methimazole is 10 times more active than
propylthiouracil.

26. Mechanism of Action
They act by:
 Inhibits organification and coupling reaction.
 Propylthiouracil also inhibits the peripheral conversion
of T4 to T3.

28. .
Pharmacokinetics:
 Well absorbed orally, distributed all over the body
 Methimazole  long duration once-daily
 Carbimazole is a pro-drug converted in the liver to its active
metabolite methimazole.
 Serum half life: 90mins(PTU) ; 6 hours (methimazole)
 Excretion: kidney – 24 hours (PTU) ; 48 hours
(Methimazole)
 Can cross placental barrier (lesser with PTU)
 Methimazole 10x more potent than PTU
 PTU more protein-bound

29. Adverse Effects
 GIT distress, nausea are earlier effects.
 Maculopapular rash & fever.
 Rare : Urticarial rash, vasculitis, arthralgia
,cholestatic jaundice, lymphadenopathy, &
hypoprothrombenemia.
 Altered sense of taste or smell & cholestatic
jaundice with methimazole
 Severe hepatitis with PTU
 Most dangerous complication is agranulocytosis ,
infrequent but may be fatal.

30. IODIDES
 Lugol's solution (5 % iodine + 10 % potassium iodide) 3-5
drops orally tid.
 Potassium iodide 1-3 drops orally tid.
Mechanism of action:
 Inhibit organification
 block the effect of TSH on the thyroid gland, so decrease the
size & vascularity.

32. Toxicity:
 Overdoses of iodine may cause iodism (metallic
taste, excessive salivation, with painful salivary
gland, diarrhea, productive cough, running eyes &
nose, sore throat and rashes; mimic chicken-pox).
 Iodine therapy maximizes iodine stores in the
thyroid. This effect delays the response to
thionamides.

33. RADIOACTIVE IODINE
The beta radiations of 1131 destroy thyroid parenchyma,
so decreasing hormonal release.
Advantages:
Easy administration (orally).
Effectiveness.
Absence of pain
It is not expensive.
Suitable for old ages and cardiac patients with
moderate to severe hyperthyroidism and unfit for
surgery.

34. Adverse effects:
 As with iodine therapy, overdoses may cause iodism.
 Local pain & congestion at the site of the gland.
 Permanent Hypothyroidism.
 Malignant changes in the thyroid after many years
Contraindications:
Pregnancy, children , nursing mother & under the age of 20
years

35.  receptor blockers
•Control manifestations of sympathetic over activity
•It decreases the peripheral conversion of T4 to T3

36. ANION INHIBITORS
 Perchlorate (ClO4
-) ; pertechnetate(TcO4
-) &
thiocynate (SCN-) block uptake of iodide by the
gland by competitive inhibition
 Can be overcome by large doses of iodides
 They are rarely used clinically now days as they
cause aplastic anemia.

38. HYPOTHYRODISM
It is a syndrome resulting from deficiency of thyroid
hormones and manifested by reversible slowing down of all
body function.
Infants and children suffer severely , results in dwarfism
and irreversible mental retardation
Diagnosed by low free thyroxine and elevated serum TSH
For treatment : replacement therapy is appropriate
Levothyroxine is most satisfactory: Infants and children
require more T4 / kg body weight than adults.

39. 39
 Thyroxine is given once daily due to long half life.
 In older patients and in patients with underlying cardiac
diseases treatment is started with reduced dose
 levothyroxine (T4) is given in a dose of 12.5 – 25 µg/day
for two weeks and then increasing it after every two weeks.

40. ADVERSE EFFECTS OF OVER DOSE OF
THYROXINE
 CHILDEREN : Restlessness, insomnia, accelerated
bone maturation.
 ADULTS : Nervousness, heat intolerance ,
palpitation, weight loss
 Atrial fibrillation and osteoporosis in chronic over
treatment with T4.

41. MYXEDEMA COMA
 It is an end state of untreated hypothyroidism.
 Serious medical emergency, mortality rate high (60%)
despite early diagnosis and treatment.
 Profound hypothermia, respiratory depression,
unconscious, bradycardia, delayed reflexes, dry skin.
 The treatment of choice is loading dose of levothyroxine
I/V 300-400µg initially followed by 50-100mcg daily.
 I/V T3 can be used but it may prove cardiotoxic
 I/V hydrocortisone it may be used in case of adrenal and
pituitary insufficiency.

42. HYPOTHYROIDSM AND
PREGNANCY
 These woman suffer form anovulatory cycles and
infertility
 In pregnant hypothyroid patient 20-30 % increase
in thyroxine is required because of
 elevated maternal TBG and
 early development of fetal brain which depends
on maternal thyroxine

43. HYPERTHYROIDISM
This is the syndrome that results when tissue is
exposed to high levels of thyroid hormone.
GRAVES' DISEASE
Most common form of hyperthyroidism.
It is autoimmune disorder
There is genetic defect
antibodies against thyroid antigens.
T3 and T4 are elevated and TSH is suppressed.

44. Management of Grave’s disease
 Drug therapy
 Surgical thyroidectomy
 Destruction of the gland with radioactive iodine

45. Drug therapy:
 When patient is young with small gland and mild
disease
 Methimazole / propylthiouracil until disease undergoes
spontaneous remission.
 This may take 1-2 years with 60-70 % relapse.

46. THYROIDECTOMY
 A near-total thyriodectomy is the treatment of choice in
very large gland or multinodular goiter

47. RADIOACTIVE IODINE 131I
 Preferred in most patients over 21 years of age.
 In patients with underlying heart disease, severe disease &
in elderly patient use methimazole until patient become
euthyroid , then stop the medicine for 5-7 days before
giving 131I
 Major complication of this therapy is hypothyroidism which
occurs in 80% of patients.

48. Adjunct Therapy
 During acute phase β-blockers without intrinsic
sympathomimetic activity are extremely helpful eg
: Propranolol
 Diltiazem 90-120 mg TDS, when β-blockers
contraindicated
 Barbiturates
 Cholestyramine

49. THYROID STORM
 It is sudden acute exacerbation of all of the symptoms of
thyrotoxicosis, presenting as a life threatening syndrome.
 There is hyper metabolism, and excessive adrenergic
activity, death may occur due to heart failure and shock.
 Vigorous management is mandatory.

50.  Propranolol 1-2mg slow I/V or 40-80 mg orally every 6
hours
 Potassium iodide 10 drops orally daily or
 Iodinated contrast media (Na ipodate 1 g orally daily)
 Propylthiouracil 250 mg orally every six hours or 400 mg
every six hours rectally.
 Hydrocortisone 50 mg I/V every 6 hours to prevent shock.
 If above methods fail plasmapheresis or peritoneal dialysis.

51. Thyrotoxicosis during pregnancy
 Definitive therapy with 131I or subtotal thyroidectomy prior
to pregnancy to avoid acute exacerbation during pregnancy
or after delivery
 During pregnancy radioiodine is contraindicated.
 Propylthiouracil is better choice during pregnancy. Dose
must be kept minimum i.e., <300 mg daily.