3. THYROID HORMONES
• Thyroid gland secretes 3 hormones:
1.Thyroxine(t4)
2.Triiodothyronine(t3)
3.Calcitonin
• Out of this calcitonin is produced by parafollicular
C cells and concerned with the Ca2+ balance
• Other two is produced by thyroid follicles
5. SYNTHESIS OF T4 & T3 FOLLOWS 5
STEPS:
1. Iodide uptake
2. Oxidation and iodination
3. Coupling
4. Storage and release
5. Peripheral conversion of t4 to t3
7. Numerical Facts
• Daily req of iodine – 1-2 mcg/kg
• Iodised salt – 100 mcg/gm of salt
• Normal blood iodide – 0.2-0.4 mcg/dl
• Daily production of T4 – 70-90mcg/day
• T3 60-80 mcg/day
• Normal bound T4 – 4.5-11mcg/dl
• T3 – 60-180ng/dl or 0.1-0.2 mcg/dl
• Free T4 – 0.03-0.08%
• Free T3 – 0.2-0.5%
8. TRANSPORT
• Thyroid hormones bind to plasma
proteins-
1.Thyroxine binding globulin (TBG)
2.Thyroxine binding prealbumin
(transthyretin)
3.Albumin
10. T4 T3
• 15 times more protein
bound
• T1/2 6-8 days
• Secretion more than T3
• Mainly a transport form
• Prohormone of T3
• Converted to T3 in
periphery
• Less bound
• 1-2 days
• 5 times more potent than
T4
• Active form, act faster
11. METABOLISM AND EXCRETION
• Metabolic inactivation occurs by
deiodination, glucoronide/sulfate
conjugation.
• Liver is the primary site, also take place in
salivary glands and kidneys
• Conjugates excreted in bile undergo
enterohepatic circulation
• Excreted in urine
12. DRUGS THAT INHIBIT
PERIPHERAL CONVERSION OF
T4 TO T3• Propranolol
• Propylthiouracil
• Amiodarone
• Corticosteroids
• Ipodate
13. THYROID PREPARATIONS
• LEVOTHYROXINE(T4)
• LIOTHYRONINE(T3)
• LIOTRIX 4:1 mixture of t4 and t3
• DESSICATED OR ARMOUR THYROID – derived
from dried and defatted bovine or porcine
thyroid glands
14. ACTIONS
• Growth and development: Essential for normal
growth and development.
• Intermediary metabolism: Marked effect on lipid,
carbohydrate and protein metabolism.
• Calorigenesis: BMR is maintained.
• CVS: Heart rate, contractility and output are
maintained.
• GIT: Propulsive activity.
15. • Nervous system: maturation of nervous system.
Deficiency leads to mental retardation and
cretinism.
• Skeletal muscle: needed for normal muscle
contour. Muscles bcom flabby and weak in
myxoedema.
• Kidney: Rate of urine flow is maintained
• Haemopoiesis: Facilitatory to erythropoiesis.
• Reproduction: Indirect effect on reproduction.
17. USES OF T4 & T3
• The most important uses of thyroid hormone is
in the replacement therapy namely in:
1. Cretinism
2. Adult hypothyroidism
3. Myxoedema coma
4. Nontoxic goiter
5. Thyroid nodule
6. Papillary carcinoma of thyroid
7. Some empirical uses
18. CRETINISM
SPORADIC CRETINISM – defect in thyroid hormone synthesis
ENDEMIC CRETINISM – due to extreme iodine deficiency
TREATED WITH THYROXINE 8-12mcg/kg DAILY
MENTAL RETARDATION ONLY PARTIALLY REVERSIBLE
CRETIN FACIES
19. Adult hypothyroidism
• Commonest endocrine disorder due to
thyroiditis, thyroidectomy
• I131, lithium, iodide, amiodarone cause
hypothyroidism
• Treat with low dose of levo thyroxine daily
and increase every 2-3 wks to 100-
200mcg/day
• Subclinical hypothyroidism – euthyroid status,
raised TSH levels to be treated with T4
20. Myxedema coma
Lio thyronine acts faster but
high risk of arrythmias, 10 mcg
8 hrly
L- thyroxine 200-500mcgiv
followed by 100 mcg iv OD till
oral therapy substituted
Corticosteroids, ventilatory
support, correction of
hyponatremia and
hypoglycemia
21. Non toxic goitre
SPORADIC- DEFECT IN HORMONE
SYNTHESIS
ENDEMIC – IODINE DEFICIENCY
ENDEMIC GOITRE AND CRETINISM
DUE TO IODINE DEFICIENCY IN
PREGNANT MOTHERS IS
PREVENTED BY 150-200MCG ORAL
IODINE DAILY
IODISED SALT- 100MCG IODINE/
GM OF SALT
25. The Chernobyl Nuclear Disaster
25th April 1986:
The accident at reactor 4 occurred
during an experiment to test a
potential safety emergency core
cooling feature.
• 115,000 people evacuated and 220,000
people relocated
• 6,000 cases of thyroid cancer
• 5.5 million people still live in contaminated
areas
• 31 people died in 3 months of radiation
poisoning
• 134 emergency workers suffered from acute
radiation sickness
• 25,000 rescue workers died since then of
diseases caused by radiation
Cancer afflicts many others
Increased birth defects, miscarriages,
and stillbirths
High number of suicide and violent
death among Firemen, policemen, and
other recovery workers
26.
27. PATHOLOGIES
• Grave’s disease – autoimmune disorder,
antibodies to TSH receptor- bind and stimulate
thyroid cells producing TSH like effects, but TSH
levels are low due to feedback inhibition
• Toxic nodular goitre
• Endemic goitre – in iodine deficient
regions, intake of GOITRINS – cabbage,
turnip, mustard, cauliflower, radish
30. MECHANISM OF ACTION
Inhibit iodination of tyrosine
residues in thyroglobulin
Inhibit coupling to form T4 and T3
Inhibit peripheral conversion of T4
to T3 only with propylthiouracil
31. PROPYLTHIOURACIL CARBIMAZOLE
Less potent
Highly plasma protein
bound
Less transfer across
placenta, preferred in
pregnant and nursing
women
T1/2 1-2 hrs
Single dose for 4-8hrs
No active metabolite
2-3 daily doses needed
Inhibit peripheral
5 times more potent
Less bound
Not used in pregnant and
nursing women
T1/26-10 hrs
Single dose for 12-24 hrs
Active metabolite -
methimazole
Single daily dose needed
Does not Inhibit peripheral
conversion of T4 to T3
33. THERAPEUTIC USES
THYROTOXICOSIS
• Grave’s disease. Clinical improvement after 1-2
wks
• Toxic nodular goitre
PREOPERATIVELY
• Render euthyroid before subtotal thyroidectomy
ALONG WITH
RADIO IODINE
• Till radio iodine acts
• To prevent initial hyperthyroidism when radio
iodine given due to release of stored t4
34. ANTI THYROID DRUGS
ADVANTAGES
No surgical risk
No injury to parathyroid
and recurrent laryngeal
nerve
Hypothyroidism-
reversible
Used in children and
young adults
DISADVANTAGES
Life long treatment
High relapse rate
Not used in
uncooperative patient
Drug toxicity
Fetal hpothyroidism and
goitre
35. IODINE AND IODIDES
FASTEST ACTING THYROID INHIBITOR ,WITH
PEAK AT 10-15 DAYS
• LUGOL’S IODINE – 5% IODINE IN 10% POT IODIDE
Inhibits iodide trapping, oxidation, coupling,
endocytosis, proteolysis, hormone release –
THYROID CONSTIPATION/WOLF-CHAIKOFF EFFECT
• ON STOPPING THYROID ESCAPE OCCURS-
THYROTOXICOSIS RETURN WITH GREATER SEVERITY
38. IONIC INHIBITORS
• They inhibit iodide trapping by the thyroid
• Toxic and not used now
• Thiocyanates cause liver, kidney, brain and bone marrow
toxicity
• Perchlorates cause fever, aplastic anemia and agranulocytosis
• Nitrates – weak drugs, cause methhemoglobinemia
39. RADIOACTIVE IODINE I131
Xrays Beta particles
MOA- concentrated by the thyroid colloid, emits radiation from
within the follicles, half life of 8 days
ADMINISTERED AS SODIUM SALT, DISSOLVED IN WATER AND TAKEN ORALLY
For diagnostic
purposes 25-100
microcurie used
For treatment
Penetrate 0.5-2mm of tissue
So no damage to neighbouring tissue
3-6millicurie in grave’s disease and toxic
nodular goitre
40. RADIOACTIVE IODINE
ADVANTAGES
No surgical risk
No injury to parathyroid
and recurrent laryngeal
nerve
Permanent cure
As OP procedure and
inexpensive
DISADVANTAGES
hypothyroidism
Long latent priyan
Not used in
uncooperative patient
Drug toxicity
Fetal hpothyroidism and
goitre
41. • Emergency due to acute hyperthyroidism precipitated
by trauma, surgery, diabetic ketoacidosis, toxemia of
pregnancy
• Not rendered euthyroid before surgery are at risk. GA
or stress of procedure precipitates it
THYROID STORM / THYROTOXIC CRISIS
42. THYROID STORM / THYROTOXIC CRISIS
• SUPPORTIVE MEASURES:
Maintain airway and breathing with ventilatory
support
Maintain circulation with iv fluids and rehydrate
External cooling by wet sponging
Control fever with paracetamol
Correct electrolytic disturbances
Anxiolytic – to suppress anxiety
Antibiotics if necessary
Plasmapheresis – to remove large amounts of
43. • PHARMACOLOGICAL MEASURES:
1. Non selective beta blocker – propranolol
Rapid control of sympathetic symptoms-palpitations, sweating, myopathy
Peripheral conversion of T4 to T3
Inhibit adrenergically evoked tremor by direct action on beta2 receptors
and inhibit increase in blood flow to skeletal muscles, also inhibiting
glycogenolysis and lipolysis that provide fuel to skeletal muscles
DOSE – 1-2 MG SLOW IV FOLLOWED BY 40-80MG ORAL 6TH HOURLY
THYROID STORM / THYROTOXIC CRISIS
44. 2. Propylthiouracil – 200-300mg 6th hrly orally
• Inhibit thyroid hormone synthesis
• Inhibit peripheral conversion of T4 to T3
3. Iopanoic acid – 0.5-1gm oral OD
• Inhibit thyroid hormone release
• Inhibit peripheral conversion of T4 to T3
4. Corticosteroids- hydrocortisone 100mg iv 8th hrly followed by oral
prednisolone
• Treat adrenal insufficiency
• Inhibit peripheral conversion of T4 to T3
5. Diltiazem – 60-120mg 0ral BD in asthmatic pts with thyroid storm and if
tachycardia not controled by propranolol
THYROID STORM / THYROTOXIC CRISIS
45. 23 May 2007 Czech Technical University in Prague 45
