THYROID HORMONE

THYROID HORMONE

1. DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
ESIC MEDICAL COLLEGE, GULBARGA.
DEPT. OF PHYSIOLOGY
THYROID
HORMONE.

2. OBJECTIVES.
Functional Anatomy.
Gross anatomy
Histological structure
Thyroid hormones
Biosynthesis & Storage
Secretion, transport & Metabolism.
Regulation of thyroid hormone secretion.
Applied aspects
Hyperthyroidism
Hypothyroidism.

3. FUNCTIONAL ANATOMY.
GROSS ANATOMY
Largest endocrine
gland
15-25 gm
Consists of 2 lobes
joined by narrow
Isthmus.
High blood supply –
400-600ml/100g/min.
Tuesday, February 20, 2018

4. HISTOLOGICAL STRUCTURE
Each lobe divide3d
into lobules by fibrous
septa.
Each lobules made up
of several follicles.
Each follicle lined by
Follicular cells.
Tuesday, February 20, 2018

5. HISTOLOGICAL STRUCTURE
Follicular cells.
Cuboidal & contains colloid.
Secrete Thyroid Hormones.
Parafollicular cells (C cells).
Between follicular cells
Secrete Calcitonin.
Colloid.
Homogenous material in each
follicle
Contains Thyroglobulin.
Tuesday, February 20, 2018

6. THYROID HORMONES
2 Principal Hormones
Tri-iodothyronine T3
Thyroxine T4
T3 – 10% , Responsible for
most of tissue actions.
T4 – 90%
Calcitonin – hormone
secreted by Parafollicular
cells, concerned with Calcium
Homeostasis.
Tuesday, February 20, 2018

7. IODINE METABOLISM
Dietary Intake – rich sources –
sea fish, bread milk, vegetables
Avg intake – 500 μg
Daily Requirement – 100-200
μg.
Fate – 80% of iodides absorbed
from GIT removed by thyroid
gland.
Plasma iodide – 0.15 – 0.3 μg.
Thyroid Iodide – contains 5-8 mg.
(95% of total iodide content)
Tuesday, February 20, 2018

8. THYROID HORMONES
BIOSYNTHESIS & STORAGE
Iodine trapping
Synthesis &
secretion of
thyroglobulin
Oxidation of iodides.
Organification of
thyroglobulins.
Coupling reaction.
Storage.
Tuesday, February 20, 2018

9. IODINE TRAPPING
Uptake of iodide by thyroid
gland.
By Iodine pump or Na/I
–
symporter.
Thyroid stimulating
hormone – controls iodide
uptake.
Anti-thyroid agents –
Thiocynate & Perchlorate
inhibit Iodide transport.
Tuesday, February 20, 2018

10. SYNTHESIS & SECRETION OF
THYROGLOBULIN
Thyroglobulin – large Glycoprotein synthesized in
rough endoplasmic reticulum of thyroid epithelial
cells & then released into lumen.
1 molecule of Thyroglobulin contains – 140
thyrosine residue which is a substrate for iodine for
thyroid hormone synthesis.
Tuesday, February 20, 2018

11. Tuesday, February 20, 2018

12. OXIDATION OF IODIDES.
Once inside gland iodide is taken into lumen by
transporter – Pendrin.
Then iodide is oxidised to Iodine by enzyme
Peroxidase.
Tuesday, February 20, 2018

13. ORGANIFICATION OF
THYROGLOBULINS.
Iodination of tyrosine
residue in thyroglobulin
molecule.
Tyrosine is 1
st
iodinated
at position 3 to form
Mono-iodotyrosine
(MIT) & then at position
5 to form Di-
iodotyrosine (DIT)
Tuesday, February 20, 2018

14. COUPLING REACTION.
One molecule of MIT &
DIT coupled to form
Tri-iodothyronine
(T3)
2 molecules of DIT
coupled to form
Thyroxine (T4)
Tuesday, February 20, 2018

15. STORAGE.
Once Thyroglobulin is
iodinated is stored in
lumen.
Stored thyroid
hormones can meet
body requirements for
1-3 months.
Tuesday, February 20, 2018

16. SECRETION
Endocytosis – colloid
containing iodinated
Thyroglobulin is secreted by
Endocytosis.
Colloid enters the cytoplasm
as colloid droplets.
Proteolysis – colloid droplets
fuses lysosome vesicles
containing proteolytic
enzymes & releases T3,T4,
MIT & DIT.
Tuesday, February 20, 2018

17. TRANSPORT
Bound form – most of
T3 & T4 are bound to
specific proteins.
Thyroxine binding
Globulins – bind 70%
of T3 & T4.
Free form – 0.5% of
T3 & 0.05% of T4.
Tuesday, February 20, 2018

18. METABOLISM
Deiodination – about 40%
T4 deiodinated into T3 by
enzyme 5’-deiodinase.
Decarboxylation – very
few decarboxylated to form
tetraiodothyroacetic acid &
tri-iodothyroacetic acid.
Conjugation – 15% T3 & T4
are conjugated in liver to
form glucoronides &
sulphates.
Tuesday, February 20, 2018

19. REGULATION OF THYROID
HORMONE SECRETION.
Through Negative
Feedback
Auto Regulation of
thyroid gland.
Tuesday, February 20, 2018

20. THROUGH NEGATIVE
FEEDBACK
Tuesday, February 20, 2018

21. AUTOREGULATION OF
THYROID GLAND.
Thyroid gland
secretion regulated by
food iodine.
Iodine content in diet
& iodine trapping are
inversely
proportional.
Tuesday, February 20, 2018

22. MECHANISM OF ACTION OF
THYROID HORMONE
Tuesday, February 20, 2018

23. ACTIONS OF THYROID
HORMONE
Effect on growth & tissue
development.
Effect on metabolic rate in general.
Effects on metabolism.
Carbohydrate
Fats
Proteins
Vitamins
Respiratory effects.
Cardiovascular effects.
Effects on nervous system
Development
Functioning of nervous tissue
Effects on GIT.
Effects on reproductive system
Effects on other endocrine
glands.
Effects on kidney.
Tuesday, February 20, 2018

24. EFFECT ON GROWTH & TISSUE
DEVELOPMENT.
Role in normal body
growth & skeletal
maturation.
Bone development
Teeth development.
Role in tissue
differentiation &
maturation.
Role in development of
nervous tissue.
Tuesday, February 20, 2018

25. EFFECT ON METABOLIC RATE
IN GENERAL.
Stimulate metabolic
activities
Increases basal rate of
oxygen consumption
and heat production.
Tuesday, February 20, 2018

26. EFFECTS ON METABOLISM.
Carbohydrate – increase glucose absorption & metabolism.
Fats – Mobilization of fats from adipose tissue 7 decreases
plasma cholesterol levels.
Proteins – Physiologically anabolic effect & in high conc
catabolic effect.
Vitamins – increases quantity of enzymes so causes vitamin
deficiency.
Tuesday, February 20, 2018

27. RESPIRATORY EFFECTS.
Increase in resting
respiratory rate, minute
ventilation &
ventilatory response to
hypercapnia & hypoxia.
Increase in oxygen
carrying capacity of
blood.
Tuesday, February 20, 2018

28. CARDIOVASCULAR EFFECTS.
Tachycardia.
Increase force of cardiac
contraction.
Increase cardiac output.
Blood pressure – systolic
increases & diastolic
decreases.
Vasodilatation & increased
blood flow to tissue.
Tuesday, February 20, 2018

29. EFFECTS ON NERVOUS SYSTEM
Development
Functioning of
nervous tissue.
Effect on functioning
of nervous tissue.
Tuesday, February 20, 2018

30. EFFECTS ON GIT.
Increase in appetite &
food intake.
Increase in rate of
secretion of digestive
juices.
Increase in motility of
GIT.
Tuesday, February 20, 2018

31. EFFECTS ON REPRODUCTIVE
SYSTEM
In Males – lack of
hormones causes loss
of libido & excess
causes Impotence.
In Females –
menorrhagia &
Polymenorrhagia.
Irregular periods &
Amenorrhoea.
Tuesday, February 20, 2018

32. EFFECTS ON OTHER
ENDOCRINE GLANDS.
Pituitary,
adrenocortical
secretion & oestrogen :
androgen ratio
increased.
Parathyroid & 1,25-
(OH)
2
– Vit D decreased.
Tuesday, February 20, 2018

33. EFFECTS ON KIDNEY.
Renal plasma flow
GFR
Tubular transport
maximum.
Tuesday, February 20, 2018

34. APPLIED ASPECTS
Hyperthyroidism
Hypothyroidism.
Tuesday, February 20, 2018

35. HYPERTHYROIDISM
Increased secretion of
Thyroid hormones.
Causes are
Grave’s disease
Toxic Nodular Goitre.
Tuesday, February 20, 2018

36. GRAVE’S DISEASE
THYROTOXICOSIS.
Aetiology
Autoimmune disease
Thyroid stimulating
Antibodies against TSH
receptors.
Bind with receptors &
mimics TSH effect
Thyroid Hyperplasia.
Tuesday, February 20, 2018

37. SIGNS & SYMPTOMS
General features –
BMR
Wt loss, heat intolerance
Goitre – swelling of thyroid gland.
Cardiovascular features –
Sinus tachycardia
Arrhythmia
Neuromuscular features
Nervousness, Irritability,
restlessness, Psychosis, tremors,
Muscle weakness.
Tuesday, February 20, 2018

38. SIGNS & SYMPTOMS
Gastrointestinal – Diarrhea,
steatorrhoea & vomiting
Dermatological –
Perspiration, loss of hair,
redness of palm.
Reproductive
Males – Impotence
Females – Amenorrhoea,
Oligomenorrhoea, abortion &
Infertility.
Ophthalmological –
Exopthalmos.
Tuesday, February 20, 2018

39. INVESTIGATIONS
Both T3, T4 – raised.
TSH – low
I
131
uptake –
TRs antibodies –
Serum Cholesterol – less
ECG – Tachycardia, arrythmia.
USG – Diffuse Goitre.
Tuesday, February 20, 2018

40. HYPOTHYROIDISM.
Syndrome by low levels
of thyroid hormones.
Aetiology –
Primary – Thyroid
disorder.
Secondary –
Hypothalamus or Ant
Pituitary disorder.
Tuesday, February 20, 2018

41. CLINICAL FEATURES
Infantile
Hypothyroidism
( Cretinism) –
Adult
Hypothyroidism
Tuesday, February 20, 2018

42. INFANTILE HYPOTHYROIDISM
( CRETINISM) –
Hypothyroidism in 1
st
yr
of life.
Mental retardation,
marked retardation of
growth, delayed
milestone development,
pot belly, protruding
tongue, flat nose, dry
skin & sparse hairs.
Tuesday, February 20, 2018

43. ADULT HYPOTHYROIDISM
(MYXODEMA)
Due to infiltration of skin
by Myxodematous
tissue.
Clinical features –
General – Tiredness,
weight gain, cold
intolerance, decreased
sweating.
CVS – Bradycardia,
Anaemia.
Tuesday, February 20, 2018

44. ADULT HYPOTHYROIDISM
(MYXODEMA)
Clinical features –
Neurological Features – lethargy,
slow movements, speech,
sleepiness, delayed reflexes.
Skin – toad skin, sparse hair,
myxoedema
Reproduction – Menorrhagia,
infertility, Galactorrhoea &
Impotence.
GIT – constipation & Adynamic
Ileus.
Tuesday, February 20, 2018

45. GOITRE
Abnormal increase in thyroid
gland.
Goitrogenic – causes Thyroid
enlargement.
Thiocynates, perchlorates, thiourea,
thiouracil
Plants – Cabbage, cauliflower.
Iodine deficiency / endemic –
daily intake below 10 μg
Tuesday, February 20, 2018

46. THYROID FUNCTION TESTS
Measurement of
basal metabolic rate.
Normal BMR – ±20%
Hyperthyroidism –
100%
Hypothyroidism - -30
to -40%
Radioactive iodine
uptake (RAIU) - by I
131
Tuesday, February 20, 2018

47. THYROID FUNCTION TESTS
Normal value 20-40%
Hyperthyroidism –
60%
Hypothyroidism –
20%
Measurement of Total
& Free T3, T4 & TSH
USG thyroid gland
Thyroid scan
Tuesday, February 20, 2018

48. THYROID FUNCTION TESTS
Anti thyroid
antibodies.
Fine needle aspiration
Biopsy.
Tuesday, February 20, 2018

49. NORMAL VALUES OF T3, T4,
TSH
Tuesday, February 20, 2018

50. ANTITHYROID DRUGS
Drugs inhibiting
iodine trapping by
Thyroid.
Drugs inhibiting
oxidation of iodide &
coupling.
Drugs inhibiting
release of Thyroxine
(T3,T4)
Tuesday, February 20, 2018

51. THANK
YOU