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 1st
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
 I131
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 1st
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 I131
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