GREEK :- THYREOS – SHIELD ; EIDOS – FORM 1.LOCATION:- Anterior to trachea in between the cricoid cartilage and the suprasternal notch. 2.SHAPE:- It has 2 lobes connected with an isthmus, each lobe in turn has two poles. 3.Weighs around 10-20 gm, highly vascular and soft in consistency. 4. 4 Parathyroid glands which secrete PTH are located posterior to each pole of thyroid The RLN traverse the lateral border of thyroid gland and must be identified during thyroid surgery to avoid injury and vocal cord paralysis. Develops from the floor of primitive pharynx during the 3rd week of gestation. Fetal cells in which developmental transcription factors TTF-1,TTF-2 & PAX-8 are expressed selectively form the thyroid gland ,secondly they result in induction of thyroid specific genes Tg,TPO,NIS,TSH-R. Mutations-THYROID AGENESIS & DYSHORMONOGENESIS(CONG. HYPOTHYROIDISM). The developing gland migrates along the thyroglossal duct to reach its final location in the neck. LINGUAL THYROID AND THYROGLOSSAL DUCT CYST. Thyroid hormone synthesis begins at about 11 weeks of gestation. Until 11 week of gestation and even later, it is the maternal thyroid hormones which cross the placenta to reach the fetus and aid its development. Therefore a child born to a hypothyroid mother would suffer from features of congenital hypothyroidism. Secondly if the mother has TSH-R blocking antibodies or has received anti thyroid therapy during pregnancy, might lead to transient congenital hypothyroidism.

1. HYPOTHYROIDISM
A.Vikas
1

2. CONTENT
1.ANATOMY
2.PHYSIOLOGY
3.PATHOLOGY
4.MANAGEMENT
2

3. ANATOMY3

4. GREEK :- THYREOS – SHIELD ; EIDOS – FORM
1.LOCATION:- Anterior to trachea in between the cricoid cartilage
and the suprasternal notch.
2.SHAPE:- It has 2 lobes connected with an isthmus, each lobe in
turn has two poles.
3.Weighs around 10-20 gm, highly vascular and soft in consistency.
4. 4 Parathyroid glands which secrete PTH are located posterior to
each pole of thyroid.
4

5. 5

6. The RLN traverse
the lateral border of
thyroid gland and
must be identified
during thyroid
surgery to avoid
injury and vocal
cord paralysis.
CLINICAL IMPORTANCE6

7. EMBRYOLOGY
Develops from the floor of primitive pharynx during the 3rd week
of gestation.
Fetal cells in which developmental transcription factors
TTF-1,TTF-2 & PAX-8 are expressed selectively form the thyroid
gland ,secondly they result in induction of thyroid specific genes
Tg,TPO,NIS,TSH-R.
Mutations-THYROID AGENESIS &
DYSHORMONOGENESIS(CONG. HYPOTHYROIDISM).
7

8. The developing gland migrates along the thyroglossal
duct to reach its final location in the neck.
LINGUAL THYROID AND THYROGLOSSAL DUCT
CYST.
Thyroid hormone synthesis begins at about 11 weeks of
gestation.
8

9. So till the fetal thyroid gland
begins to function who has to
provide it with thyroid
hormones??
9

10. MATERNAL THYROID HOMONES10

11. Until 11 week of gestation and even later, it is the maternal
thyroid hormones which cross the placenta to reach the fetus
and aid its development.
Therefore a child born to a hypothyroid mother would suffer
from features of congenital hypothyroidism.
Secondly if the mother has TSH-R blocking antibodies or has
received anti thyroid therapy during pregnancy, might lead to
transient congenital hypothyroidism.
11

12. PHYSIOLOGY
Structural and functional units – THYROID FOLICLES.
The follicles are made up of polarized cuboidal epithelial cells
which synthesise and secrete thyroid hormones.
Apart from these the thyroid also harbors the neural crest
derivatives – C cells / Para follicular cells responsible for
CALCITONIN production(minimal role in Ca homeostasis in
humans but r imp coz of their involvement in medullary thyroid
carcinoma).
12

13. Synthesis of Thyroid hormones
13

14. 14

15. Short term stimulation by TSH results in
phosphorylation of various :-
1.Transcription factors
2.Enzymes
3.Transport proteins
Which would result in increased function of the gland.
Long term stimulation(Grave’s) results in production
of special transcription factors which stimulate the
genome and not only results in increased function but
also results in hypertrophy and hyperplasia resulting
in goiter formation.
15

16. 16

17. 17

18. 18

19. 19

20. Clinical importance
PENDRED SYNDROME :-
1.Defective organification of iodine.
2.Goiter.
3.Sensorineural deafness.
LOW T3 SYNDROME :- In catabolic stressful conditions
like starvation, trauma & surgery, body tries to prevent
further catabolism due to T3 by inhibiting 5’ deiodenase
{Pt’s serum :- ↓ T3, Normal T4 & TSH levels}
20

21. After synthesis upon stimulation by TSH the hormones are
secreted into circulation.
↓
90-93% T4 , 7-10% T3.
↓
T4 compared to T3 has high affinity towards TBG , TBPA & TBA,
and about 99% of secreted hormones bind to these proteins.
↓
<1% of T3 & T4 is in free form.
21

22. T4 – STORAGE
FORM.
T3 – ACTIVE
FORM.
22

23. HPT AXIS
It is the
circulating T4
levels which
regulate the TSH
secretion and not
the T3 levels.
23

24. Mechanism of action of T3
24

25. Transcription of many genes.25

26. FUNCTIONS OF THYROID
HORMONE.
26

27. ↑BMR
Physical growth
&
Mental
maturation
Keeps tissues
sensitive to
adrenergic drive.
27

28. ↑ BMR
PROTEINS
FUNCTIONAL STRUCTURAL REGULATORY
↓
Mitochondrial
enzymes
↓
Physical and
mental growth
↓
Transport proteins
Eg :- Na/K ATPase
LDL receptors
T3 & T4 act on all
cells in the body to
↑BMR except on :-
CNS,Retina,L.N,
Spleen & gonads.
28

29. Physical and mental growth
Thyroid hormones directly as well indirectly by
increasing the synthesis & production of GH & PTH
enhance the bone development.
T3 & T4 are essential for development of :-
1.Dendrites
2.Synapses
3.Myelination
29

30. Effect on specific bodily mechanisms by
enhancing expression of adrenergic receptors.
On GIT :- Increases acid secretion, digestion and
absorption of glucose and also enhances GI motility.
On liver :- 1.Enhances β receptor mediated glycogenolysis
& gluconeogenesis.
2.Increases expression of LDL receptors on the surface of
hepatocytes thereby increasing its uptake & resulting in
low blood cholesterol levels.
30

31. On Adipocytes :- Enhances β3 mediated lipolysis thereby
increasing FFA concentration in the blood, which is
utilised by actively metabolising cells for β oxidation and
by liver for gluconeogenesis.
On Pancreas :- Enhances insulin secretion.
On heart :- Increases expression of β receptors, myosin
proteins & Ca ATPases, thereby increasing HR &
myocardial contractility(↑SBP , ↓DBP ).
On lungs :- ↑(RR & TV) = ↑Minute ventilation.
31

32. On CNS :- T3 & T4 increase the expression of
adrenergic receptors & alter the NT activity, thus
maintain the normal CNS function.
On Gonads :- Maintain libido and fertility in both males
and females.
32

33. ORGAN/
STRUCTURE
HYPERTHYROIDISM HYPOTHYROIDISM
HAIR THIN THICK & UNMANAGABLE
CNS ALERT,ANXIOUS,
INSOMNIA, PARANOID.
MR,Lack of conc.,
DEPRESSED,
SOMNOLANCE.
EYES EXOPHTHALMOS,LID
LAG.
PERIORBITAL
PUFFINESS.
SKIN WARM,SWEATY THICK,SCALY,COLD –
GEN. MYXEDEMA WITH
YELLOWISH TINGE.
VOICE ANXIOUS,SHRILL HOARSENESS
R.S TACHYPNEA BRADYPNEA
33

34. CVS TACHYCARDIA ,TACHY
ARRYTHMIA,HIGH
OUTPUT CARDIAC
FAILURE
BRADYCARDIA,
BRADYARRYTHMIA,
LOW OUTPUT
CARDIAC FAILURE
S.CHOLESTEROL HYPO
CHOLESTEROLEMIA
HYPER
CHOLESTEROLEMIA
WHICH RESULTS IN
ACCELERATED
PHASES OF
ATHEROSCLEROSIS
GIT INCREASED APPETIE,
INCREASED BOWEL
MOVEMENTS &
WEIGHT LOSS
DECREASED
APPETITE,
CONSTIPATION,
WEIGHT GAIN
34

35. MALE GENITAL
SYSTEM
LOSS OF LIBIDO &
INFERTILITY
LOSS OF LIBIDO,
IMPOTENCE &
INFERTILITY.
FEMALE
GENITAL
SYSTEM
OLIGOMENRRHOEA
INFERTILITY
MENORRHAGIA,
POLYMENORRHOEA
& INFERTILITY
35

36. Presence of goiter does not reveal the
function status of thyroid gland i.e it can be
present in :-
1.Hyperthyroid state
2.Euthyroid state
3.Hypothyroid state
36

37. 37

38. 38

39. CAUSES OF HYPOTHYROIDISM
PRIMARY :- When the pathology lies in the gland itself.
1.Congenital :- Agenesis (mutations in TTF-1&2,PAX-8).
Dyshormonogenesis(Tg,TPO,NIS,TSH-R).
Ectopic thyroid gland.
2.Iodine deficiency
3.Autoimmune :- Hashimoto’s thyroiditis
4.Iatrogenic :- 131 I treatment, subtotal/total thyroidectomy.
39

40. 5. DRUGS :- Iodine excess(wolf chaikoff effect),
anti thyroid drugs , Li.
6. Infiltrative disorders :- Amyloidosis, Sarcoidosis &
Scleroderma.
Iodine deficiency remains the most common cause of
hypothyroidism worldwide.
In areas of iodine sufficiency Hashimoto’s thyroiditis &
iatrogenic causes are most common.
40

41. SECONDARY / CENTRAL :-
When the pathology lies in the ant. pitutary or hypothalamus.
1.HYPOPTIUTARISM :- Tumors, Surgery/Irradiation, infiltrative
disorders, trauma, Sheehan’s syndrome.
Sheehan’s syndrome :- aka Simmond’s syndrome/ postpartum
hypopituitarism.
Mech :- Blood loss / hypovolemic shock during or after child birth
↓
Decreased blood supply to pituitary leading to its ischemic necrosis.
41

42. 2. HYPOTHALAMIC DISEASE :- Tumors,
Trauma, Infiltrative disorders.
Isolated TSH deficiency / inactivity.
42

43. Hashimoto’s thyroiditis
Definiton :- Autoimmune destruction of thyroid gland & gradual
& progressive thyroid failure.
Classification :-
1.Hashimoto’s / goitrous thyroiditis – Initial stage where there is
a phase of compensation when normal thyroid hormone levels
are maintained by a rise in TSH(Sub clinical hypothyroidism).
2.Atrophic thyroiditis :- Late stages with minimal residual
thyroid tissue(↓Unbound T4, ↑↑TSH, symptoms become more
apparent – Clinical / Overt Hypothyroidism).
43

44. Pathogenesis
Caused by a breakdown in self tolerance to thyroid
autoantigens.
Ass. with polymorphisms in immune regulation associated
genes :- HLA DR-3,4,5;CTLA-4;
Mech of thyroid destruction :-
1.CD8+ cytotoxic T cell mediated cell death.
2.Cytokine(INF-γ) mediated cell death.
3.Antibody dependent cell mediated cytotoxicity.
44

45. 45

46. Laboratory Evaluation
1.Primary Hypothyroidism :- ↓Unbound T4;↑TSH; ↑TRH.
Along with these in Hashimoto’s :- Tg & TPO antibodies can
be elicited(FNAC can be done to demonstrate Hurthle cells in
conjugation with heterogenous group of lymphocytes
characteristic of hashimoto’s).
2.Secondary / Central Hypothyroidism :-
Hypopitutarism :- ↓Unbound T4; ↓ TSH; ↑TRH.
Hypothalamic cause :-↓Unbound T4; ↓ TSH; ↓ TRH.
46

47. Differential diagnosis :-
An assymetric goiter in hashimoto’s may be confused with a
MNG/ thyroid carcinoma, in which thyroid antibodies may
also be present.
In such cases USG can be done:-
1.In MNG – multiple nodules can be appreciated
2.In thyroid carcinoma – solitary lesion.
3.Hashimoto’s – Heterogenous thyroid enlargement.
47

48. 48

49. TREATMENT
The treatment goal in hypothyroidism is to achieve normal TSH
levels which are elevated.
1.Pt’s with no residual thyroid function :- Daily replacement
dose of levothyroxine(1.6 μg/kg = 100-150μg) ideally taken at
least 30 min before breakfast.
2.Pt’s who develop hypothyroidism after treatment of Grave’s :-
Due to underlying autonomous function they require lower
replacement doses (75-125μg).
49

50. 3.Adult patients <60 yr without evidence of heart disease :-
Started on 50-100 μg levothyroxine daily.
2 months after treatment depending on TSH levels
adjustment of levothyroxine dosage is made in 12.5 or 25 μg
increment if TSH is high & decrement if TSH is suppressed.
NOTE :- Elevated TSH levels inspite of appropriate
medication indicates Pt’s poor adherence to treatment.
50

51. 4.Subclinical hypothyroidism :- Biochemical evidence
of thyroid hormone deficiency in Pt’s who have few or
no apparent C/F.
Treatment is considered if Pt is a female who wishes to
conceive/ is pregnant /TSH >10mIU/L(over 3 month
period) or <10mIU/L with TPO+/suggestive symptoms.
Low dose levothyroxine(25-50 μg/day)with goal of
normalising TSH.
51

52. 5. Maternal Hypothyroidism :- It requires early
detection & effective treatment as it can adversely affect
fetal neural development & cause premature delivery.
The levothyroxine dose may need to be increased by up
to 50% during pregnancy with a goal of TSH< 2.5
mIU/L during the 1 trimester & <3 mIU/L during 2 & 3
trimester.
52

53. It is a severe form of hypothyroidism leading to reduced level of
consciousness, may be ass. with seizures and hypothermia(23˚C).
It is a medical emergency.
Treatment includes :-
1.Loading dose – Single IV bolus of 500μg levothyroxine
2.Maintenance dose :- 50-100 μg/day
Supportive therapy to correct ass. Metabolic disturbances.
External warming if temp <30˚ or else can result in cardiovascular
collapse,parenteral hydrocortisone(50mg/6 hrly) as there is impaired
adrenal reserve.
MYXEDEMA COMA53

54. REFERENCES
 1.HARRISON’S PRINCIPLE OF INTERNAL MEDICINE.
 2.ROBBINS PATHOLOGY.
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