An overview of the physiology of the thyroid and a discussion on management of hypothyroidism.

1. A C ASE PRO FIL E
O F TH YRO ID
D ISEASE
- Dr.Mohammed Siraj
- Dr.Parvez Khan
- Dr.Mohammed Sadiq Azam
- Dr.Praneetha Gayathri
1

2. TH YRO ID GL AN D
H O RM O N O GEN ESIS
2

3. Thyroid Regulation
HYPOTHALAMUS - TRH
ANT. PITUITARY - TSH
TSH -R
THYROID T4 and T3
PLASMA T4 + FT4
PLASMA T3 + FT3
TISSUES FT4 to FT3, rT3 3

4. 4
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5. In the Thyroid Gland
There the following 5 steps in the hormonogenesis
 Trapping of inorganic Iodine from dietary Iodides
 Activation of Iodine to high valance I2
 Incorporation of I2 into Tyrosine of Thyroid Globulin
 Coupling of formed MIT and DIT to form T4 & T3
 Proteolysis of Thyroglobulin to release T4 & T3
5

6. The Thyronines
Mono Iodo Tyrosine – MIT
Di Iodo Tyrosine – DIT
Tri Iodo Thyronine – T3 – half life 6 hours
Tetra Iodo Thyronine – T4 half life 7 days
Reverse T3 - metabolically inactive
T4 is 99.9% protein bound to TBG, TPA, TA
T3 is 99.5% protein bound to TBG, TPA, TA
Bound hormones are inactive – should not be measured
6
Only Free T4 and Free T3 are metabolically active

7. The Thyroxines
Tri Iodo Thyronine – T3
- 10% is from thyroid gland
- 90% derived from conversion of T4 to T3
Tetra Iodo Thyronine – T4
- Is exclusively from thyroid gland
From the thyroid gland
- 80% of hormone secreted is T4
7
- 20% of hormone secreted is T3

8. Throid hormones in peripheral
tissues
• Plasma transport by
thyroxine binding globulin TBG -75 -80%bound
• Transthyretin 10-15%
• Albumin 5-10%
8

9. 9

10. Thyroid Function Tests
 TSH
 Free T4
 Free T3
 Anti-Thyroid Antibodies
 Nuclear Scintigraphy
 FNAC of nodule
10

11. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
NORMAL
LOW
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
11

12. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
NORMAL
EUTHYROID
LOW
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
12

13. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
NORMAL
PRIMARY
LOW
HYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
13

14. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
PRIMARY
HYPERTHYROID
NORMAL
LOW
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
14

15. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
NORMAL
SECONDARY
LOW
HYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
15

16. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
SECONDARY
HYPERTHYROID
NORMAL
LOW
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
16

17. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
NORMAL
SUB-CLINICAL
HYPERTHYROID
LOW
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
17

18. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
NORMAL
SUB-CLINICAL
HYPOTHYROID
LOW
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
18

19. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
NORMAL
LOW
NON THYROID
ILLNESS or NTI
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
19

20. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
NTI or Pt.
on ELTROXIN
NORMAL
LOW
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
20

21. BASIC THYROID EVALUATION
FREE THYROXINE or FT4
HIGH
PRIMARY NTI or Pt. SECONDARY
HYPERTHYROID on ELTROXIN HYPERTHYROID
NORMAL
SUB-CLINICAL SUB-CLINICAL
HYPERTHYROID EUTHYROID HYPOTHYROID
SECONDARY NON THYROID PRIMARY
LOW
HYPOTHYROID ILLNESS - NTI HYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
21

22. THYROID HORMONES
TEST REFERENCE RANGE
TSH Normal Range 0.3 - 4.0 mU/L
Free T4 Normal Range 0.7-2.1 ng/dL
TSH upper limit will soon be revised to 2.5 mU/L
22

23. Thyroid Antibodies
• Anti Microsomal (TM ) Antibodies
• Anti Thyroglobulin (TG) Antibodies
• Anti Thyroxine Per Oxidase (TPO) Ab.
• Anti Thyroxine antibodies
• Thyroid Stimulating (TSA) Antibodies
 High titres TPO Ab in Hashimotos & Reidle’s thyroiditis
 Anti thyroxine Ab in peripheral resistance to Thyroxine
 TSA (TSI) in Graves’ Hyperthyroidism 23

24. hypothyroidism
24

25. Hypothyroidism
• Epidemiology
• Most common endocrine disease
• Females > Males – 8 : 1
• Presentation
• Often unsuspected and grossly under diagnosed
• 90 % of the cases are Primary Hypothyroidism
• Menstrual irregularities, miscarriages, growth retard.
• Vague pains, anaemia, lethargy, gain in weight
25

26. Disease Burden
 5% of the general population are Sub-clinically
Hypothyroid
 15 % of all women > 65 yrs. are hypothyroid
 Detecting sub-clinical hypothyroidism in pregnancy
is highly essential – order for TSH and FT4 routinely
in all pregnant women at the beginning of each
trimester
 All persons aged above 60 years – Order for TSH26

27. • Primary hypothyroidism with Goitre
Aquired
Hashimotos thyroiditis
Iodine deficiency
Drugs blocking synthesis or release of T4
Goitrogens
Cytokines
Thyroid infiltration
Causes of
Congenital
Iodide transport or utilization defect
Hypothyroidism
Iodotyrosine dehalogenase deficiency
TPO deficiencyn nd dysfunction
27
Defects in thyroglobulin synthesis

28. • ATROPHIC HYPOTHYROIDISM
Acquired
HASHIMOTOS DISEASE
Postablative due to 131 Iodine surgery
Congenital
Thyroid agenesis or dysplasia
TSH receptor defects
Thyroidal Gs protein abnormalities
Idiopathic TSH unresponsiveness
TRANSIENT HYPOTHYROIDISM 28
following subacute painless or postpartum thyroiditis

29. • CONSUMPTIVE HYPOTHYROIDISM
• hemangiomas ,hemangioendoheliomas
• CENTRAL HYPOTHYROIDISM
• Acquired
• pituatary origin
• hypothalamic disorders
• dopamine & or severe stress
• Congenital
• TSH deficiency/structural abnormality
• TSH receptor defect
• RESISTANCE TO THYROID HARMONE 29
• generalised or pituatary dominant

30. Multi system effects - Hypothyroidism
General Neuromuscular
•Lethargy, Somnalence •Aches and pains
•Weight gain, Goitre •Muscle stiffness
•Cold Intolerence •Carpel tunnel syndrome
Cardiovascular •Deafness, Hoarseness
•Bradycardia, Angina •Cerebellar ataxia
•CHF, Pericardial Effusion •Delayed DTR, Myotonia
•HyperlipIdemia, Xanthelsma •Depression, Psychosis
Haematological Gastro-intestinal
Iron def. Anaemia, •Constipation, Ileus, Ascites
Normo cytic /chromic Anaemia Dermatological
Reproductive system •Dry flaky skin and hair
•Infertility, Menorrhagia •Myxoedema, Malar flushes 30
•Impotence, Inc. Prolactin •Vitiligo, Carotenimia, Alopecia

31. Clinical Signs of Hypothyroidism
 Coarse Hair; Dry cool and pale skin
 Goitre (not in all cases), Hoarseness of voice
 Non-pitting oedema (myxoedema)
 Puffiness of eyes and face
 Delayed relaxation of DTR
 Slow hoarse speech and slow movements
 Thinning of lateral 1/3 of eye brows
 Bradycardia, pericardial effusion 31

32. Thyroid Failure - Organ Systems
Cardiovascular
• Decreased ventricular contractility
• Increased diastolic blood pressure
• Decreased heart rate
Central Nervous
• Decreased concentration
• General lack of interest
• Depression
Gastro-instestinal
• Decreased GI motility
• Constipation 32

33. Thyroid Failure - Organ Systems
Musculoskeletal
 Muscle stiffness, cramps, pain,
weakness, myalgia
 Slow muscle-stretch reflexes,
muscle enlargement, atrophy
Renal
 Fluid retention and oedema
 Decreased glomerular filtration 33

34. Thyroid Failure - Organ Systems
Reproductive
• Arrest of pubertal development
• Reduced growth velocity
• Menorrhagia, Amenorrhea
• Anovulation, Infertility
Hepatic
• Increased LDL / TC
• Elevated LDL + triglycerides
34

35. Thyroid Failure - Organ Systems
Skin and Hair
 Thickening and dryness of skin
 Dry, coarse hair, Alopecia
 Loss of scalp hair and / or
lateral eyebrow hair
35

36. HORMONAL EFFECTS ON THYROID FUNCTION
• Glucocorticoid Excess-decreased TSH,TBG,TTR
• Decreased serum T3/T4 and increase Rt3 production
• Decreased T4 and increased T3 in graves disease
• Deficiency-Increased TSH
• Estrogen-Increased TBG sialylation and half life in serum
• Increased TSH in post menopausal women
• Increased T4 requirement in hypothyroid patients
• Androgen-Decreased TBG
• Decreased T4 requirment in hypothyroid patient 36
• Growthhormone-Decreased D3 activity

37. 37
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38. Cassava Plant
Topiaco - Sago
(Javva Arisi)
38

39. Tapioca Root - Sago
Tapioca (tubers) Dried Tapioca - Sago
39

40. My xedema
40

41. My xedema
41

42. Co-morbidity
• Hypercholosterolemia
• Depression
• Infertility – Menstrual Irregularities
• Diabetes mellitus
42

43. Hypothyroidism and
Hypercholesterolemia
• 14% of patients with elevated cholesterol
have hypothyroidism
• Approximately 90% of patients with
overt hypothyroidism have increased
cholesterol and / or triglycerides
43

44. Lipids in Patient with Hypothyroidism
Hypercholesterolemia
(>200 mg/dL)
Hypertriglyceridemia
(>150 mg/dL)
Hypercholesterolemia
and mild Hyper TG
N= 268 Normal Lipids
44

45. Effect of Thyroxine therapy
on Hypercholesterolemia in
Patients with mild Thyroid failure
“The decrease in total cholesterol achieved with [Thyroxine
replacement] substitution therapy in patients with subclinical
hypothyroidism [mild thyroid failure] may be considered as an
important decrease in cardiovascular risk favouring treatment.”
45

46. Suspect Hypothyroidism
1. Amenorrhea
2. Oligomenorrhea
3. Menorrhogia
4. Galactorrhea
5. Premature ovarian failure
6. Infertility
7. Decreased libido
8. Precocious / delayed puberty
9. Chronic urticaria 46

47. 47

48. Algorithm for Hypothyroidism
Measure TSH
Elevated TSH Normal TSH
Measure FT4 Considering Pituitary
Normal Low No Yes
Sub-clinical hypo Primary hypothyroid No tests Measure FT4
TPO + TPO - TPO + TPO - Low Normal
T4 repl Annual FU Hashimoto Evaluate Pituitary
48
No tests
Sick Euthyroid
Others Drugs effect

49. Hormone
replacement
49

50. Treatment
• Goal : Normalize TSH level regardless of cause of
hypothyroidism
• Treatment : Once daily dosing with Levothyroxine sodium
(1.6µg/kg/day-1.8ug/kg/day)
• Monitor TSH levels at 6 to 8 weeks, after initiation of
therapy or dosage change
50

51. Treatment
• Treatment of choice is levothyroxin
• Not recommended for use :
 Desiccated thyroid extract
 Combination of thyroid hormones
 T3 replacement except in Myxedema coma
51

52. Dosage Adjustments
• Age (in elderly start with half dose)
• Severity and duration of hypothyroidism (↑ dose)
• Weight (0.5µg/kg/day ↑ upto 3.0µg/kg/day)
• Malabsorption (requires ↑ dose)
• Concomitant drug therapy (only on empty stomach)
• Pregnancy ( 25% -50%↑ in dose), safe in lactating
mother
• Presence of cardiac disease (start alt. day Rx) 52

53. Start Low and Go Slow
• Goal : normalize TSH level – 25, 50 and 100 mcg tablets avail.
• Starting dose for healthy patients < 50 years at 1.0 µg/kg/day
• Starting dose for healthy patients > 50 years should be < 50
µg/day. Dose ↑ by 25 µg, if needed, at 6 to 8 weeks intervals.
• Starting dose for patients with heart disease should be 12.5 to 25
µg/day and increase by 12.5 to 25 µg/day, if needed, at 6 to 8
weeks intervals
53

54. How the patient improves
 Feels better in 2 – 3 weeks
 Reduction in weight is the first improvement
 Facial puffiness then starts coming down
 Skin changes, hair changes take long time to regress
 TSH starts showing decrements from the high values
 TSH returns to normal eventually
54

55. Drug Interactions
• Malabsorption Syndromes  Drugs that affect metabolism
• Reduced Absorption  Rifampin
 Cholestyramine resin  Carbamazepine
 Sucralfate  Phenytoin
 Ferrous sulfate
 Phenobarbitol
 Soybean formula
 Aluminum hydroxide
 Amiodarone
 Colestipol hydrochloride
55

56. Inappropriate Dosage
Over-replacement risks
• Reduced bone density / osteoporosis
• Tachycardia, arrhythmia. atrial fibrillation
• In elderly or patients with heart disease, angina,
arrhythmia, or myocardial infarction2
Under-replacement risks
• Continued hypothyroid state
• Long-term end-organ effects of hypothyroidism
• Increased risk of hyperlipidemia 56

57. 20.2.98
Massive Pericardial Effusion in Hypo 57

58. 26.7.98
58
Clearing of Pericardial Effusion with Rx.

59. 14.9.99
Reappearance of Pericardial Effusion 59
after treatment is discontinued

60. • CENTRAL HYPOTHROIDISM
• AFTER SURGERY
FT4 evaluation 60

61. Diet in Iodine deficiency
• Iodized salt
• Selenium supplementation
• Avoid Cassava
• Avoid cabbage (goitrogens)
• Avoid formula milk
• Fish, meat, milk & eggs
61

62. Special
situations
62

63. My xedema Coma
• Precipitating factors :
 Infection, trauma, stroke, cardiovascular, hemorrhage drug
overdose, diuretics
• Signs and Symptoms :
 Mental confusion, hypothermia, bradycardia, older age,
 ↓ Na, ↓ glucose, ↑ CO2, ↓ WBC, ↓ Hct, ↑ CPK
 ↓ EKG voltage, myxedema, b-carotnenemia
• Treatment
Initial IV THYROXINE 500-800 mcg/day ,followed by daily dose of
I.V thyroxine 100 mcg thereafter ,alt I.V leothyronine 25mcg b.d
63

64. Sick Euthyroid Syndrome
 Total T3 reduced
 FT3 reduced
 Total T4 reduced
 FT4 Normal
 TSH Normal
 Clinically Euthyroid
64

65. • T3 -0.04nmo/l 0.93-2.33nmol/lit
• T4-59.70nmol/l 60-120 nmol/lit
• TSH-2.52IU/ml >7.0-hypothyroid
<0.2 hyperthyroid
Case-1 65

66. • T3 -1.42nmol/l
• T4-106.96nmol/l
• TSH-<0.05IU/ml
Case 2 66

67. The Commandments
 Highly suspect hypothyroidism  All obese patients TSH a must
 Growth and pubertal delay  For all pregnant -test TSH, FT4
 Unexplained depression  Postmenopausal 15% Hypothy
 TSH is the test in Hypothy.  Start low and go slow
 TSH, FT4 to confirm Dx.  Use Levothyroxine only
 Nine square magic  Always on empty stomach
 Test cord blood for TSH  Thyroxine - avoid empirical use
67

68. 68