Knowledge is essential
Applied, it is Wisdom
Wisdom is Happiness
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1
Charaka Samhita
Sukham Samagram Vijnane
Vimale cha Pratishthitam
All happiness is rooted
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in
the Good Science
2
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Dr.R.V.S.N.Sarma., M.D., M.Sc.,
Consultant Physician and Chest Specialist
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3
Some interesting cases
1. Govindammal – Persistant diarrhea
2. Sridhar – HM – Cachexia 70 kg to 40 kg
3. Kavitha – Weight loss – lung shadow
4. Sulochana – Severe anaemia – CHF
5. Lady doctor – listlessness – anaemia
6. Kamatchi – Infertility after 16 yrs of ML
7. Siva – Atrial fibrillation – cachexia
8. Begum - Our staff member – weight loss
9. John – 32 yrs. Premature IHD
10. Kadirvelu – severe diabetes
www.drsarma.in 11. Annaji – dyspnea – tracheal compression
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Clinical Exam. of Thyroid
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
Have patient seated on a stool / chair

Inspect neck – also while drinking water

Examine with neck in relaxed position

Palpate from behind the patient

Remember the rule of finger tips

Use the tips of fingers for palpation

Palpate firmly down to trachea

Pemberton’s sign for RSG
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Where to look for Thyroid ?
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Clinical Anatomy of Thyroid
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Clinical Exam of Thyroid
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Clinical Exam of Thyroid
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Clinical Exam of Thyroid
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Thyromegaly
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Thyroid Regulation
HYPOTHALAMUS - TRH
ANT. PITUITARY - TSH
TSH -R
THYROID T4 and T3
PLASMA T4 + FT4
PLASMA T3 + FT3
TISSUES FT4 to FT3, rT3
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In the Thyroid Gland
There the following 5 steps in the hormonogenesis
1.
Trapping of inorganic Iodine from dietary Iodides
2.
Activation of Iodine to high valance I2
3.
Incorporation of I2 into Tyrosine of Thyroid Globulin
4.
Coupling of formed MIT and DIT to form T4 & T3
5.
Proteolysis of Thyroglobulin to release T4 & T3
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Metabolism of Thyroid Hormones
Thyroid Gland
100 nm
Thyroxine FT4
< 5 nm
Reverse T3 (rT3)
45 nm 35 nm
5 nm
Triiodothyronine (FT3)
20 nm
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Tertrac etc.,
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What happens in Fluorosis
Normal catabolism -Thyroxine
FT4
FT3
rT3
rT3 will be LOW
rT3 ÷ T3 ratio will be LOW
Normal deiodination of T4
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Abnormal catabolism -Thyroxine
FT4
FT3
rT3
rT3 will be HIGH
rT3 ÷ T3 ratio will be HIGH
Fluoride affects the normal
deiodination of T4
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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
Only Free T4 and Free T3 are metabolically active
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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
- 20% of hormone secreted is T3
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Thyroid Function Tests
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1.
TSH
2.
Free T4
3.
Free T3
4.
Anti-Thyroid Antibodies
5.
Nuclear Scintigraphy
6.
FNAC of nodule
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What tests should I order ?
As per the Guidelines of the AACE and ATA, ITS
1. TSH alone if Hypothyroidism is suspected
2. TSH and Free T4 only if Hyperthyroidism is
suspected or for routine evaluation
3. Free T3 if T3 toxicosis is suspected
4. For follow-up of treatment only TSH
5. Don’t order for Total T4 or Total T3
6. Never order RIU in pregnancy or lactation
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Which Lab to choose ?
1.
Depends on the method of estimation of hormones
2.
Equilibrium Dialysis is the gold Standard for TSH
3.
Radio-immuno assay - 3rd or 4th gen. RIA is the best
4.
Reliability of ELISA is not adequate
5.
Chemiluminescence immuno assay - CIA is the gold
standard for FT4 but expensive and less widely available
Choose a lab which offers 3rd or 4th generation RIA method
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How to interpret results ?
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The Nine Square Game
To evaluate our Thyroid patient
As per the AACE and ITS Guidelines
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
EUTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
PRIMARY
HYPOTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
PRIMARY
HYPERTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
SECONDARY
HYPOTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
SECONDARY
HYPERTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
SUB-CLINICAL
HYPERTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
SUB-CLINICAL
HYPOTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
NON THYROID
ILLNESS or NTI
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
NTI or Pt.
on ELTROXIN
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
PRIMARY
NTI or Pt.
SECONDARY
HYPERTHYROID on ELTROXIN HYPERTHYROID
SUB-CLINICAL
EUTHYROID
HYPERTHYROID
SUB-CLINICAL
HYPOTHYROID
SECONDARY NON THYROID
PRIMARY
HYPOTHYROID ILLNESS - NTI HYPOTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
EUTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
PRIMARY
HYPOTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
PRIMARY
HYPERTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
SECONDARY
HYPOTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
SECONDARY
HYPERTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
SUB-CLINICAL
HYPERTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
SUB-CLINICAL
HYPOTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
NON THYROID
ILLNESS or NTI
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
NTI or Pt.
on ELTROXIN
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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FREE THYROXINE or FT4
BASIC THYROID EVALUATION
PRIMARY
NTI or Pt.
SECONDARY
HYPERTHYROID on ELTROXIN HYPERTHYROID
SUB-CLINICAL
EUTHYROID
HYPERTHYROID
SUB-CLINICAL
HYPOTHYROID
SECONDARY NON THYROID
PRIMARY
HYPOTHYROID ILLNESS - NTI HYPOTHYROID
LOW
NORMAL
HIGH
THYROID STIMULATING HORMONE - TSH
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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
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T.F.T. in Progressive Hypothyroidism
TSH
Mild
Moderate
Severe
Normal Range
Free T4
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Free T3
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Nucleotide Scintigraphy
 I 123 and TC 99m Radio Nucleotide Scintigraphy

This test is not at all required in hypothyroidism

This is only to confirm a hyper functioning thyroid or

To assess whether a nodule is ‘hot’ or ‘cold’

Never order for this test for hypothyroidism

Similar is the case with FNAC – in hypothyroid goiter

If TSH is high and FT4 is low there is no role for FNAC
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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
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HYPOTHYROIDISM
Current Trends in Dx. and Rx.
Dr.Sarma@works
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General Considerations
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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
– In clear cut cases - typical signs and symptoms
– Low free T4 and High TSH
– Easily treatable with oral Levo-thyroxine
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Classification
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Classification of Hypothyroidism
A. Primary
1. Enlarged Thyroid
Primary contd..
3. Post Ablative
- Permanent
- Hashimoto’s (65%)
- Transient
- Iodine Deficiency (25%)
- Sub-clinical
- Drug-induced (Lithium)
- Dysharmonogenesis
4. Congenital
2. Normal Thyroid
- Spontaneous Atrophic
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B. Secondary / Central
Pituitary/ hypothalamic
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IDD
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Clinical considerations
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Disease Burden
1.
2.
3.
4.
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 TSH
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Multi system effects - Hypothyroidism
General
•Lethargy, Somnalence
•Weight gain, Goitre
•Cold Intolerence
Cardiovascular
•Bradycardia, Angina
•CHF, Pericardial Effusion
•HyperlipIdemia, Xanthelsma
Haematological
Iron def. Anaemia,
Normo cytic /chromic Anaemia
Reproductive system
•Infertility, Menorrhagia
•Impotence, Inc. Prolactin
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Neuromuscular
•Aches and pains
•Muscle stiffness
•Carpel tunnel syndrome
•Deafness, Hoarseness
•Cerebellar ataxia
•Delayed DTR, Myotonia
•Depression, Psychosis
Gastro-intestinal
•Constipation, Ileus, Ascites
Dermatological
•Dry flaky skin and hair
•Myxoedema, Malar flushes
•Vitiligo, Carotenimia, Alopecia
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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
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What the mind knows the eyes see !!
Order for TSH alone as a screen
 Psychiatric patients
 Other Autoimmune
 Elderly women / men
 Rx. Grave’s Ophthalmopathy
 Patients of OSA
 Family H/o thyroid disease
 Hypercholesterolemia
 Neck irradiation therapy
 Lithium, Amiodarone
 Previous Rx for thyrotoxicosis
 Postpartum women
 Autoimmune Thyroiditis
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disease
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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
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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
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Thyroid Failure - Organ Systems
Reproductive
Arrest of pubertal development
 Reduced growth velocity
 Menorrhagia, Amenorrhea
 Anovulation, Infertility

Hepatic

Increased LDL / TC

Elevated LDL + triglycerides
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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
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Clinical Photographs
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Congenital Hypothyroidism
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Endemic Goiter
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Urine Iodine Conc. < 50 µg/L
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Cassava Plant
Topiaco - Sago
(Javva Arisi)
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Tapioca Root - Sago
Tapioca (tubers)
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Dried Tapioca - Sago
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Myxedema
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Myxedema
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Macroglossia
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Xanthomata
Tuberous Xanthoma
Xanthelasma
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Solid Oedema
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Xanthomata
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Myxoedema with Carotineamia
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Recovery after L-Thyroxine
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Normal Pituitary Fossa
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Pituitary Tumor – Secondary Hypo
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20.2.98
Massive Pericardial Effusion in Hypo
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26.7.98
Clearing of Pericardial Effusion with Rx.
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14.9.99
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Reappearance of Pericardial Effusion
after treatment is discontinued
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Co-morbidity

Hypercholosterolemia

Depression

Infertility – Menstrual Irregularities

Diabetes mellitus
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Hypothyroidism and
Hypercholesterolemia
 14% of patients with elevated
cholesterol have hypothyroidism
 Approximately 90% of patients with
overt hypothyroidism have increased
cholesterol and / or triglycerides
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Lipids in Patient with Hypothyroidism
Hypercholesterolemia
(>200 mg/dL)
Hypertriglyceridemia
(>150 mg/dL)
Hypercholesterolemia
and mild Hyper TG
N= 268
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Normal Lipids
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LDL-C Levels Increase With
Increasing Hypothyroidism Grade
246
250
191
200
168
133
137
C
1
2
Basal TSH (mU/L) 1.1
3.0
8.6
LDL-C
(mg/dL
144
150
100
50
0
Hypothyroidism Grade
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3
4*
22.7 44.4
5†
63.7
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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.”
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Hypothyroidism and Depression
Depressive symptoms are common in
hypothyroidism
 Many hypothyroid patients fulfill DSM-IV
criteria for a depressive disorder
 Depressed patients may be more likely than
normal individuals to be hypothyroid
 All depressed patients should be evaluated
for thyroid dysfunction

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Hypothyroidism and Depression
Depression
Sleep decrease
Suicidal ideation
Weight change
Delusions
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Hypothyroidism
Constipation
Decreased Conc.
Decreased libido
Depressed mood
Diminished interest
Weight increase
Fatigue
Bradycardia
Cardiac and lipid
Abnormalities
Cold intolerance
Hair and skin changes
Delayed reflexes
Goiter
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Thyroxine in Depression
1. Thyroxine therapy is recommended for
patients with depression who have
persistently elevated serum TSH
2. Antidepressants may be less effective if
thyroid function not normalized
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Hypothyroidism and Infertility
1. Hypothyroidism associated with infertility,
miscarriage, stillbirth
2. Infertility : Evaluate thyroid function, treat
hypothyroidism
3. Equivocal results: Begin therapy; discontinue
if no pregnancy for several months.
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Suspect Hypothyroidism
1.
2.
3.
4.
5.
6.
7.
8.
9.
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Amenorrhea
Oligomenorrhea
Menorrhogia
Galactorrhea
Premature ovarian failure
Infertility
Decreased libido
Precocious / delayed puberty
Chronic urticaria
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Hypothyroidism and Diabetes
1.
Approximately 10% of patients with
type 1 diabetes mellitus develop
sub-clinical hypothyroidism
2.
In diabetic patients - examine for goitre
3.
TSH measurement at regular intervals
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Algorithm for Hypothyroidism
Measure TSH
Elevated TSH
Normal TSH
Measure FT4
Considering Pituitary
Normal
Low
Sub-clinical hypo
Yes
Primary hypothyroid
No tests
TPO -
Low
TPO +
TPO -
T4 repl
Annual FU
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No
TPO +
Hashimoto
Others
Evaluate Pituitary
Sick Euthyroid
Drugs effect
Measure FT4
Normal
No tests
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Hormone replacement
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Many Causes, One Treatment

Goal : Normalize TSH level regardless of
cause of hypothyroidism

Treatment : Once daily dosing with
Levothyroxine sodium (1.6µg/kg/day)
this comes to 100 mcg per day

Monitor TSH levels at 6 to 8 weeks, after
initiation of therapy or dosage change
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Many Causes, One Treatment

Treatment of choice is levothyroxin

Branded thyroxine recommended

Brand consistency recommended

No divided doses - illogical

Not recommended for use :
 Desiccated thyroid extract
 Combination of thyroid hormones
 T3 replacement except in Myxedema coma
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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% ↑ in dose), safe in lactating mother

Presence of cardiac disease (start alt. day Rx)
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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
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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
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Drug Interactions

Malabsorption Syndromes

Reduced Absorption

Cholestyramine resin

Sucralfate

Ferrous sulfate

Soybean formula

Aluminum hydroxide

Colestipol hydrochloride
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
Drugs that affect metabolism

Rifampin

Carbamazepine

Phenytoin

Phenobarbitol

Amiodarone
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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
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Diet in Iodine deficiency
 Iodized salt
 Selenium supplementation
 Avoid Cassava
 Avoid cabbage (goitrogens)
 Avoid formula milk
 Fish, meat, milk & eggs
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Special situations
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Sub-clinical Hypothyroidism

Chronic autoimmune thyroiditis

Graves’ hyperthyroidism with radioiodine, surgery

Inadequate replacement therapy for hypothyroidism

Lithium carbonate therapy (for depressive illness)
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Post-Partum Thyroiditis (PPT)
Definition

Occurrence of hyperthyroidism and / or
hypothyroidism during the postpartum period in
women who were euthryroid during pregnancy
At Highest Risk

Patients with type 1 diabetes, previous history of
PPT or other autoimmune disease such as
Hashimoto’s disease and Graves’ disease
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Myxedema 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

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ICU transfer, T3 100 µg IV sixth hourly, 500 µg of T4 ,
antibiotics, ventilation, hydrocortisone IV, passive warming,
careful volume management
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Sick Euthyroid Syndrome
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
Total T3 reduced

FT3 reduced

Total T4 reduced

FT4 Normal

TSH Normal

Clinically Euthyroid
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The Commandments
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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
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Question # 1
Should a serum TSH be a routine
component of the periodic
health exam in women?
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Question # 2
What is the appropriate biochemical
end point for adequate thyroid
hormone replacement in
hypothyroid patient?
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Question # 3
Are there risks associated with
over replacement?
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Question # 4
Are all L-thyroxine products
therapeutically equivalent?
Should combination T4/T3
preparations be used?
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Question # 5
What is the impact of pregnancy
on Thyroxine replacement
therapy in a hypothyroid
women?
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Question # 6
What is the impact of breast
feeding on the management
of maternal hypo and
hyperthyroidism?
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Question # 7
Should women with sub-clinical
hypothyroidism be treated with
L-Thyroxine?
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121
Question # 8
Should euthyroid patient with
benign thyroid nodules be
placed on thyroid hormone
suppression therapy?
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122
We need to apply the current knowledge
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