Hypothyroidism by Dr Sarma

1
Knowledge is essential Applied, it is
Wisdom Wisdom is Happiness
2
Abnormal Thyroid Function A Practical Approach
3
Clinical Exam. of Thyroid

• 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
• Pembertons sign for RSG

4
Where to look for Thyroid ?
5
Clinical Anatomy of Thyroid
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Clinical Exam of Thyroid
7
Clinical Exam of Thyroid
8
Thyromegaly
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Thyroid Gland
Hormonogenesis
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Thyroid Regulation
TSH -R
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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

12
Metabolism of Thyroid Hormones
Thyroid Gland
100 nm
Thyroxine FT4
5 nm
lt 5 nm
45 nm
35 nm
Reverse T3 (rT3)
Triiodothyronine (FT3)
20 nm
Tertrac etc.,
13
What happens in Fluorosis
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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

15
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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Thyroid Function Tests

1. TSH
2. Free T4
3. Free T3
4. Anti-Thyroid Antibodies
5. Nuclear Scintigraphy
6. FNAC of nodule

18
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
• Dont order for Total T4 or Total T3
• Never order RIU in pregnancy or lactation

19
Which Lab to choose ?

• Depends on the method of estimation of hormones
• Equilibrium Dialysis is the gold Standard for TSH
• Radio-immuno assay - 3rd or 4th gen. RIA is the
  best
• Reliability of ELISA is not adequate
• 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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BASIC THYROID EVALUATION



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



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



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



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



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



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



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



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



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



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



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



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



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



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



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



SECONDARY HYPERTHYROID
LOW NORMAL HIGH
FREE THYROXINE or FT4
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
38
BASIC THYROID EVALUATION



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



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



LOW NORMAL HIGH
FREE THYROXINE or FT4
NON THYROID ILLNESS or NTI
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
41
BASIC THYROID EVALUATION



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



NTI or Pt. on ELTROXIN
SECONDARY HYPERTHYROID
PRIMARY HYPERTHYROID
SUB-CLINICAL HYPERTHYROID
SUB-CLINICAL HYPOTHYROID
LOW NORMAL HIGH
FREE THYROXINE or FT4
EUTHYROID
SECONDARY HYPOTHYROID
PRIMARY HYPOTHYROID
NON THYROID ILLNESS - NTI
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

Moderate
Severe
Mild
Normal Range
Free T3
Free T4
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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 Reidles
  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.

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General Considerations
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Hypothyroidism

• Epidemiology
• Most common endocrine disease
• Females gt 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

• Primary contd..
• 3. Post Ablative
• - Permanent
• - Transient
• - Sub-clinical
• 4. Congenital
• B. Secondary / Central
• Pituitary/ hypothalamic

• A. Primary
• 1. Enlarged Thyroid
• - Hashimotos (65)
• - Iodine Deficiency (25)
• - Drug-induced (Lithium)
• - Dysharmonogenesis
• 2. Normal Thyroid
• - Spontaneous Atrophic

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IDD
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Clinical considerations
54
Disease Burden

1. 5 of the general population are Sub-clinically
   Hypothyroid
2. 15 of all women gt 65 yrs. are hypothyroid
3. 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
4. All persons aged above 60 years Order for TSH

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Multi system effects - Hypothyroidism

• 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

• 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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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
• Elderly women / men
• Hypercholesterolemia
• Lithium, Amiodarone
• Postpartum women

• Other Autoimmune disease
• Rx. Graves Ophthalmopathy
• Family H/o thyroid disease
• Neck irradiation therapy
• Previous Rx for thyrotoxicosis
• Autoimmune Thyroiditis

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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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(No Transcript)
65
Endemic Goiter
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Urine Iodine Conc. lt 50 µg/L
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(No Transcript)
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Myxedema
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Macroglossia
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Xanthomata
Tuberous Xanthoma
Xanthelasma
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Solid Oedema
Xanthomata
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Myxoedema with Carotineamia
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Recovery after L-Thyroxine
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Pituitary Tumor Secondary Hypo
Normal Pituitary Fossa
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26.7.98
Clearing of Pericardial Effusion with Rx.
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14.9.99
Reappearance of Pericardial Effusion after
treatment is discontinued
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Co-morbidity

• Hypercholosterolemia
• Depression
• Infertility Menstrual Irregularities
• Diabetes mellitus

78
Hypothyroidism and Hypercholesterolemia

• 14 of patients with elevated cholesterol have
  hypothyroidism
• Approximately 90 of patients with overt
  hypothyroidism have increased cholesterol and /
  or triglycerides

79
Lipids in Patient with Hypothyroidism

• Hypercholesterolemia(gt200 mg/dL)
• Hypertriglyceridemia(gt150 mg/dL)
• Hypercholesterolemia and mild Hyper TG
• Normal Lipids

N 268
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LDL-C Levels Increase With Increasing
Hypothyroidism Grade
246
191
168
144
137
133
LDL-C(mg/dL
C
1
2
3
4
5
Hypothyroidism Grade
Basal TSH (mU/L) 1.1 3.0 8.6
22.7 44.4 63.7
81
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.

82
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

83
Hypothyroidism and Depression

• Depression

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
Sleep decreaseSuicidal ideation Weight change
Delusions
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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

85
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. Amenorrhea
2. Oligomenorrhea
3. Menorrhogia
4. Galactorrhea
5. Premature ovarian failure
6. Infertility
7. Decreased libido
8. Precocious / delayed puberty
9. Chronic urticaria

87
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

88
Algorithm for Hypothyroidism
89
Algorithm for Hypothyroidism
Measure TSH
Elevated TSH
Normal TSH
Measure FT4
Considering Pituitary
Normal
Low
No
Yes
No tests
Sub-clinical hypo
Primary hypothyroid
Measure FT4
TPO -
TPO
TPO
TPO -
Low
Normal
Evaluate Pituitary Sick Euthyroid Drugs effect
Hashimoto
T4 repl
Annual FU
No tests
Others
90
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

92
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

93
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)

94
Start Low and Go Slow

• Goal normalize TSH level 25, 50 and 100 mcg
  tablets avail.
• Starting dose for healthy patients lt 50 years at
  1.0 µg/kg/day
• Starting dose for healthy patients gt 50 years
  should be lt 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

95
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

96
Drug Interactions

• Drugs that affect metabolism
• Rifampin
• Carbamazepine
• Phenytoin
• Phenobarbitol
• Amiodarone

• Malabsorption Syndromes
• Reduced Absorption
• Cholestyramine resin
• Sucralfate
• Ferrous sulfate
• Soybean formula
• Aluminum hydroxide
• Colestipol hydrochloride

97
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

98
Diet in Iodine deficiency

• Iodized salt
• Selenium supplementation
• Avoid Cassava
• Avoid cabbage (goitrogens)
• Avoid formula milk
• Fish, meat, milk eggs

99
Special situations
100
Sub-clinical Hypothyroidism

• Chronic autoimmune thyroiditis
• Graves hyperthyroidism with radioiodine, surgery
• Inadequate replacement therapy for hypothyroidism
• Lithium carbonate therapy (for depressive illness)

101
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
  Hashimotos disease and Graves disease

102
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
• ICU transfer, T3 100 µg IV sixth hourly, 500 µg
  of T4 , antibiotics, ventilation, hydrocortisone
  IV, passive warming, careful volume management

103
Sick Euthyroid Syndrome

• Total T3 reduced
• FT3 reduced
• Total T4 reduced
• FT4 Normal
• TSH Normal
• Clinically Euthyroid

104
The Commandments
105
The Commandments

• All obese patients TSH a must
• For all pregnant -test TSH, FT4
• Postmenopausal 15 Hypothy
• Start low and go slow
• Use Levothyroxine only
• Always on empty stomach
• Thyroxine - avoid empirical use

• Highly suspect hypothyroidism
• Growth and pubertal delay
• Unexplained depression
• TSH is the test in Hypothy.
• TSH, FT4 to confirm Dx.
• Nine square magic
• Test cord blood for TSH

106
Question 1

• Should a serum TSH be a routine component of the
  periodic health exam in women?

107
Question 2

• What is the appropriate biochemical end point for
  adequate thyroid hormone replacement in
  hypothyroid patient?

108
Question 3

• Are there risks associated with over replacement?

109
Question 4

• Are all L-thyroxine products therapeutically
  equivalent? Should combination T4/T3 preparations
  be used?

110
Question 5

• What is the impact of pregnancy on Thyroxine
  replacement therapy in a hypothyroid women?

111
Question 6

• What is the impact of breast feeding on the
  management of maternal hypo and hyperthyroidism?

112
Question 7

• Should women with sub-clinical hypothyroidism be
  treated with L-Thyroxine?

113
Question 8

• Should euthyroid patient with benign thyroid
  nodules be placed on thyroid hormone suppression
  therapy?