www.drsarma.in 1 knowledge is essential applied, it is wisdom wisdom is happiness
TRANSCRIPT
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Knowledge is essential
Applied, it is Wisdom
Wisdom is Happiness
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Charaka SamhitaCharaka Samhita
Sukham Samagram Vijnane Vimale cha Pratishthitam
All happiness is rooted in the
Good Science
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Dr.R.V.S.N.Sarma., M.D., M.Sc.,
Consultant Physician and Chest Specialist
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Some interesting casesSome interesting cases1. Govindammal – Persistant diarrhea2. Sridhar – HM – Cachexia 70 kg to 40 kg 3. Kavitha – Weight loss – lung shadow 4. Sulochana – Severe anaemia – CHF5. Lady doctor – listlessness – anaemia6. Kamatchi – Infertility after 16 yrs of ML7. Siva – Atrial fibrillation – cachexia8. Begum - Our staff member – weight loss9. John – 32 yrs. Premature IHD10. Kadirvelu – severe diabetes 11. Annaji – dyspnea – tracheal compression
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Clinical Exam. of ThyroidClinical 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 Pemberton’s sign for RSG
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Where to look for Thyroid ?Where to look for Thyroid ?
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Clinical Anatomy of ThyroidClinical Anatomy of Thyroid
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Clinical Exam of ThyroidClinical Exam of Thyroid
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Clinical Exam of ThyroidClinical Exam of Thyroid
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Clinical Exam of ThyroidClinical Exam of Thyroid
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ThyromegalyThyromegaly
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Thyroid Regulation
PLASMA T4 + FT4
HYPOTHALAMUS - TRH
ANT. PITUITARY - TSH
THYROID T4 and T3
PLASMA T3 + FT3
TISSUES FT4 to FT3, rT3
TSH -R
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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
Thyroxine FT4
Reverse T3 (rT3) Triiodothyronine (FT3)
Tertrac etc.,
100 nm
5 nm< 5 nm45 nm 35 nm
20 nm
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What happens in Fluorosis
Normal catabolism -Thyroxine FT4 FT3
rT3 will be LOWrT3 ÷ T3 ratio will be LOWNormal deiodination of T4
rT3
Abnormal catabolism -Thyroxine FT4 FT3
rT3 will be HIGHrT3 ÷ T3 ratio will be HIGHFluoride affects the normaldeiodination of T4
rT3
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The Thyronines
Mono Iodo Tyrosine – MIT Di Iodo Tyrosine – DITTri 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 measuredOnly 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 glandFrom the thyroid gland
- 80% of hormone secreted is T4
- 20% of hormone secreted is T3
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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
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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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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
Which Lab to choose ?
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How to interpret How to interpret results ?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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LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
LO
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N
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HIG
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FR
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HY
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BASIC THYROID EVALUATION
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LO
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EUTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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HIG
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PRIMARYHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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4 PRIMARYHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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SECONDARYHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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N
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HIG
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SECONDARYHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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SUB-CLINICALHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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SUB-CLINICALHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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L
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FR
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NON THYROIDILLNESS or NTI
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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NTI or Pt.on ELTROXIN
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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EUTHYROIDSUB-CLINICAL
HYPERTHYROID
NON THYROIDILLNESS - NTI
NTI or Pt.on ELTROXIN
SUB-CLINICALHYPOTHYROID
SECONDARYHYPERTHYROID
SECONDARYHYPOTHYROID
PRIMARYHYPERTHYROID
PRIMARYHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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EUTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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PRIMARYHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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4 PRIMARYHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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SECONDARYHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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SECONDARYHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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SUB-CLINICALHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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SUB-CLINICALHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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L
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FR
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NON THYROIDILLNESS or NTI
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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NTI or Pt.on ELTROXIN
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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LO
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EUTHYROIDSUB-CLINICAL
HYPERTHYROID
NON THYROIDILLNESS - NTI
NTI or Pt.on ELTROXIN
SUB-CLINICALHYPOTHYROID
SECONDARYHYPERTHYROID
SECONDARYHYPOTHYROID
PRIMARYHYPERTHYROID
PRIMARYHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
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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 SevereMild
Normal Range
Free T4
Free T3
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Nucleotide Scintigraphy
I 123 and TC 99m Radio Nucleotide ScintigraphyThis test is not at all required in hypothyroidismThis is only to confirm a hyper functioning thyroid orTo assess whether a nodule is ‘hot’ or ‘cold’Never order for this test for hypothyroidismSimilar 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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Current Trends in Dx. and Rx.
HYPOTHYROIDISMHYPOTHYROIDISM
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General ConsiderationsGeneral Considerations
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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
Hypothyroidism
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ClassificationClassification
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Classification of Hypothyroidism
Primary contd..3. Post Ablative
- Permanent- Transient- Sub-clinical
4. CongenitalB. Secondary / Central
Pituitary/ hypothalamic
A. Primary1. Enlarged Thyroid
- Hashimoto’s (65%)- Iodine Deficiency (25%)- Drug-induced (Lithium)- Dysharmonogenesis
2. Normal Thyroid- Spontaneous Atrophic
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IDDIDD
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Clinical considerationsClinical considerations
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Disease Burden
1. 5% of the general population are Sub-clinically Hypothyroid
2. 15 % of all women > 65 yrs. are hypothyroid3. 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
General•Lethargy, Somnalence•Weight gain, Goitre•Cold IntolerenceCardiovascular•Bradycardia, Angina•CHF, Pericardial Effusion•HyperlipIdemia, XanthelsmaHaematologicalIron def. Anaemia, Normo cytic /chromic AnaemiaReproductive system•Infertility, Menorrhagia•Impotence, Inc. Prolactin
Neuromuscular•Aches and pains•Muscle stiffness•Carpel tunnel syndrome•Deafness, Hoarseness•Cerebellar ataxia•Delayed DTR, Myotonia•Depression, PsychosisGastro-intestinal•Constipation, Ileus, AscitesDermatological•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 !!
Psychiatric patients
Elderly women / men
Patients of OSA
Hypercholesterolemia
Lithium, Amiodarone
Postpartum women
Other Autoimmune disease
Rx. Grave’s Ophthalmopathy
Family H/o thyroid disease
Neck irradiation therapy
Previous Rx for thyrotoxicosis
Autoimmune Thyroiditis
Order for TSH alone as a screen
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Thyroid Failure - Organ Systems
Cardiovascular• Decreased ventricular contractility• Increased diastolic blood pressure• Decreased heart rateCentral Nervous• Decreased concentration• General lack of interest• DepressionGastro-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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Reproductive Arrest of pubertal development Reduced growth velocity Menorrhagia, Amenorrhea Anovulation, Infertility
Hepatic Increased LDL / TC Elevated LDL + triglycerides
Thyroid Failure - Organ Systems
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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 PhotographsClinical Photographs
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Congenital HypothyroidismCongenital Hypothyroidism
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Endemic GoiterEndemic Goiter
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Urine Iodine Conc. < 50 µg/L
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Topiaco - Sago (Javva Arisi)
Cassava PlantCassava Plant
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Tapioca Root - SagoTapioca Root - Sago
Tapioca (tubers) Dried Tapioca - Sago
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MyxedemaMyxedema
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MyxedemaMyxedema
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MacroglossiaMacroglossia
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XanthomataXanthomata
Xanthelasma
Tuberous Xanthoma
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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 HypoNormal Pituitary Fossa
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Massive Pericardial Effusion in Hypo
20.2.98
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Clearing of Pericardial Effusion with Rx.
26.7.98
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Reappearance of Pericardial Effusion after treatment is discontinued
14.9.99
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Co-morbidity
HypercholosterolemiaDepressionInfertility – Menstrual IrregularitiesDiabetes 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
Normal LipidsN= 268
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LDL-C Levels Increase With Increasing Hypothyroidism Grade
0
50
100
150
200
250
CC 11 22 33 4*4* 5†5†
144144 133133 137137
168168
191191
246246L
DL
-C(m
g/dL
LD
L-C
(mg/
dL
Basal TSH (mU/L) 1.1 3.0 8.6 22.7 44.4 63.7
Hypothyroidism Grade
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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 Hypothyroidism
Sleep decreaseSuicidal ideation Weight change Delusions
ConstipationDecreased Conc.Decreased libidoDepressed moodDiminished interestWeight increaseFatigue
BradycardiaCardiac and lipid AbnormalitiesCold intoleranceHair and skin changesDelayed reflexesGoiter
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Thyroxine in Depression
1. Thyroxine therapy is recommended for patients with depression who have persistently elevated serum TSH2. Antidepressants may be less effective if thyroid function not normalized
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Hypothyroidism and Infertility
1. Hypothyroidism associated with infertility, miscarriage, stillbirth2. Infertility : Evaluate thyroid function, treat hypothyroidism3. Equivocal results: Begin therapy; discontinue if no pregnancy for several months.
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Suspect Hypothyroidism
1. Amenorrhea2. Oligomenorrhea3. Menorrhogia4. Galactorrhea5. Premature ovarian failure6. Infertility7. Decreased libido8. Precocious / delayed puberty9. 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 No Yes
Sub-clinical hypo
TPO + TPO -
T4 repl Annual FU
Primary hypothyroid
TPO + TPO -
No tests Measure FT4
Low Normal
No testsEvaluate PituitarySick EuthyroidDrugs effect
Hashimoto
Others
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Hormone replacementHormone 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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Treatment of choice is levothyroxin Branded thyroxine recommended Brand consistency recommended No divided doses - illogical Not recommended for use :
Desiccated thyroid extractCombination of thyroid hormones
T3 replacement except in Myxedema coma
Many Causes, One Treatment
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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)
Dosage Adjustments
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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
Start Low and Go Slow
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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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Malabsorption Syndromes Reduced Absorption
Cholestyramine resinSucralfateFerrous sulfateSoybean formulaAluminum hydroxideColestipol hydrochloride
Drugs that affect metabolismRifampin
Carbamazepine
Phenytoin
Phenobarbitol
Amiodarone
Drug Interactions
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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
Inappropriate Dosage
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Diet in Iodine deficiencyDiet in Iodine deficiency
Iodized saltSelenium supplementationAvoid CassavaAvoid cabbage (goitrogens)Avoid formula milkFish, meat, milk & eggs
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Special situationsSpecial 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 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
Total T3 reduced FT3 reducedTotal T4 reducedFT4 NormalTSH NormalClinically Euthyroid
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The CommandmentsThe Commandments
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The Commandments
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
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
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Question # 1Question # 1
Should a serum TSH be a
routine component of
the periodic health
exam in women?
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Question # 2Question # 2
What is the appropriate
biochemical end point for
adequate thyroid hormone
replacement in
hypothyroid patient?
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Question # 3Question # 3
Are there risks
associated with over
replacement?
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Question # 4Question # 4
Are all L-thyroxine products
therapeutically
equivalent? Should
combination T4/T3
preparations be used?
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Question # 5Question # 5
What is the impact of
pregnancy on Thyroxine
replacement therapy in
a hypothyroid women?
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Question # 6Question # 6
What is the impact of
breast feeding on the
management of maternal
hypo and
hyperthyroidism?
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Question # 7Question # 7
Should women with sub-
clinical hypothyroidism
be treated with L-
Thyroxine?
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Question # 8Question # 8
Should euthyroid patient
with benign thyroid
nodules be placed on
thyroid hormone
suppression therapy?
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We need to apply the current knowledge
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