Thyroid physiology & Hypothyroidism
Post on 22-Apr-2015
2512 Views
Preview:
DESCRIPTION
Transcript
A CASE PROFILE OF THYROID
DISEASE
1
- Dr.Mohammed Siraj
- Dr.Parvez Khan
- Dr.Mohammed Sadiq Azam
- Dr.Praneetha Gayathri
THYROID GLAND HORMONOGENESIS
2
Thyroid Regulation
3
PLASMA T4 + FT4
HYPOTHALAMUS - TRH
ANT. PITUITARY - TSH
THYROID T4 and T3
PLASMA T3 + FT3
TISSUES FT4 to FT3, rT3
TSH -R
www.drsarma.in
4
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 & T35
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
6
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 glandFrom the thyroid gland
- 80% of hormone secreted is T4
- 20% of hormone secreted is T3
Throid hormones in peripheral tissues
• Plasma transport by
thyroxine binding globulin TBG -75 -80%bound
• Transthyretin 10-15%
• Albumin 5-10%
8
9
Thyroid Function Tests
1. TSH
2. Free T4
3. Free T3
4. Anti-Thyroid Antibodies
5. Nuclear Scintigraphy
6. FNAC of nodule10
11 LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
BASIC THYROID EVALUATION
12
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
EUTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
13
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
PRIMARYHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
14
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4 PRIMARYHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
15
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
SECONDARYHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
16
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
SECONDARYHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
17
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
SUB-CLINICALHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
18
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
SUB-CLINICALHYPOTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
19
L
OW
N
OR
MA
L
H
IGH
FR
EE
T
HY
RO
XIN
E
or
FT
4
NON THYROIDILLNESS or NTI
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
20
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
NTI or Pt.on ELTROXIN
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
21
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
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
THYROID HORMONES
TEST REFERENCE RANGE
TSH Normal Range 0.3 - 4.0 mU/L
Free T4 Normal Range 0.7-2.1 ng/dL
22TSH upper limit will soon be revised to 2.5 mU/L
Thyroid Antibodies
• Anti Microsomal (TM ) Antibodies• Anti Thyroglobulin (TG) Antibodies• Anti Thyroxine Per Oxidase (TPO) Ab.• Anti Thyroxine antibodies• Thyroid Stimulating (TSA) Antibodies
23
High titres TPO Ab in Hashimotos & Reidle’s thyroiditis Anti thyroxine Ab in peripheral resistance to Thyroxine TSA (TSI) in Graves’ Hyperthyroidism
24
hypothyroidism
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
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
Causes of Hypothyroidism
• Primary hypothyroidism with Goitre
Aquired
Hashimotos thyroiditis
Iodine deficiency
Drugs blocking synthesis or release of T4
Goitrogens
Cytokines
Thyroid infiltration
Congenital
Iodide transport or utilization defect
Iodotyrosine dehalogenase deficiency
TPO deficiencyn\ nd dysfunction
Defects in thyroglobulin synthesis
27
• 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
following subacute painless or postpartum thyroiditis
28
• 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
• generalised or pituatary dominant
29
30
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
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
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 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
Reproductive
• Arrest of pubertal development• Reduced growth velocity• Menorrhagia, Amenorrhea• Anovulation, InfertilityHepatic
• Increased LDL / TC• Elevated LDL + triglycerides
34
Thyroid Failure - Organ Systems
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
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
• Growthhormone-Decreased D3 activity36
www.drsarma.in
37
Cassava Plant
38
Topiaco - Sago (Javva Arisi)
Tapioca Root - Sago
39
Tapioca (tubers) Dried Tapioca - Sago
Myxedema
40
Myxedema
41
Co-morbidity
• Hypercholosterolemia• Depression• Infertility – Menstrual Irregularities• Diabetes mellitus
42
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
Lipids in Patient with Hypothyroidism
Hypercholesterolemia(>200 mg/dL)
Hypertriglyceridemia(>150 mg/dL)
Hypercholesterolemia and mild Hyper TG
Normal Lipids
44
N= 268
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
Suspect Hypothyroidism
1. Amenorrhea2. Oligomenorrhea3. Menorrhogia4. Galactorrhea5. Premature ovarian failure6. Infertility7. Decreased libido8. Precocious / delayed puberty9. Chronic urticaria 46
47
48
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
Hormone replacement
49
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
• Treatment of choice is levothyroxin
• Not recommended for use :Desiccated thyroid extractCombination of thyroid hormones
T3 replacement except in Myxedema coma
51
Treatment
• 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
Dosage Adjustments
• 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
Start Low and Go Slow
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
• Malabsorption Syndromes
• Reduced AbsorptionCholestyramine resinSucralfateFerrous sulfateSoybean formulaAluminum hydroxideColestipol hydrochloride
55
Drugs that affect metabolismRifampin
Carbamazepine
Phenytoin
Phenobarbitol
Amiodarone
Drug Interactions
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
Inappropriate Dosage
57Massive Pericardial Effusion in Hypo
20.2.98
58Clearing of Pericardial Effusion with Rx.
26.7.98
59Reappearance of Pericardial Effusion after treatment is discontinued
14.9.99
FT4 evaluation
• CENTRAL HYPOTHROIDISM
• AFTER SURGERY
60
Diet in Iodine deficiency
• Iodized salt• Selenium supplementation• Avoid Cassava• Avoid cabbage (goitrogens)• Avoid formula milk• Fish, meat, milk & eggs
61
Special situations
62
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
• TreatmentInitial IV THYROXINE 500-800 mcg/day ,followed by daily dose of
I.V thyroxine 100 mcg thereafter ,alt I.V leothyronine 25mcg b.d63
64
Sick Euthyroid Syndrome
Total T3 reduced FT3 reducedTotal T4 reducedFT4 NormalTSH NormalClinically Euthyroid
Case-1
• 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
65
Case 2
• T3 -1.42nmol/l
• T4-106.96nmol/l
• TSH-<0.05IU/ml
66
67
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
68
top related