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Thyroid

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jay acharya

on 8 November 2012

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Transcript of Thyroid

Clinical menifestation of thyrotoxicosis Thyroiditis -acute onset of symtoms
Masked symtoms in elderly
CVS-Tachycardia, widened pulse pressure
up to 20% will have AF, may present as heart failure
60% revert to sinus rhythem after treatnent within 4 months
Mitral valve prolapse is more common than general population
Protien,Fat and Carbohydrate-Muscle wasting and proximal muscle wasting
Lipolysis with increse FFA

Nervous System-Sympathetic-Epinephrine and NorEpinepherine levels are not raised
but thyroid harmone increse sensitivity of catecholamine
cardiomyocytes and adipocytes
Nervousness,hyperkinesia emotional lability,tremor
Muscle-Proximal myopathy, more in men
1% graves discease devolopes myasthenia gravis
Graves disease occures in 3-5% patients wirh myasthenia Skeletal system-h due to bone resorption,hypercalcemia, Increase ALP

HHaematopoetic-3% patients will have pernicious anemia
low WBC due to low neutrophils
Require low dose of warfarin
RS- dysnoea
Eyes-Lid retraction, Lid lag-incresed adrenergic activity
Skin &Hair-sweating,palmar erythema, telengetasia,, excessive hair loss,Plummers nail.
Pituitary&adrenocortical function- Sub normal response to ITT
Normal cortisol levels
Reproduction-Increase Libido,menustrual irregularities
Gynecomastia, errectile dysfunction in males-incresed conversion of androgens to
estrogens Graves Auto antibodies against -TPO,thyroglobulin,TSHR
TSHRab specific to graves
Level decrease with treatment
in treated Graves -TSHR-blocking Ab may appear
Graves-nonhomogenous lymphcytic infiltration
Lack of supressor CD8+ cells
Risk factors for graves-Genetic-Hashimatos,DMtype1,perncious anemia
Stress-Some evidence appear after stressfull event
Common in females and after puberty
Men -tends to occur at later age
Pregnancy-uncommon during pregnancy-due to immune suppression
30% young women with Graves-history of pregnancy in last 12 months
Drugs-Iodine , Iodine contining drugss Pathophysiology Undetectable TSH
Increased Iodine clearance, increased blood flow, Increase in T3 -due to
secretion and also peripheral conversion Clinical features General-


Eyes-Lidlag lid retraction( sympathetic)
Infiltrative opthalmopathy- follows independent course from thyrotoxicosis
occasionally occur in euthyroid patients
Exopthalmus-Hertel or Luedde exopthalmometer-upper limit os 20 mm
upward gaze may be limited
severe forms includes infections,optic nerve ischemia, papilloedema
American Thyroid association classification- NOSPECS
0- No signs and symtoms
1- Only signs( proptosis up to 22 mm, lid retraction stare)
2-Soft tissue involvement
3-Proptosis>22 mm
4-Extraocular muscle involvement
5-Corneal involement
6-Sight loss
Treatment-Mild- eye protection and symtomatic treatment
Severe-Steroids, External radiation, Orbital decompression
Infiltrative dermopathy- up to 10% patients
clubbing, pretibial myxedema Treatment -symtomatic Management Lab-Suppressed TSH
Elevated T4 & T3, T3 proportionatly more than T4
But severe accompanying illeness, T3 may be normal (lack of p.conversion)
RAIU -not usefull in clinicaly strightforward Graves
but low RAIU factious hyperthyroid,ectopic thyroid tissue,viral thyroiditis,
TSHRab-2 bio-assays available
1 capacity of patient serum or Ig G to inhibit binding of radiolabelled TSH to receptors
Low cost, Sensitivity >90%
2 capacity of patient serum to stimulate adenylate cyclase in thyroid epithelial cells
Expensive, sensitivity 80-90%
Indications: Euthyroid exopthalmos,TSHRab titres in pregnancy(to assess risk of feotal thyrotoxicosis) Thionamides inhibit Oxidation and binding of thyroid iodide
- intrathyroidal iodine deficiency
-increse T3/T4 ratio- In addition large doses of PTU also inhibit
conversion of T4 to T3 by type 1 deiodinase
enzyme in the peripheral tissues Thionamides also has immuno suppressive action Theurepetic response may take up
to 2-6weeks(gland harmone storage) Treatment Block and replacement To contiue using thionamides -to attenuate natural history of auimmune thyroid disease
Fewer blood monitoring and dose adjustments Graves in pregnancy low rate in pregnancy due suppressed auto immune process
Both accompanied by thyroid stimulation,hyperdynamic circulationa and hypermetabolic state
Increse T4 and T3 suppressed TSH (modest0.1 to 0.4)
Dose of antithyroid drug will reduce in pregnancy-give smallest dose (PTU<200)

Management- Block and Replace not appropriate,Possibility of foetal hypothyroidism and teratogenesity(aplasia cutis) considered,Aim Free T4 upper range for normal, PTU-less teratogenic
Intense foetal monitoring required
Surgery- may be considered in 2 nd trimester Adverse effects-Mild-skin rash arthralgia,sialadenitis,GI symtoms
Severe-Agranulocytosis <1% first few weeks or months
Rx-withdrawal, Antibiotics,granulocyte colony stimulating factor
others-myalgia,neuritis,hepatits cholestasis,SLE like syndrome,toxic psycosis Treatment Iodine and Iodine containing agents-Inhibit harmone release by incresing glandular storge of iodine
So used in preparation for surgery and thyrotoxic crisis
cautions- Effects reversible on withdrawl of iodine,Also reduces the benefit of Thionamides or RAI
Some times effects may be partial or nil, and effect may wear off with time
Other Agents
Lithium-tempory control for patients allergic to thionamides and iodine
Dexamethasone- 8mg/day can be used as additive agent peripheral conversion T4 to T3
B-Blockers
Surgery-Subtotal bilateral thyroidectomy
Complication-Recurrent hyperthyroidism 2%,vocal cord palsy 2.5%(mostly transient) Hypocalcemia
3.7%, hypothyroidism
Radio Iodine- no increse in carcinogenesity,
Late hypothyroidism,radiation thyroididtis-10-14 days after present with thyrotoxic crisis
Worsening of orbitopathy-10% of graves eye disease-prednisolone 0.5 mg/kg 4/52 before & up to 3/12 Non immune hyperthyrodism Toxic multinodular Goitre-autosomal dominant, common in females
funtional autonomy of multi nodular goitre
clinically mild hyperthyroidism
common after 50 yr inpatients with goitre
No eye disease
Management-TSH between 0.1-0.4 mU/L
RadioIodine treatment of choice Toxic adenoma Presents as nodule with suppressed TSH
Age group 30-40 yrs
RAI uptake scan
Treatment -RadioIodine
Surgery Amiodarone induced thyrotoxicosis Common drug causing thyrotoxicosis
resembles T4
37% iodine by weight, 75 mg in 200 mg of tablet(daily req 200 mcg)
Also inhits de-iodinise enzymes
Amiodarone also has direct cytotoxic effect on thyroid cells
Thyrotoxicosis type 1-Doppler flow ultrasonography, incresed gland,vascularity
discontinue if possible

Throtoxicosis type 2-thyroiditis type
Doppler flow ultrasonography-normal gland,vascularity
discontinue
Carbimazole, and prednisole 20-40 mg/day

Patients amiodarone can't be withdrawn- Thionamides ,but thyroidectomy
is the treatment of choice Hyperthyroidism due to thyrotropin Rare
Incresed TSH and diffuse goitre and thyrotoxic symtoms Hyperthyroidism-Thyroid harmone resistence Mutation in thyroid harmone receptor in Hypothalamo-pitutary feedback
receptor which is beta iso form Transient Gestational thyrotoxicosis Transient thyrotoxicosis Abrupt onset and shorter duration
1.Auto immune- Hashimotos thyroditis
Common is painless form -mild
Painfull form -more acute onset
Positive TPO,Ultrasound-inflamed gland
No eye or dermopathy
thyrotoxic phase last for 1-2 months
Prednisolone reduce duration of toxic phase
1/2 become hypothyroid
2.Post Viral-sub acute thyroditis-painfull
apoptosis of folicular epithelium
release of thyroglobulin and T4 to circulation
Decresed TSH
High ESR
Aspirin , NSAID and steroids
3.Bacterial/Fungal infections

4. Drug associated-Amiodarone
Interleukin-2,interferon Alfa, GM-CSF,sunitibe age at: lpi.oregonstate.edu/.../iodine/thyroid.htm
The overwhelming majority (99%) of circulating thyroid hormones are bound to serum proteins, mostly thyroid-binding globulin (TBG). The small percentage of free thyroid hormones, those not bound to TBG, act as the active form T4 T3 Thyroid storm Extreme thyrotoxicosis
Uncommon but serious complication in association with Graves, Toxic multinodular goitre,
poorly prepared subtotal thyroidectomy
precipitated by infection trauma or surgery,DKA,radiation thyroiditis,toxemia of pregnancy
CF: severe hypermetabolism
Rx
PTU 300 mg x4h by mouth
Iodine (SSKI-saturated solution of potassium Iodide- 5 drops -6hourly)
Dexamethasone 2mg 6 hourly

Supportive treatment Hypothyroidism Skin- cumulation of hyaluronic acid -myxedema apparence
dry skin,dealy healinghypercarotenemia,
hair loss-eyebrows CVS reduced ardiac output
pericardial effusion
angina pectoris,heart blocks RS- Pleural effusion GI Fluid retension
associated with pernicious anemia and gluten intolerence CNS reduced intellectual function mistaken for dementia in elderly
thick slurred speech, nerve compression
delayed tendon jerks Others decresed libido, anovulation
low body temeperature
anemia
high LDL and triglycerides Lab reduced Thyroid harmones(exept in thyroid resistence)
Raised TSH (exept in secondary) Hashimotos thyroiditis-autoimmune common, prevelence 3.5 per 1000 in women
Autoantibodies to TPO, Tg and TSH

Pathology-apoptotic distruction of thyroid cells
lymphocytic infitration -microscopy
Risk factors-
Genetic-HLA-DR5
downs syndrome
Pregnancy-postpartum thyroiditis
Iodine and iodine containing drugs
Irradiation
Infection-viral Differential diagnosis Thyroid carcinoma, Nephrotic syndrome Treatment Thyroxine replacement-
Levothyroxine -7 day half life
typical dose-1.6-1.8microgrms/wt Kg
Primary hypothyroidism-aim to return TSH normal
Lower doses in elderly patients with IHD
25-50% increase dose in pregnancy and reduced to pre-pregnancy
level at the time of delivery
Effects-diuresis
improve apetite, pycomotor activity hoarsness

Surgery -pressure symptoms Other causes(goitre) Endemic(iodine deificiency)
Iodine excess-chronic excess iodine administration
Drugs(Block thyroxine synthesis)-Lithium,PAS,ethionamide
Goitrogens in foods-cabbages, turnips and many used animal fodder
cytokines-IL2, interferon alpha
Pendreds syndrome Non Goitrous Post ablative
Thyroid agenesis
Central hypothyroidism
Resistence to thyroid harmone Incresed thyroxine requirement Pregnancy
GI dosrders
Drugs-chylostyramine, sucralfateferrous sulphate
Increse cytochrome p450-rifampicin, carbamazepine,estrogen,phenytoin, ? statins
Amiodarone-block T4 to T3 conversion
Selenium blocks deiodinase synthesis Myxedema coma Eldery patients, winter months
Hypothermia. bradycardia, alveolar hypoventilation-co2 retension,hyponatremia
precipitaing factroes- CNS depresants, infection,trauma
Levothyroxine 500 mcg IV or 25 mcg -12 hourly
Hydrocortisone
correction of electrolyte duistrubances, IV fluids, assisted ventilation, rewarming image at: www.jcrows.com/hypothyroidism.html Clinical menifestation of thyrotoxicosis Factors altering binding of T4
to TBG
Increase Binding:
• Estrogens & Estrogen Receptors Modulators
• Methadone
• Clofibrate
• 5-FU
• Tamoxifen
• Liver disease
• HIV infection
• Porphyria
• Inheritance ‰Decrease Binding:-
• Glucocorticoids
• Androgen
• L-Asparaginase
• Salicylates
• Mefenamic acid
• Phenytoin
• Carbamazepine
• Frusemide
• Acute and chronic illness Recommended daily iodine intake in
humans (WHO/UNICEF)
Age group Iodine requirement(g)
• Infants (0 -11mth) 50
• Children (12 mth - 59 mth) 90
• School age child (6-12 year) 120
• Adults (above 12 year) 150
• Pregnant & lactating women 200 Thyroid Hormones -
Degradation
• T4 –show elimination t1/2 6 to 8 days
• Hyperthyroidism t1/2 shortened 3 - 4 days
• During ↑ TBG binding, clearance ↓
• T3 t1/2 is 1day
• T4 & T3 conjugation in liver and entero-hepatic
circulation External scintiscaning
Either Technetium or Iodine Ultrasound as small as 2-3 mm detected

CT scan/MRI Presence and extend of retrosternal goitre PET Scaning Radiolabelled Fludrodeoxy Glucose(FDG)
Used in Papilary/follicular caarcinoma with no RadioIodine uptake
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