Thyroid Function and Disorders
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Wel come
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THYROIDFUNCTIONAND
DISORDERS
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Introduction
Largest endocrine gland
Secrets three hormonesThyroxineTri iodothyronineCalcitonin
Thyroid hormone affect each and every
cells in the body
In India at Sub-Himalayan regions thyroidhormone deficiency leads to mental
retardation and goiter 33
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Anatomy
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Largest endocrine gland
15-25 gm in weight in adult
Bilobed structure joined by isthmus
Located on either side of trachea
Below larynx
Highly vascular structure
Blood flow 400-600ml/100gm/min
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HISTOLOGY
made up of an aggregation of severalfollicles
Functional unit of thyroid gland
Outer rim made up of a single layer offollicular epithelium
Rest on basement membrane
Surrounded by a rich capillary plexus.
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HISTOLOGYClick to edit Master text stylesSecond level
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COLLOID
Homogenous material
Fill in each cavity of follicle
Follicle stimulated- depleted colloidFollicle unstimulated- accumulate colloid
Constitute- thyroglobulin
Glycoprotin MW of 660,000
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PLASMA
T4T3
TISSUE
GUTIODIDE
THYROIDThyroglobulinIodine
T3 & T4
Foodiodine
T4 conjugateT3 sulphate
faeces
urinekidney
plasma
iodine
liver
IODINE CYCLE
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Biosynthesis thyroidhormones
1)Synthesis and secretion of thyroglobulin
2)Iodide trapping3)Oxidation of iodide
4)Organification of thyroglobulin
5)Couplig reaction
6)Storage
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STAGES IN FORMATION OF THYROIDHORMONES
1. IODIDE PUMP( iodide trapping)
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1. OXIDATION OF THE IODIDE ION promoted by enzymeperoxidase
2. IODINATION OF TYROSINEAND FORMATION OF
THYROID HORMONES ORGANIFICATION Iodinaseenzyme
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Monoiodotyrosine and diiodotyrosine 1616
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4. COUPLING
Monoiodotyrosine + diiodotyrosine = T3Diiodotyrosine + diiodotyrosine = T4
Release of T3 and T4 into circulating blood Proteinase enzyme
Transport of T3 and T4 combine with proteins
a.thyroxine binding globulunb.thyroxine binding pre-albuminc.albumin
T4 released to tissues every 6 days and T3 in one day
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storage
Stored in lumen of follicle in combinationwith TG
Each TG molecule contains 30 molecule of
thyroxine and few molecule oftriiodothyronine
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Hormone secretion
Endocytosis-TG retrived from the lumen of follicle byepithelial cell through endocytosis
-Colloid enters in cytoplasm in form ofcolloid droplets
-Moves from cytoplasm to basal
membraneProteolysis-colloid droplets fuses with the lysosomesvesicle-contains proteolytic enzymes 1919
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T4
T3
85% (peripheral conversion)
15%
Protein binding + 0.03% free T4
Protein binding + 0.3% free T3
(10-20x less than T4)
Normal Daily Thyroid Secretion Rate:T4 = 100 ug/dayT3 = 6 ug/day
( ratio T4:T3 = 14:1 )
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DISTRIBUTIONOF THYROID
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Metabolism and excretion ofthyroid hormone
Deiodination
Decarboxilation
Conjugation
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Regulation of thyroidhormone secretion
Hypothalamus-anterior pitutary thyroid axis
Autoregulation of thyroid gland
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1. TSH or Thyrotropin ( from the Anterior Pituitary Gland)
Increases Thyroid Secretion
Effects on the thyroid gland: a. Increased proteolysis of the thyroglobulin
b. Increased activity of the iodide pumpc. Increased iodination of tyrosined. Increased size and increased secretory activity of the
thyroid cellse. Increased number of thyroid cells
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TSH INCREASES ALL KNOWNSECRETORY ACTIVITIESOF THETHYROID GLAND CELLS
Cyclic Adenosine Monophosphate
Mediates the Stimulatory effect of TSH-cAMP act as second messengerin
many target tissues
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Th Th id F lli l
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The Thyroid Follicles
Figure 18.12b2828
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Autoregulation of
thyroid glandRegulated by food iodine contentDeficiency of iodine content in the dietiodine trapping mechanism become super
efficient
Excess of iodine in the food then iodinetrapping become less efficient
Organification of excess of amount ofiodine does not occur
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Wolff-Chaikoff Effect
Increasing doses of I- increasehormone synthesis initially
Higher doses cause cessation
of hormone formation.This effect is countered by theIodide leak from normal thyroidtissue.
Patients with autoimmunethyroiditis may fail to adapt andbecome hypothyroid.
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Jod-Basedow Effect
Opposite of the Wolff-Chaikoff effect
Excessive iodine loads induce hyperthyroidism
Observed in hyperthyroid disease processes
Graves diseaseToxic multinodular goiter
Toxic adenoma
This effect may lead to symptomatic thyrotoxicosis inpatients who receive large iodine doses from
Dietary changes
Contrast administration
Iodine containing medication (Amiodarone)
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MECHANISMS OF THYROID
HORMONE ACTION
Act by binding to Nuclear receptors, termed
Thyroid Hormone Receptors (TRs), Increasing
synthesis of proteins
At mitochondrial level increases number and
activity to increasing ATP production
At Cell membrane increases ions and
substrates transmembrane flux
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Thyroxine and its precursors:
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Thyroxine and its precursors:Activity
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FUNCTIONS OFTHYROID GLAND
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Effects on growth and tissuedevelopment
Body growth and skeletal maturation
- Direct : increases the protein synthesis
and enzymes
- Indirect : increases growth hormone andsomatomedins
Tissue differentiation and maturation
Development of nervous tissue-proper axonal and dendritic development 3535
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Effect on BMR
the basal rate of O2 consumption the heat production in most tissues except.
The brain, retina, gonads, lungs and spleen.
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Effect on metabolism
On carbohydrate metabolism
On fat
On protein
On vitamin metabolism
On water and electrolyte
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Carbohydrate metabolism
Two effects
1)hypoglycemia
Increases
Glucose consumption by peripheral tissues
Glucose uptake by the cells
Insulin secretion
2)hyperglycemia
Increses
Glucose absorption of the GI tract
Glycolysis
Gluconeogenesis
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Fat metabolism
Increase lipolysis and lipid mobilization with:
Cholesterol
Triglycerides
Free fatty acids
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Protein metabolism
Physiologically anabolic-increases protein synthesis
Hyper secretion causes protein catabolism
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Effect on vitaminmetabolism
Increases need for vitamins
- important part of enzymes and
coenzymes
Necessary for conversion of -carotene tovit A
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Respiratory effect
O2 consumption
CO2 and heat production
Rate and depth of respiration
O2 dissociation curve shift to right
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Effect on nervoussystem
cell membrane permeability to Na and K,for the action potential
neurotransmitter synthesis
receptors for neurotransmitters
enzymes that destroy neurotransmitters
Increase speed and amplitude ofperipheral nerve reflexes
Enhances wakefulness and alertness
Enhances memory and learning capacity 4343
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Effect on other endocrineglands
rate of secretion of most of otherendocrine gland
tissue demand for hormones
rate of inactivation of adrenoglucocorticoids so ACTHsecretion increase
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Effect on kidney
blood flow
GFR
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Effects ongastrointestinal tract
Thyroid hormone leads to increases in
- appetite
- food intake
- rate of secretion of digestive juices
- motility of gastrointestinal tract 4646
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Effects Of ThyroidHormones On TheCardiovascular System heart rate
force of cardiac muscle contractions
stroke volume
Cardiac output
U -re ulate catecholamine rece tors 4747
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Effects Of The ThyroidHormones On TheReproductive SystemRequired for normal follicular developmentand ovulation in the female
Required for the normal maintenance of
pregnancy
Required for normal spermatogenesis inthe male
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RELATION WITHCATECHOLAMINECatecholamine and thyroid hormone both- BMR- stimulate CNS
- heart rate and force of contractionCatecholamine can not increases theBMR in absence of thyroid hormone-it potentiates the catecholamine action
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Disorders OF
THYROID GLAND
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When the Thyroid
Doesnt Work
Hyperthyroidism
Too Much Thyroid Hormone
Metabolism Speeds Up
Hypothyroidism
Too Little Thyroid Hormone
Metabolism Slows Down
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Thyroid Evaluation
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Thyroid EvaluationClick to edit Master text stylesSecond level
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?Hyperthyroidism
O S
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HYPERTHYROIDISM
Hyperthyroidism is present when thethyroid gland is over secreting
hormones.
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Causes ofHyperthyroidism
Most common causes
Graves disease
Toxic multinodular goiter
Autonomously functioningnodule
Rarer causes
Thyroiditis or other causes ofdestruction
Thyrotoxicosis factitia
Iodine excess (Jod-Basedowphenomenon)
Struma ovarii
Secondary causes (TSH orHCG)
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HyperthyroidismSymptoms
Hyperactivity/ irritability/ dysphoria
Heat intolerance and sweating
Palpitations
Fatigue and weakness
Weight loss with increase of appetite
Diarrhoea
PolyuriaOligomenorrhoea, loss of libido
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H th idi Si
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Hyperthyroidism Signs
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Tachycardia (AF)
Tremor
Goiter
Warm moist skinProximal muscleweakness
Lid retraction or lag
Gynecomastia
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Complications ofHyperthyroidism
Thyroid Storm or Crisis
Acute aggravation of S & S
Heart failure
Shock
Hyperthermia
Tachycardia, Hypertension
Confusion
Seizures Coma
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Treatment ofhyperthyroidism
A n t i t
B e t a
M E D
S u b t o
S U R
R a d i o
L u g o
I O D
H Y P E
T y p e
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A ti th id d
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Anti thyroid drugs
Chemically block hormone synthesis
Enhance evolution to remission
Best indicated for children,adolescents,young
adults and pregnant women.Propylthiouracil-100-150mg every 6or 8 hrs
Carbimazole- 40-60mg daily initially for 3weeks,then reduce to 20-40mg for another 8
weeks and maintain at 5-20mg daily for 18-24months.
Methimazole-active metabolite of Carbimazole
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Duration of treatment
18-24 months
Side effects- Rash
Leukopenia
Agranulocytosis
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Control of adrenergicsymptomsAdrenergic antagonists:
Propranolol-40-120mg/day
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Surgical Treatment ofHyperthyroidism
Procedure: -thyroidectomysubtotal thyroidectomy
hemithyroidectomy
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Graves Disease
Autoimmune disorder
Abs directed against TSH receptor withintrinsic activity.
Responsible for 60-80% of Thyrotoxicosis
More common in women
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Eye Signs
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N - no signs or symptoms
O only signs (lid retraction or lag)no symptoms
S soft tissue involvement (peri-orbital oedema)
P proptosis (>22 mm)(Hertls test)E extra ocular muscle involvement(diplopia)
C corneal involvement (keratitis)
S sight loss (compression of theoptic nerve)
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Other Manifestations
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Other Manifestations
Pretibial myxoedema
Thyroid acropathy
OnycholysisThyroid enlargement witha bruit frequently audibleover the thyroid
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Diagnosis
TSH , free T4 Thyroid auto antibodies
Nuclear thyroidscintigraphy (I123, Tc99)
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Treatment
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Treatment
Reduce thyroid hormone production or reducethe amount of thyroid tissue
Antithyroid drugs: propyl-thiouracil, carbimazole
RadioiodineSubtotal thyroidectomy relapse after antithyroidtherapy, pregnancy, young people?
Symptomatic treatment
Propranolol
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Hypothyroidism
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Hypothyroidism is present when the thyroidgland is producing little or no thyroidhormones. Thus slowing things down....
Hypothyroidism
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Causes of Hypothyroidism
Autoimmunehypothyroidism(Hashimotos, atrophicthyroiditis)
Iatrogenic(I123treatment,thyroidectomy, externalirradiation of the neck)
Drugs: iodine excess,lithium, antithyroiddrugs, etc
Iodine deficiency Infiltrative disorders of
the thyroid: amyloidosis,sarcoidosis,haemochromatosis, scleroderma
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Symptoms of Hypothyroidism
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Cold intoleranceSlow digestion
Weight gain
FatigueThin, coarse hair
Brittle fingernails
Muscle achesDizziness
Ringing in earsNumbness
Carpal tunnel
Poor memorySkin changes
Voice changes
Milky dischargefrom breasts
Symptoms of Hypothyroidism
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Hypothyroidism Signs
Dry skin, cool extremities
Puffy face, hands and feet
Delayed tendon reflex
relaxation Carpal tunnel syndrome
Bradycardia
Diffuse alopecia
Serous cavity effusions
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How to Rememberthe Signs and Symptoms of
HypothyroidismSleepiness, Fatigue, LethargyLoss of Memory, Trouble Concentrating
Unusually Dry, Coarse Skin
Goiter (Enlarged Thyroid)
Gradual Personality Change, Depression
Increase in Weight, Bloating or Puffiness (Edema)
Sensitivity to Cold
Hair Loss, Sparseness of Hair
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Lab Investigations of
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Lab Investigations ofHypothyroidism
TSH , free T4 Ultrasound of thyroid little value
Thyroid scintigraphy little value
Anti thyroid antibodies anti-TPO
S-CK , s-Chol , s-Triglyseride
Normochromic or macrocytic anemia
ECG: Bradycardia with small QRS complexes
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Myxedema
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Myxedema
Usually appears at the age of 40 yrs
Caused by1) thyroid deficiency due to
-thyroidectomy-neoplasm-chronic thyroiditis-radio-iodine therapy
2)Pitutary deficiency of TSH due to-tumours
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Sign and symptoms
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Sign and symptoms
Skin dry, rough, thick
Facial puffiness
Loss of hair
Husky voice
Intolerance to cold & hypothermia
Bradycardia, low voltage ECGFatigue, extreme somnolence
Poor memory, intellectual deterioration
Consti ation and anorexia 7575
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Treatment
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Treatment
Levothyroxine- altroxine tab given orally
Triiodothyronine for myxedema coma
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CRETINISM
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CRETINISMCaused by extreme hypothyroidism during fetal
life, infancy or childhood.
Characteristics:
a. Failure to growb. Mental retardationc. Skeletal growth characteristically moreinhibited than soft tissue growth
- child is obese, stocky and short appearance-tongue becomes large in relation to
skeletal growth
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CAUSES:
1. Congenital Cretinism results from congenitallack of a thyroid gland failure of thyroid glandto produce thyroid hormone
2.Endemic Cretinism iodine lack in the diet
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Goiter
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Enlargement of the thyroid gland is knownas the goiter-may be associated with the normalthyroid function, hypothyroid andhyperthyroidism.
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Endemic goiter
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Endemic goiter
also known as simple goiterdue to iodine deficiency in diet common
in region like Alps,Himalayan region
Lack of iodineDecreases thyroid homone in blood
Increases TSH secretion
Large amount of colloid formation
Increases size of thyroid
Common in female during puberty,8181
Idiopathic non-toxic
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Idiopathic non-toxiccolloid goiter
- iodine in the diet is normal-TSH secretion is depress which may bedue toa) mild thyroiditis
b) hereditary abnormal enzyme systemwhich are require for TSH synthesis
c) presence of goiterogenic substance indiet
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Hashimotos Thyroiditis
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Hashimoto s Thyroiditis
Common cause of goiter and hypothyroidism
Physical
Painless diffuse goiter
Lab studies
Hypothyroidism
Anti TPO antibodies (90%)
Anti Thyroglobulin antibodies (20-50%)
Acute Hyperthyroidism (5%)
Treatment
Levothyroxine if hypothyroid
Thyroid suppression (levothyroxine) to decrease goiter size
Contraindications
Stop therapy if no resolution noted
Surgery for compression or pain.
Subacute Thyroiditis
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Subacute ThyroiditisDeQuervains, Granulomatous
Most common cause of painfulthyroiditis
Often follows a URI
FNA may reveal multinuleatedgiant cells or granulomatous
change.Course
Pain and thyrotoxicosis (3-6 weeks)
Asymptomatic euthyroidism
Hypothyroid period (weeks to months)
Recovery (complete in 95% after 4-6months)
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Acute Thyroiditis
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Acute Thyroiditis
Causes68% Bacterial (S. aureus, S. pyogenes)
15% Fungal
9% Mycobacterial
May occur secondary to
Pyriform sinus fistulae
Pharyngeal space infections
Persistent Thyroglossal remnants
Thyroid surgery wound infections (rare)
More common in HIV
Acute Thyroiditis
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Acute Thyroiditis
DiagnosisWarm, tender, enlarged thyroid
FNA to drain abscess, obtain culture
RAIU normal (versus decreased in DeQuervains)
CT or US if infected TGDC suspected
Treatment
High mortality without prompt treatment
IV Antibiotics
Nafcillin / Gentamycin or Rocephin for empiric therapy
Search for pyriform fistulae (BA swallow, endoscopy)
Recovery is usually complete
Riedels Thyroiditis
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Riedel s Thyroiditis
Rare disease involving fibrosis of the thyroid gland
Diagnosis
Thyroid antibodies are present in 2/3
Painless goiter woodyOpen biopsy often needed to diagnose
Associated with focal sclerosis syndromes (retroperitoneal, mediastinal,retroorbital, and sclerosing cholangitis)
TreatmentResection for compressive symptoms
Chemotherapy with Tamoxifen, Methotrexate, or steroids may be effective
Thyroid hormone only for symptoms of hypothyroidism
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Thankyou