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1.LIVER FUNCTION TESTS1.LIVER FUNCTION TESTS
2.RENAL FUNCTIONS TESTS2.RENAL FUNCTIONS TESTS
3.THYROID FUNCTION TESTS3.THYROID FUNCTION TESTS
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Entero hepatic Circulation
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Portal Hypertension
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Jaundice
Bilirubin > 2mg/dl
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Usually accompanied by jaundice & pruritis
Due to primary liver disease drug interference with bile secretion pregnancy
Elevated blood cholesterol Xanthomas Increased ALKP
Cholestasis
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Anatomic Types of Cirrhosis Portal
caused by diffuse liver cell injury
repeated episodes of necrosis followed by regeneration & growth of fibrous tissue from portal triad area
most common type usually due to alcoholic liver
disease or chronic viral hepatits
Biliary caused by chronic disease
of the biliary tree chronic inflammation of bile
ducts due to autoimmune disease obstruction by gallstones sclerosing cholangitis
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Cirrhosis
Final, common end-stage for a variety of chronic liver diseases
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Final & irreversible stage of alcoholic liver disease
Only about 15% of alcoholics develop
One of the leading causes of liver transplantation
Alcoholic Cirrhosis
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Hepatitis B HBV Infects hundreds of millions worldwide Incubation varies from a few weeks to 6 months
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Hepatitis C Major cause of chronic liver disease Incubation varies from a few weeks to 6
months About 40,000 new cases/ yr
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Autosomal recessive disorder Toxic accumulation of copper mainly in brain & liver Copper absorbed in GI tract & excreted in bile
albumin transports to liver bound to ceruloplasmin then secreted if biliary excretion decreases, accumulates in liver & brain
Manifests as behavioral oddities, psychosis, tremors, abnormal gait
Diagnosis confirmed by liver biopsy Early diagnosis critical Chelation therapy
Wilson Disease
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Primary Biliary Cirrhosis Autoimmune disease Usually have another
autoimmune disease Evolves from
inflammatory destruction of intrahepatic bile ducts
Early on see accumulation of lymphocytes around bile ducts
Death due to hepatic failure & portal HTN
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Obstruction of the Extrahepatic Bile Ducts
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Gallstones in the gallbladder or biliary tree
Form in gallbladder Usually have multiple stones About 1 million new cases/yr
50% require surgery
Cholelithiasis
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Cholesterol gallstones 80% of cases Bile saturated with
cholesterol Conditions associated
with their development age & gender weight ethnic, hereditary, &
geographic factors drugs acquired conditions
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Pigment gallstones 20% of cases Form in gallbladder & in biliary tree Composed of bilirubin & bile substances
other than cholesterol23
Acute Cholecystitis Most common
major complication of gallstones 90% associated
with obstruction of the neck
Gallbladder is enlarged, tense, & inflamed
Persistent rather mild RUQ pain to very severe pain
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Chronic Cholecystitis Do not have to
have a history of acute attacks
Almost always associated with gallstones ,
Mild to moderate RUQ pain
Nausea/vomiting Intolerance of
fatty foods25
Die within a few weeks or months May be sudden injury or chronic injury Loss of 90% of function Clinically
jaundice ascites fetor hepaticas hypoalbuminemia hypoglycemia palmar erythema spider angiomata testicular atrophy balding gynecomastia bleeding disorders hepatorenal syndrome hepatic encephalopathy
Hepatic Failure
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Hepatocellular Carcinoma
Usually related to HBV & HCV Hematogenous metastases are common High levels of alpha fetoprotein Prognosis is grim 27
Metastatic Carcinoma
Most common neoplasm in the liver Usually from colon, lung, breast
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Fulminant Hepatic Failure Acute liver disease that progresses to hepatic failure
or encephalopathy in just a few weeks More than ½ of the cases are fulminant hepatitis
usually involving HAV or HBV Other causes include drugs, heat stroke
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Liver is largest organ of the body Weight:
1–1.5 kg(1.5–2.5% of the lean body mass) Located in the right upper quadrant of abd
Under the right lower rib cage. Dual blood supply
~20% oxygen rich blood from the hepatic artery
80% is nutrient rich blood from the portal vein.
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Two lobes: Right & Left Anatomical division
By line joining gall bladder fossa to IVC Histology:
Hepatocytes Kupffer cells Ito cell Cannalicular cells.
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Synthesis of serum proteins Albumin, Carrier proteins
Coagulation factors synthesis Production of bile and its carriers
Bile acids, Cholesterol, Phospholipids Regulation of nutrients
Glucose, Glycogen Metabolism & conjugation
Lipophilic compounds (Bilirubin, Drugs) For excretion in the bile or urine.
Functions of Liver
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Serum Bilirubin (Conjugation) Urine Bilirubin (Conjugation) Blood Ammonia Serum enzymes reflect hepatocytes damage:
ASpartate amino- Transferase (AST) (SGOT) Alanine amino- Transferase (ALT) (SGPT)
Serum enzymes reflecting cholestasis: Alkaline phosphatase (AP) 5′- nucleotidase Gamma glutamyl trans peptidase (GGT)
Detoxification or excretory functions
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Context of the patient’s risk factors Symptoms Concomitant conditions Medications Physical findings It rarely provide specific Diagnosis
Suggest general category of liver disease Different Labs give different N values
Functions of Liver Interpretation of results
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Bilirubin is a breakdown product Porphyrin ring of heme -containing proteins
With van den Bergh method Unconjugated (indirect)
0.7mg/dl Insoluble in water & bound to albumin in blood
Conjugated (direct) 0.3 mg/dl Water soluble & excreted by kidney
With Newer test methods 100% serum Bilirubin = Unconjugated !!
Normal total serum Bilirubin = 1.2-1.4 mg/dl
Serum bilirubin
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Increased Production Hemolytic Disorders (not > 5 mg/dl)
Spherocytosis, G6PD Def, Sickle Anaenia (inherited)
PNH (Paroxysmal Nocturnal Haemaglobinuria) Immune Hemolysis, Microangiopathic Haemolysis
Ineffective Erythropoiesis Cobalamin, Folate, Thalassemia, Severe Iron def
Drugs (Rifampicin, Probenecid, Ribavirin) Resolving large haematoma
Defective uptake / conjugation (Inherited) Crigler Najjar (Type I - II) Gilbert’s Syndrome
Indirect hyper- bilirubinaemia
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Direct Bilirubin > 50% of total Bilirubin in Obstruction / Parenchymal disease Rarely > 30 mg/dl Filtered at the glomerulus
Majority reabsorbed by the proximal tubules Small fraction appears in Urine
All conjugated
Direct hyper- bilirubinaemia
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Direct hyper- bilirubinaemia
Bile duct obstruction
Hepatitis Cirrhosis All
Primary biliary cirrhosis
Medications / Toxins
Primary Sclerosing Cholangitis
Sepsis
Intrahepatic Cholestasis of Pregnancy
Benign recurrent Cholestasis
Dubin-Johnson syndrome
Rotor syndrome
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Unconjugated Bilirubin Always binds to albumin in the serum Not filtered by kidney
Only Conjugated Bilirubin found in urine Implies presence of Liver disease OR Outflow obstruction
Detected by urine dipstick test
Urine bilirubin
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Family of isoenzyme For hydrolysis of many P esters at alkaline pH Require Zn for activity
Present in all tissues Liver, Bone, Gut, Placenta, Kidney
Initial evaluation determine hepatic or nonhepatic origin Concomitant rise of other serum Enzymes Levels NOT reliable indicators
Of severity of liver disease OR To distinguish intra / extra hepatic disease
Alkaline phosphatase
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ALP > 1000 (normal 33-96 u/l) Malignant Biliary obstruction Sepsis AIDS with systemic infection
Decrease : Hypothyroidism Pernicious anemia, Zn deficiency Wilson’s disease Severe hepatic insufficiency
Alkaline phosphatase
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Major plasma protein Responsible for osmotic pressure of plasma
Synthesized by Liver Half life 20 days Normal value 3.5 to 5.5 gm/dl Decreased in
Chronic liver disease Other Causes
Malnutrition Nephrotic Syndrome Protein Losing Enteropathy
Serum albumin
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Hypoalbuminemia
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Produced by stimulated B lymphocyte Serum Globulin elevation in
Chronic Liver Disease Chronic Inflammation and Malignant Disease
Normal value 1.5 – 3.5 gm/dl Normal Albumin & Globulin Ratio 2 – 2.5 : 1
Reversal seen in Chronic Liver Disease (Cirrhosis) Late Feature
Serum Globulin
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Reflect damage to hepatocytes (Necrosis) ASpartate amino-Transferase (AST) (SGOT)
Alanine amino- Transferase (ALT) (SGPT)
Located inside hepatocytesReleased after hepatocyte damageNot specific to liver
Found in many body tissuesElevation > 3 X normal is significant
Serum enzymes: liver damage
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Serum enzymes that reflect cholestasis / Obstruction : Alkaline phosphatase (AP) 5′-nucleotidase Gamma Glutamyl Transpeptidase
(GGT) Located near bile cannaliculi Released after obstruction and
Cannalicular damage
Serum enzymescholestasis / obstruction
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< 1 : Majority of liver disease>2
Extra hepatic sourceAlcoholic Hepatitis Ischemic and Toxin Acute Wilson’s disease : hemolysis
Cirrhosis>4 : fulminant Wilson’s disease
Ast /alt ratio
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Acute viral hepatitis (A-E, herpes)Medications / toxins Ischemic hepatitisHeat strokeAutoimmune hepatitisAcute Budd- Chiari syndrome Wilson’s diseaseAcute bile duct obstruction (rare) Hepatic artery ligation
>75 times = Ischemic & Toxic hepatitisAST> ALT = Ischemic & Toxic hepatitis
Alt & ast > 15 times
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Catalyzes transfer of - glutamyl groups of peptides to other amino acid
Abundant in liver, kidney, pancreas, intestine, and prostate, spleen, heart, brain But not in bone
T1/2 7-10 days28 days in alcohol-associated liver injury
Gamma glutamyl transferase (GGT)
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Increased inAlcohol Drug
Anticonvulsant (CBZ, phenytoin, and barbiturate), warfarin, Oral Contraceptives
Almost all type of liver diseases COPD, Renal failure, DM, Hyperthyroidism, RA, AMI, Pancreatic disease
Gamma glutamyl transferase (GGT)
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Non specificRhabdomyolysisMyocardial InfarctionHaemolysis, Cerebral StrokeAcute or Chronic liver disease
Useful in ,Ischemic hepatitisTransient, massive elevation
Malignant infiltration of liverSustained elevation with ALP
LDH
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During protein metabolism Produced in body by intestinal bacteria
Liver detoxifies Ammonia By converting to urea (excreted by kidneys)
Blood ammonia level Detecting EncephalopathyFor monitoring Hepatic synthetic function (Urea)
Very poor correlation with, Severity of acute encephalopathy
Blood ammonia
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Initial approach
History Symptoms Risk factors for
Liver disease Concomitant
conditions Medications Occupational
exposure to hepatotoxins
Physical Exam Splenomegaly
Ascites Cutaneous stigmata of chronic liver disease
History & physical examinationAlgorithm approach useful when no clinical clues
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Alpha-fetoprotein Ultrasound Ultrsound guided FNAC liverbiopsy
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Several tests for diagnosis Immunological tests Enzymes tests Biopsy- hepatomegaly,
splenomegaly jaundice cirrhosis, hepatitis.
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Based on Kidney Function & Clinical Utility
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Classification – Kidney Function Test
Group I Overall functioning of kidneys
Complete urine analysisMeasurement of non-protein nitrogenous substances in bloodMeasurement of serum electrolytes
Group II
Markers of glomerular filtration rate
Clearance tests
Group III
Markers of glomerular permeability
Microalbuminuria Proteinuria
Group IV
Markers of tubular dysfunction
Osmolality – plasma & urineConcentration and dilution testsTests to assess renal acidification
Test for glomerular filtration rate (GFR)
Useful index for the assessment of severity of kidney damage
Definition: ‘Clearance is defined as the quantity of blood or plasma that is completely cleared of a substance per unit time’
Units: ml/min
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Clearance tests
Creatinine clearance:
- Otto Folin: estimated it in 1904- formation of creatinine is continuous, spontaneous and non-enzymatic- dependent on muscle mass of the body- Reference range: 85 to 125 ml/min
Inulin clearance:- polysaccharide of fructose- neither absorbed nor secreted by tubules- Reference value: 125ml/min
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Clearance tests
Volume
Polyuria: Urine output > 2.5 litres/day
Oliguria: Urine outout 300 to 500 ml/day
Anuria: Urine output < 50 ml/day61
Urine Analysis – Physical Characteristics
Normal Range Conditions increased
Conditions decreased
1000 – 1800 ml/day
Diuretic therapyDiabetes insipidusDiabetes mellitus
Excess sweatingDehydrationAcute renal failure
Appearance: Clear and transparent Turbid Excess phosphates, Urinary tract infection Odour: Aromatic Smell of acetone: Diabetic ketoacidosis Fishy: Presence of bloodColour: Amber-yellow High colour Jaundice Red colour Blood pH: 6.0 (Range: 5.5 to 7.5)
Metabolic acidosis, Metabolic alkalosis
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Urine Analysis – Physical Characteristics
Specific gravity Instrument: ‘ Urinometer’
Fixed specific gravity of 1.010: Chronic renal failure
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Urine Analysis – Physical Characteristics
Normal Range Conditions increased
Conditions decreased
1.016 to 1.022 Diabetes mellitusNephrosisExcessive sweating
Excess water intakeChronic nephritisDiabetes insipidus
Abnormal Constituent
Name of the Test
Associated Clinical Conditions
Characteristics
Reducing Sugar or substance
Benedict’s test
Diabetes mellitusGestational DiabetesRenal glycosuriaEssential PentosuriaGalactosemiaHereditary fructose intoleranceEssential fructosuriaLactosuriaHomogentisicaciduria
Ketone bodies
Rothera’s testGerhad’s test
Diabetic ketoacidosisStarvation ketoacidosisVon Gierke’s disease
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Urine analysis – Chemical Characteristics
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Urine analysis – Chemical CharacteristicsAbnormal
Constituent
Name of the Test
Associated Clinical Conditions
Characteristics
Proteins Heat & Acetic acid testSulphosalicylic acid testHeller’s test
GlomerulonephritisPyelonephritisNephrotic syndrome
Blood Benzidine test
Stones in ureterGlomerulonephritisRenal tuberculosisTrauma to genito-urinary tractCarcinoma urinary bladderUrinary tract infection
Abnormal Constituent
Name of the Test
Associated Clinical Conditions
Characteristics
Bile salts Hay’s test
Viral hepatitisAlcoholic hepatitis Toxic hepatitisDrug induced hepatitisObstructive jaundice
Bile pigments
Fouchet’s test
Urine analysis – Chemical Characteristics
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Major route of excretion Urine levels is seen in kidney dysfunction Blood Urea: (normal 20-40 gm%/dl) End product of protein metabolism Serum Uric acid: (normal ) End product of purine metabolism Serum Creatinine ( normal 0.6 to 1.2
mg/dl) Anhydride form of c reatine formed in
muscles
NPN Substances measurement
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Segment of Nephron Substance reabsorbed
Substance secreted
Proximal Convoluted Tubule (PCT)
SodiumChlorideBicarbonateWater (Obligatory)
H+
Organic acids and basesNH4
+
Loop of Henle SodiumChlorideCalciumMagnesium
---
Distal Convoluted Tubule (DCT)
SodiumChlorideWater (Facultative)
H+
K+
NH4+
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Serum Electrolytes
Reabsorption and secretion of electrolytes is essential for the maintenance of body’s acid-base balance
Microalbuminuria Syn: Minimal albuminuria/ pauci-
albuminuria Small quantity of albumin in urine 30 to 300 mg/day Cause: abnormally high permeability for
albumin in the renal glomerulus Use: early marker for nephropathy in
patients with diabetes and hypertensiom
Markers of Glomerular Permeability
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Specific gravity Instrument: ‘Urinometer’ earliest manifestation of renal disease
difficulty in concentrating the urine alterations in specific gravity
Renal biopsy :
Tests for renal tubular function
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Chronic renal failure with normal sized kidney
Unexplained acute renal failureNephrotic syndrome in children'sGlomerular proteinuria in adultsIsolated haematuria/ proteinuria.
Renal biopsy
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Kidney Function Test - SummaryMeasurement of GFR Clearance tests
Endogenous substance used for clearance tests
Creatinine
Exogenous substance used for clearance testes
Inulin
Volume, Appearance, Colour, Odour, Specific gravity
Physical Characteristics
Measurement of specific gravity Urinometer
Reducing substance, Ketone bodies, Proteins, Blood, Bile salts and Bile pigments
Abnormal chemical constituents
Early detection of Diabetic and hypertensive nephropathy
Microalbumine
Specific gravity, Concentration test, Urine volume, Osmolality, Dilution test, Acidification
Renal tubular function
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SCREENING FOR THYROID DYSFUNCTION
SURVILENCE
MONITERING.
INTRODUCTION
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Neonates for congenital hypothyroidism
Patients With Autoimmune Disease.
Strong family history of family disease
Patients with suspected hyperthyroidism/hypothyroidism
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Postpartum thyroiditisPost neck irradiationPost destructive treatment for thyrotoxicosis
Monitoring treatment for hyperthyroidism with antithyroid drugs
Patients with primary hypothyroidism77
Based on Thyroid Function & Clinical Utility
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Classification – Thyroid Function Test
Group I Primary function of thyroid
Radio-iodine uptake T3 – suppression testTSH – stimulation testTRH stimulation test
Group II Measurement of blood levels of thyroid hormones
Total T3 and T4 levelsFree T3 and Free T4 levelsCirculating TSH levelPlasma tyrosine level
Group III
Metabolic effects of Thyroid hormones
Basal Metabolic RateSerum cholesterol levelSerum creatine levelSerum uric acid levelSerum creatine kinase level
Group IV
Immunological tests for auto-immune disorders
Agar gel diffusion testComplement fixation test
Radioactive ‘Uptake’ studies I131 ‘tracer’ used for thyroid studies Normal: 20 to 40% TSH – stimulation test Basal levels of thyroid hormones is
measured 3 injections of TSH each of 5 USP units is
given 8 hourly Failure to produce thyroid hormones
Primary hypothyroidism Stimulation of gland by production of
thyroid hormones secondary hypothyroidism
Tests based on primary function of thyroid
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Hormone Method Reference Range
Total T4 ELISAChemiluminescenceRadioimmunoassay
5 to 12 g/dl
Total T3 120 to 190 ng/dl
TSH 0.5 to 4.5 mIU/ml
Free T3 Chemiluminescence
0.2 to 0.5 ng/dl
Free T4 0.7 to 1.8 ng/dl
Plasma Tyrosine
60 to 70 Mol/L
MEASUREMENT OF BLOOD LEVELS OF THYROID HORMONES
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Disorder Causes Thyroid profile
Levels
Primary Hypothyroidism
CongenitalRadiation damageSurgical removalViral infectionAuto-immune
T3T4
TSH
Secondary Hypothyroidism
Damage to the pituitary gland
T3T4
TSH
Hyperthyroidism
Graves diseaseToxic adenomaMulti-nodular goitreThyroid hormone overdose
T3T4
TSH
Clinical Application of Thyroid Hormone Measurement
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Thyroid Function Test - Summary
Primary function of thyroid assessment
Radioactive iodine – I131
Decrease in T3, Decrease in T4 & Increase in TSH
Primary hypothyroidism
Increase in T3, Increase in T4 & Decrease in TSH
Hyperthyroidism
Anti-thyroid antibodies
Hashimoto’s Thyroiditis
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Thyroid nodule
History& physical examination
TSHLow TSH
High or
normal
scintigraphy
coldhot
Perform
FNACbenign
U/S guided FNAC
Benign- ve
Malignant +ve
Suspicious
Inadequate
Repeat FNAC
Surgery Surgery Observe
and repeat FNAC 1 year
Or levothroxin
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