@Grv Jaundice on Graves Pkb-dr.iza

download @Grv Jaundice on Graves Pkb-dr.iza

of 44

Transcript of @Grv Jaundice on Graves Pkb-dr.iza

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    1/44

    Jaundice in a Patient withGraves Disease

    Musofa Rusli

    Gatot Soegiarto

    Agung Pranoto

    Internal Medic ine Dept.

    Air langg a Med. Schoo l/ Dr. Soetomo Hosp ital Surabaya

    2006

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    2/44

    Introduction

    Graves disease (GD)Autoimmune disease : binding of TsAb

    thyroid increased thyroid hormonesecretion hyperthyroidism

    Jaundice in GD patient : Concomitant hepatitic viral infection

    Hyperthyroidism

    Thyroid heart disease (pump failure)

    Drug cytotoxicity

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    3/44

    Case

    Mrs. R, female, 31 yo,

    Maduranese

    Admission: April 28, 2005

    (referral from KarangTembok Hospital Sby)

    Chief complaint: yellowish

    color on both eyes for 5 d.

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    4/44

    Initial Examination

    Jaundice since 5 days prior toadmission, getting worse, dark-coloured urine (+)

    Abdominal bloating since 5 daysprior to admission; with nausea,and anorexia

    Weight loss, irregular menstrualperiod, frequent defecation, nopruritus

    Lethargy, dyspnea on exertion,edema of the lower limbs (+)

    Goiter and palpitation since 6months, and since then receivedantithyroid medication

    Conscious, weak, pallor, icteric

    BP 110/60, pulse 108, RR 28,

    temp 37.3

    Exophtalmos +, JVP, goiter:

    diffuse, tender Ictus cordis: 2 cm lat left MCL,

    liver: enlarged 2 cm bac, tender,

    sharp edged

    Mild tremoron ext, lower limb

    mild edema

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    5/44

    Laboratory - Imaging

    Hb 10.6, leuko 4800,

    thrombo 126000, PCV

    0.29, CPG 96, BUN 7,

    SC 0.2, K 2.4, Na 137.

    UA: bilirubin (+2), keton(-), SG 1,010.

    Bilirubin: direct 18.87,

    total 25.29; SGOT 148,

    SGPT 93

    Abd USG: hepatitis; non

    obstructive jaundice;

    splenomegaly; gall bladder

    sludge with cholecystitis;

    ascites.

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    6/44

    Initial Assessment:

    Hyperthyroid diffuse

    goiter (Graves

    disease) Heart failure (Thyroid

    heart disease)

    Jaundice and liver

    function abnormality

    for evaluation

    Hypokalemia

    Initial Tx:

    High cal high prot diet2100 Cal

    KCl 50 mEq drip in

    500 cc RL for 24h

    KSR tab 1x1

    Multivitamin 3x1

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    7/44

    Progress Note (April 29, 05)

    She complained about bloatedabd, malaise, palpitation,frequent defecation. Weak,conscious, BP 135/65, pulse121x/m irregular, RR 28x/m,temp 37.3. Exophtalmos,

    jaundice, hepatomegaly 3 fgrbac. Fine tremor on hands,mild edema on lower ext.Burch index 55, Wayne index24.

    Ptx: PZ + KCl 75meq/d, PTU

    6x200mg, lugol 4x10gtt,propranolol 4x10mg,dexamethasone 3x1 amp.

    Alb 4.2 g/dL, glob 4.1 g/dL,ALP 208 U/L, HbsAg negative

    FT4 2.6; TSHs 0.012

    Cardiology Dept:

    ECG: atrial fibrillation rhythm

    response ventricle 80-110x/m

    Advice: Digoxin -0-0 tab,

    propranolol 3x20mg po Joint treatment with Cardiology

    Dept.

    Ass: GD with TC + AF + DC +

    jaundice for evaluation

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    8/44

    Progress Note (May 2, 05)

    Decreased abd distention, hepatomegaly 1fgr bac, decreased lower limb edema.

    Burch Index 30 improved thyroid crisis

    Lab: direct bili 13.62 mg/dL, SGOT 192 U/L,SGPT 216 U/L, serum creatinin 1.3 mg/dL.

    Assess: Graves dis with improved thyroidcrisis + DC class I-II + jaundice (susp. Due

    to liver congestion) Ptx: same as previous day; digoxin and dexa

    were discontinued.

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    9/44

    IndexesBURCH INDEX 29/4/06 2/5/06

    Thermoreg dysfunction 5 5

    CNS effect 0 0

    GI dysfunction: jaundice 20 20

    Tachycardia 15 0

    CHF: mild edema 5 5

    AF 10 0

    Precipitants 0 0

    55 30

    WAYNE INDEX:

    Palpitation (+2), lethargy (+2), weight loss (+3), goiter (+3), warm hands (+2),

    AF (+4), pulse >90 (+3), prefer cold (+5)

    Total: 24 hyperthyroidism

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    10/44

    Progress Note (May 3, 05)

    Palpitation +, jaundice +, dysuria +

    Liver: not palpable

    Assess: Graves dis without thyroidcrisis + DC gr 1-2 + susp jaundice due

    to liver congestion + UTI

    Joint treatment with cardio wasterminated

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    11/44

    Progress Note (May 6, 05)

    Jaundice +, dyspnea -, liver/ spleen

    unpalpable, limbs oedema

    Assess: Graves dis + improved DC +

    jaundice

    Jaundice was still persist, although

    heart failure getting better

    Further evaluation: LFT, seromarkers

    for viral hepatitis, abd USG review

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    12/44

    Imaging

    CXR:

    Enlarged heart with CTR 63%,

    cardiac waist straightened

    Pulmo: no infiltrates,phrenicostal sinus sharp

    Abd USG review (10/5):

    no dilatation of IHBD/ EHBD,

    gall bladder not enlarged

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    13/44

    Progress Note (May 10, 05)

    Jaundice +, minimal symptoms

    Bili total 36.1, bili direct 21.91, SGOT194, SGPT 170, ALP 239, K 3.1

    antiHCV -, antiHBc -, anti HAV igM

    Viral infection, billiary obstructionexcluded

    Otherpossible cause: anti-thyroid(PTU) adverse reaction withdrawPTU; replace with thiamazol 1x10mg

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    14/44

    Progress Note (May 13, 05)

    Minimal symptoms, patient getting

    much better clinically; although

    jaundice still persisted

    Px was discharged; advice: outpatient

    tx at Thyroid Outpatient Clinic

    Tx: propranolol 3x20mg, thiamazol

    1x5mg

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    15/44

    I II V VI IX XIII XVI

    Initial Assessment:

    Hyperthyroid diffuse

    goiter (Graves

    disease)

    Heart failure (Thyroid

    heart disease)

    Observation forjaundice and liver

    function disorder

    Hypokalemia

    28/4 29/4 2/5 3/5 6/5 10/5 13/5

    +: palpitation,

    jaundice, malaise,hepatomegaly

    Burch 55, Wayne 24

    AF normal response

    cardio joint tx

    Ass: GD with TC +

    AF + DC + jaundice

    for evaluation

    + jaundice, min limb

    oedema

    Burch 30

    Assess: Graves dis

    with improved

    thyroid crisis + DC

    class I-II + jaundice(susp. Due to liver

    congestion)

    Digoxin, dexa

    stopped

    Palpitation +, jaundice +,

    dysuria +Liver: not palpable

    Assess: Graves dis

    without thyroid crisis + DC

    gr 1-2 + susp jaundice

    due to liver congestion ?+

    UTI

    Joint treatment with cardio

    was discontinued

    Jaundice +, dyspnea -,

    liver/ spleen unpalpable,

    limbs oedema

    Assess: Graves dis +

    improved DC + jaundice

    Jaundice still persisted,

    although heart failure gotbetter

    Further evaluation: LFT,

    seromarkers for viral

    hepatitis, abd USG review

    Jaundice +, minimal symptoms

    antiHCV -, antiHBc -, anti HAVigM

    Viral infection, biliary obstruction

    excluded

    Possible cause: anti-thyroid

    (PTU) adverse reaction

    withdraw PTU; replace with

    thiamazol 1x10mg

    Minimal symptoms,

    patient was getting much

    better clinically; although

    jaundice persisted

    Px was discharged;

    advice: outpatient tx at

    Thyroid ClinicTx: propranolol 3x20mg,

    thiamazol 1x5mg

    Abd USG review: no

    dilatation of IHBD/

    EHBD, gall bladder

    not enlarged

    Echo: mild MR; EF 73%

    Jaundice -; Bil T 2.3, bil D

    1.2, OT 37, PT 26

    (15/11)

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    16/44

    Progress Note

    Bilirubin

    10/52/528/4 13/5 26/10 15/12

    Tx Thiamazol

    25

    20

    36

    20

    2.13

    30

    20

    10

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    17/44

    Discussion

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    18/44

    JAUNDICE

    Pre-hepatic Hepatic Cholestatic

    bilirubin load

    hemolytic

    process

    Unconjugated

    N:

    transaminase,

    ALP

    Transport defect toward

    hepatocyte/ canal

    membrane excretion to

    biliary syst defect reflux

    to circulation Conjugated

    transaminase

    hepatitis: viral, drug

    Defect of gall fluid

    flow to duodenum

    Conjugated

    : ALP, -GT, total

    cholesterol;steatorrhea,

    pruritus: +

    Sherlock & Doley,

    2002

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    19/44

    Jaundice

    Pre-hepatic: unconjugated

    transaminase, ALP: N

    Hepatic:

    Conjugated

    transaminase

    ALP: N

    Cholestatic:

    Conjugated : ALP, -GT, total

    cholesterol

    steatorrhea

    pruritus

    In this patient:

    Jaundice, conjugated

    bilirubin predominant, transaminase, nopruritus

    Hepatic type jaundice

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    20/44

    Graves disease:

    Autoimmune disease

    TSH receptor antibody

    binds to thyroid glands hyper secretion of T3/ T4 THYROTOXICOSIS

    Male: female ratio = 1:7-8

    Susceptibility related tochromosom 6 and CTLA4

    Triad: hyperthyroidism,diffuse goiter, exophtalmos(plus ophtalmopathy,

    pretibial myxedema,acropachy)

    FT4, TSHs

    Netter, 1976

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    21/44

    In this patient:

    diffuse goiter

    exophtalmos

    mild tremor on hands palpitation

    defecation TSHs, FT4

    Atrial fibrillation

    Cardiomegaly

    Hepatomegaly

    Lower limb oedema

    Female

    Hyperthyroidism

    Diffuse goiter Exophtalmos

    TSHs, FT4

    Graves disease

    Cardiac Decompensationrelated to Graves disease

    (Thyroid heart disease)

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    22/44

    Jaundice in GD

    Heart

    Thyroid

    Liver

    Virus

    Drugs

    Thyroid hormon

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    23/44

    Thyroid - Liver

    TH regulate cells BMR

    Interactions of thyroid liver

    Reversible abn if treated

    immediately

    Thyroid hormon

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    24/44

    Thyroid Heart Dis Liver Congestion

    Thyrotoxicosis

    atrial tachyarithmia(AF), heart failure

    (hyperthyroid

    cardiomyopathy)

    Congestive liver

    icterus, hepatomegaly,

    splenomegaly, ascites, mild

    bilirubin/ transaminase

    return to N if CHF treated

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    25/44

    Infections + Drugs

    Viral infection: >50% acute

    hepatitis cases

    Cause: A (most common), B,

    C

    Drug Toxicity:

    direct drug toxicity

    idiosyncrasies

    allergic reaction

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    26/44

    Dx drug-induced hepatitis (Hanson):

    clinical and laboratory evidence ofhepatocellular dysfunction

    the onset of symptoms temporally related to drug therapy no serologic evidence for current infection with hepatitis A or B, CMV or

    EBV

    the absence of an acute hepatic insult such as shock or sepsis

    no evidence of chronic liver disease the absence of other concomitantly administered drugs, especially known

    hepatotoxins the onset of symptoms ranges from two weeks to 6.5 months after

    institution of PTU therapy

    The Intl. Consensus Meeting on Drug-Induced Liver Disorder:

    1. Hepatocellular: ALT >2x upper normal limit (UNL) orR >5

    2. Cholestatic: ALP >2x UNL or R

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    27/44

    In this patient, initially the suspected causeof the jaundice was heart failure with liver

    congestion. But liver dysfunction was notrelieved after the heart failure treated.

    The clinical and laboratory findings fulfilled

    the Hanson criteria for PTU hepatotoxicity.

    Jaundice caused by drug-induced hepatitis(PTU)

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    28/44

    Treatment

    Only few treatments were effective for liverdamage due to drug toxicity

    Active treatment: drug discontinuation,

    symptomatic tx, supportive measure;

    Replacement PTU with MMI still controversy The fact: MMI has fewer minor side effects than PTU

    In this patient:Withdrew PTU & replaced with thiamazol

    Good clinical condition until end of tx

    Evaluation for bili and transaminases (outpx)

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    29/44

    SUMMARY

    A 31 year-old woman presented to ourhospital because ofjaundice. She had previouslybeen diagnosed to suffer from Graves diseaseandreceived PTU for about six months. At

    presentation there were also signs andsymptoms ofatrial fibrillation and heart failure.Assuming that the jaundice was due tocongestive liver associated with heart failure,initial treatment was directed to control that

    condition. But controlling the heart failure did notalleviate the jaundice.

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    30/44

    SUMMARY

    Thorough evaluations to exclude other possiblecauses led us to the conclusion thatpropylthiouracil(PTU) was the culprit drug. We withdrew theoffending drug (PTU) andswitch it to thiamazol. The

    patient got better after several subsequent days.If jaundice encountered in a patient with Gravesdisease, one should considerseveral possiblecauses i.e.: liver abnormality due to thyrotoxicosis,congestive liver due to thyroid heart disease,

    concomitants viral infection, billiary tractabnormality, or other chronic liver diseases, and lastbut not least hepatotoxic effect of anti-thyroid drugs.

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    31/44

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    32/44

    Evaluation for

    pts with

    jau nd ice (Prat t

    & Kaplan, 2004).

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    33/44

    Biliary Sludge

    Biliary sludge may cause complications,including biliarycolic, acute pancreatitis, and acute cholecystitis.

    Clinical conditions and events associated with theformation of biliary sludge include rapid weight loss,

    pregnancy,ceftriaxone therapy, octreotide therapy, andbonemarrow or solid organ transplantation.

    Asymptomatic patients with sludge can be managedexpectantly. If patients with sludge develop symptoms orcomplications, cholecystectomy should be considered

    as the definitive therapy. (Ko,1999)

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    34/44

    Hyperthyroidism

    Common Forms (85-90% of

    cases)

    Radioactive iodine

    uptake over neck

    Diffuse toxic goiter (Graves disease)

    (60-80%)Increased

    Toxic multinodular goiter (Plummer

    disease)(15-20%)Increased

    Thyrotoxic phase of subacute

    thyroiditis (15-20%) Decreased

    Toxic adenoma (3-5%) Increased

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    35/44

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    36/44

    Antithyroid Drugs: Adverse Drugs

    Reactions

    The most common effects (1-5%) :

    allergic reactions of fever, rash,

    urticaria, and arthralgia; occur within the

    first few weeks of treatmentSerious adverse effects (

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    37/44

    Liver damage

    caused by drug toxicity

    Liver damage often caused by drug toxicity,

    including antithyroid drugs

    Mechanism:

    direct drug toxicity after 2 mo tx; dose-

    dependent: transaminase after PTUdiscontinuation

    idiosyncrasies unexpected and

    unpredictable reaction of drugs ~

    hypersensitivity; aberrant drug metabolism; not

    related to allergy

    allergic reaction itchy, rash, arthralgia,

    variable onset; dose-independent

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    38/44

    AIH: Clinical Manifestation

    Range: asymptomatic fulminant hepatic

    failure Symptoms: fatiguability, lethargy, malaise,

    anorexia, nausea, abdominal pain, and itching

    Concomitants: hemolytic anemia, idiopathicthrombocytopenic purpura, type 1 diabetesmellitus, thyroiditis, and ulcerative colitis

    Lab: aminotransferase elevations are morestriking in autoimmune hepatitis than those ofbilirubin and alkaline phosphatase; elevation in

    serum globulins DD/ includes conditions associated with a

    chronic necroinflammatory picture that is oftenaccompanied by fibrosis or cirrhosis

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    39/44

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    40/44

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    41/44

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    42/44

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    43/44

  • 8/22/2019 @Grv Jaundice on Graves Pkb-dr.iza

    44/44