@Grv Jaundice on Graves Pkb-dr.iza
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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
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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
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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.
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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
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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.
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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
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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
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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.
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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
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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
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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
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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
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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
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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
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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)
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Progress Note
Bilirubin
10/52/528/4 13/5 26/10 15/12
Tx Thiamazol
25
20
36
20
2.13
30
20
10
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Discussion
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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
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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
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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
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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)
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Jaundice in GD
Heart
Thyroid
Liver
Virus
Drugs
Thyroid hormon
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Thyroid - Liver
TH regulate cells BMR
Interactions of thyroid liver
Reversible abn if treated
immediately
Thyroid hormon
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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
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Infections + Drugs
Viral infection: >50% acute
hepatitis cases
Cause: A (most common), B,
C
Drug Toxicity:
direct drug toxicity
idiosyncrasies
allergic reaction
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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
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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)
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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)
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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.
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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.
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Evaluation for
pts with
jau nd ice (Prat t
& Kaplan, 2004).
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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)
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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
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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 (
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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
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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
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