Turkish Journal of Endocrinology and Metabolism, (2003) : 89-91 CASE REPORT
Propylthiouracil-Induced Liver Cirrhosis
Mehmet Dursun* Şerif Yılmaz* Alpaslan Tuzcu** Fikri Canoruc* Mithat Bahçeci**
Dicle University, School of Medicine, Diyarbakir, Turkey
* Department of Gastroenterology
** Department of Endocrinology
Department of Internal Medicine, Division of Endocrinology, Cerrahpaşa Medical Faculty, University of Istanbul, Turkey
A physician of internal medicine had given propylthiouracil to the 22-year-old patient
with hyperthyroidism for 10 months. The patient admitted to our hospital because of
icterus and hepatic failure after the end of this period. There were confusion, obvious
icterus and moderate ascites in physical examination. Laboratory: total bilirubin: 26
mg/dL, direct bilirubin: 16mg/dL, alkaline phosphatase: 300 IU/L, GGT: 50 IU/L, albumin:
2.1 gr/dL, Prothrombin time: 30 sec., alanine aminotransferase: 324 U/L, aspartate
aminotransferase: 216 U/L. Ultrasonography revealed paranchymal heterogeneity of
liver, splenomegaly and moderate ascites. Liver biopsy was compatible with cirrhosis.
Tests for viral hepatitis B, C, and autoimmune markers were all negative. Serum
seruloplasmine level and saturation of transferrin were normal. Kayser-Fleischer ring
was not detected. ERCP was normal. Apart from propylthiouracil, there were no etiologic
factors that explain the liver pathology. Icterus regressed 3 months after the drug was
discontinued. It must be considered that propylthiouracil may lead to hepatic injury,
and liver function tests must be monitorized closely in the treatment period.
Key words: Propylthiouracil, liver cirrhosis
The liver has an important role in thyroid hormone A 22-year-old woman patient with Graves disease
metabolism, and the level of thyroid hormones is had a good health until 1 year ago. When palpitation,
also important to normal hepatic function and heat intolerance and weight loss developed, she
bilirubin metabolism (1). The high serum levels of had admitted to her doctor. The physician had given
aminotransferase, alkaline phosphatase and bilirubin propyltihouracil 300 mg per day for 10 months
may be accompanied by thyroid disease. In rare continuously. Although she suffered from fatigue
cases, patients suffering from hyperthyroidism may and weakness, the patient had not been monitorized
present with signs and symptoms of liver disease for aminotransferase and bilirubin levels. The drug
(2). However, propylthiouracil, which is the most was discontinued due to the development of icterus
commonly used antithyroid agent, may cause at the end of this time. The patient admitted to our
transient and asymptomatic subclinical liver injury intensive care unit as confusion developed 40 days
(3), and it is reported that it can induce severe after the drug was discontinued. There were
hepatic injury in some cases (4-9). In the present confusion, icterus in skin and scleras, grade II
report, we described a patient with PTU-induced ascites in abdomen and splenomegaly in physical
severe hepatic injury, by drawing attention to examination. In the laboratory examination, serum
hepatotoxicity. total bilirubin was found to be 26 mg/dL, direct
bilirubin 16mg/dL, alkaline phosphatase 300 IU/L,
gama-glutamyl transpeptidase 50 IU/L, albumin
Correspondence address: 2.1 gr/dL, prothrombin time 30 second, alanine
Mehmet Dursun aminotransferase 324 U/L, aspartate aminotrans-
Dicle University, School of Medicine, Department of
Gastroenterology, 21280, Diyarbakir, Turkey
ferase 216 U/L, lactate dehidrogenase 284 IU/L,
Tel : 0 412 248 80 01 – 44 10 glucose 110 mg/dL, sodium 132 mEq/L, potassium
Fax : 0 412 248 85 20
e-mail : firstname.lastname@example.org
3.2 mEq/L. In addition, hematocrit was 30%,
hemoglobin 11 gr/dL, platelet 176.000 /µL, white persist for years (4,9). Treatment with PTU can
blood cell 9600 /mm3, prothrobin time 30 second cause acute hepatocellular necrosis, whereas
(INR:2.3), serum ascites-albumin gradient 1.2, methimazole and carbimazole are potential causes
ascidic fluid cell count 100 cell/mm3. ANA, ASMA, of cholestatic jaundice (11). Chronic hepatitis (chronic
anti-LKM1, AMA-M2, pANCA, CMV, EBV, HBV parenchimal injury) can be a manifestation of the
and HCV markers were negative. Serum cerulo- hepatotoxicity caused by certain drugs. Propyl-
plasmin and alpha 1 antitripsin levels, saturation of thiouracil is one of the examples that can cause this
transferrine were normal. In the eye examination, reaction. It is difficult to distinguish from chronic
Kayser-Fleischer ring was not detected. Thyroid- viral hepatitis. It may also mimic autoimmune
stimulating hormone level was 0.32 µU/mL, and hepatitis in which severe liver damage with
thyrotropin releasing hormone stimulating test was prominent plasma cell infiltration may be present
normal. Ultrasonography revealed paranchymal hetero- (12). The mechanism of PTU-induced hepatic
geneity of liver, splenomegaly (long axis: 153 mm) injury is not fully understood, although it may
and moderate ascites. The bile tree was normal in result from a hypersensitivity reaction (11).
ERCP. Liver biopsy was performed after intensive
Our patient was taken into PTU therapy because of
fresh frozen plasma transfusion, and histological
hyperthyroidism. However, she had not been
finding was found to be compatible with cirrhosis.
monitorized in terms of liver function tests. After
The patient was in hepatic encephalopathy based icterus and confusion developed, hepatotoxicity
on liver cirrhosis (Child B Score 8), and lactulose, was considered, and then the patient admitted to
fresh frozen plasma, paranteral fluid replasman our clinic. Because of hepatic encephalopathy,
therapy was given. The conscious became normal intensive supportive treatment was given to the
after 3 days. Then, cholestyramine, ursodeoxycholic patient, and clinical recovery occurred. It was
acid and prednisolone (60 mg per day) were added understood that she had cirrhosis after liver biopsy.
to treatment regimen. Because of the worsening of
mental status and laboratory data, prednisolone For differential diagnosis, first of all there was not
was withdrawn from therapy regimen. The ascites alchol consumption or any herb intake in her
regressed at the follow-up. Despite the decrease in history. Hepatitis serology testing for hepatitis A,
serum bilirubin level to 3 mg/dL, the amino- B, C, Epstein Barr Virus, and Cytomegalovirus
transferase levels did not change significantly. The was negative. HCV RNA was also negative. There
aminotransferase levels were still 3 fold higher was no histological evidence of viral or auto-
than normal in the last 5 month-follow-up periods. immune hepatitis or alpha-1 antitrypsin deficiency.
Primary biliary cirrhosis and primary sclerosing
Discussion cholangitis were ruled out by means of specific
Hepatotoxicity is a well-described but rare antibody and ERCP procedure. Serum cerulo-
complication of antithyroid drugs. Propylthiouracil plasmin level, urinary copper level, and transferrine
is the most commonly used antithyroid drug. saturation were normal, so we ruled out Wilson
disease and haemochromatosis. Viral hepatitis,
Transient and asymptomatic subclinical liver
autoimmune hepatitis, primary biliary cirrhosis,
injury may develop during PTU therapy. Liaw et
primary sclerosing cholangitis, Wilson disease,
al. reported that hepatotoxicity occurs in 28% of
haemochromatosis and α1 antitripsin deficiency
the patients using PTU. Despite continued PTU
were excluded in etiologic examinations. The drug-
therapy at a reduced dose, ALT levels returned to
induced lymphocyte stimulating test might be
normal in the most of the patients in the following
useful for distinguishing it from other etiologic
3 months (3). Nevertheless, it should be kept in
factors. Besides it was used in some of the reports
mind that severe, irreversible and fatal hepato-
about this subject (5, 8 ). This test is constituted on
toxicity may occur during PTU therapy (5-9).
sensitization of the patient’s lymphocytes to PTU.
Despite its widespread use, there are only a few
We could not manage performing this test in spite
reported cases of PTU-induced severe hepatotoxicity
of our all efforts.
(9). PTU-induced severe liver injury is seen in 0.6
percent of the patients (10). Injury may occur In the follow-up, although a significant decrease
months after taking PTU, and this problem may was observed in serum bilirubin levels, there was
no significant change in aminotransferase levels. 5. Ichiki Y, Akahoshi M, Yamashita N, Morita C, Maruyama
T, Horiuchi T, Hayashida K, Ishibashi H, Niho Y. Propyl-
Since TRH test was normal and there were not any
thiouracil-induced severe hepatitis: a case report and
signs and symptoms of hyperthyroidism, high review of the literature. J Gastroenterol 33: 747-50, 1998.
levels of aminotransferase were attributed to PTU
6. Limaye A, Ruffolo PR. Propylthiouracil-induced fatal
toxicity. The aminotransferase levels were still 3 hepatic necrosis. Am J Gastroenterol 82: 152-4, 1987.
fold higher than normal in the last 5 month-follow-
7. Deidiker R, deMello DE. Propylthiouracil-induced fulminant
up period. The patient is still being followed up hepatitis: case report and review of the literature. Pediatr
periodically. Pathol Lab Med 16: 845-52, 1996.
The present case is considerably notable for PTU- 8. Mihas AA, Holley P, Koff RS, Hirschowitz BI. Fulminant
induced liver cirrhosis. In the light of these results, hepatitis and lymphocyte sensitization due to propylthiouracil.
Gastroenterology 70(5 PT.1): 770-4, 1976.
it is clear that all patients under antithyroid therapy
should be monitorized in terms of hepatotoxicity. 9. Ozenirler S, Tuncer C, Boztepe U, Akyol G, Alkim H,
Cakir N, Kandilci U. Propylthiouracil-induced hepatic
damage. Ann Pharmacother 30: 960-3, 1996.
10. Frenkel J, Tellez R, Reyes C, Gonzalez G, Michaud P.
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