A 71-year-old Caucasian male was admitted to the outpatient nephrology clinic with the complaints of general malaise, progressive asthenia, weight loss, loss of appetite, jaundice, and decrease in urine volume. On admission, blood pressure was 120/70 mm/Hg; the pulse rate was regular 95/min. He was pale, icteric and dehydrated. On physical examination, no abnormalities were found except hepatosplenomegaly and also multiple nodules in his thyroid glands. He had a history of subclinical hyperthyroidism and hypertension for about 30 years and treated with PTU irregularly, carvedilol (12.5 mg/day), and trimetazidine (60 mg/day). The patient was hospitalized for further investigation.
As it is shown in Tables 1 and 2, he showed normokrom normositer anemia pancytopenia, cholestasis, and subclinical hyperthyroidism in his laboratory examination.
Ultrasonographic examination and magnetic resonance imaging (MRI) of abdomen were performed to exclude extrahepatic cholestasis and showed no clues for malignancies but heterogeneity of liver parenchyma; intra- and extrahepatic bile duct sizes were normal; enlargement of liver (170 mm) and spleen (188 mm) were observed; in addition, portal and splenic vein diameters were increased. Heart failure and the other rare causes of intrahepatic cholestasis were also excluded. Pathological examination of liver biopsy showed that there was sparse piece-meal necrosis and inflammatory cell infiltration in the portal areas. Focal ductuli proliferation, pericentral intracytoplasmic bile pigments, bile plugs, and diffuse focal necrosis were also noted (Figure 1). Histopathological findings were interpreted as intrahepatic cholestasis might be related to thyrotoxicosis.
Serological markers, autoantibodies, laboratory findings, and liver biopsy findings helped us to exclude primary biliary cirrhosis, autoimmune hepatitis, Wilson's disease, hemochromatosis, and viral hepatitis.
On his 14th day of hospitalization, tachycardia, elevated blood pressure, tachypnea, agitation, and dysphonia were observed. His renal function was deteriorated and hemodialysis treatment was initiated.
Since PTU and methimazole treatments have been reported to be related with AASV, we decided to perform radioactive iodine (131I-10 mCi) treatment on 27th day of admittance for hyperthyroidism. After the RAI treatment, patient became euthyroid but cholestasis was not ameliorated. Ursodeoxycholic acid (1500 mg/day) and rifampicin (600 mg/day) treatments also did not bring any further benefit in point of cholestasis.
Patient was pancytopenic on his admittance and during the follow-up; haematological examination and bone marrow biopsy showed no significant pathology. Serum and urine immune fixation electrophoresis were performed to exclude multiple myeloma, a possible cause of anemia/pancytopenia in the elderly. Moreover, rectal biopsy was negative for the amyloidosis, which might be possible explanation for the hepatosplenomegaly, kidney failure, and pancytopenia as well. And it was concluded that pancytopenia might be related to hypersplenism.
Because the patient had suffered from dysphonia and dyspnea, thorax computerized tomography (CT) was performed and several nodules were discovered in right lung parenchyma (Figure 2); the right apicoposterior one was cavitary; nevertheless, pneumonia, tuberculosis, and malignancies were excluded. These findings supported lung involvement of ANCA positive vasculitis.
After exclusion of all of these possibilities, we concluded that the patient was suffering from hyperthyroidism induced intrahepatic cholestasis. Furthermore, since hyperthyroidism was not taken under control for many years, the changes in the liver became permanent and leading to developed cirrhosis eventually. In addition, we thought that using PTU treatment irregularly to control hyperthyroidism caused ANCA positive vasculitis with renal and lung involvement.