Fulminant Hepatitis A in a Patient with Severe Hyperthyroidism: Rapid Recovery from Hepatic Coma after Plasmapheresis and Total Thyroidectomy

A 62-yr-old Chinese man was transferred to the medical intensive care unit of our university hospital because of hepatic coma and severe hyperthyroidism. The software engineer, who had lived in Germany for 10 yr, had been well until 3 days before admission, when he experienced acute onset of nausea, vomiting, and diarrhea. The next day, he started passing black, tarry stools. Jaundice, low-grade fever, and pronounced malaise developed. Three days after onset of symptoms he was admitted to another hospital, where gastroscopy showed diffuse gastric bleeding due to erosive gastritis. He was treated with ranitidine and metoclopramide iv. The laboratory investigations at admission (Table 1) showed markedly elevated liver enzymes, a prolonged prothrombin time, and decreased serum levels of antithrombin III and total protein. Glucose, electrolytes, blood urea nitrogen, creatinine, creatine phosphokinase, amylase, lipase, uric acid, complete blood count (with the exception of a reduced platelet count), and erythrocyte sedimentation rate were within the normal range. Serologic tests for antibodies against hepatitis A (IgG and IgM) were positive, and the patient showed marked hyperthyroidism (Table 1). Thyroid scintiscanning revealed a diffusely increased thyroid Tc-pertechnetate uptake without evidence for hyperfunctioning nodules. Diffuse goiter with an irregular and slightly hypoechoic structure was diagnosed by thyroid sonography. The patient received 40 mg methimazole per day iv. The coagulopathy was treated with 10 mg phytonadione (vitamine K1) per day iv and by infusion of a total of 400 mL fresh-frozen plasma. The patient had been weak and drowsy on admission to the other hospital, but was able to communicate. He was oriented to time, place, and self. However, his mental status rapidly deteriorated. Hepatic encephalopathy with confusion developed, and he showed increased psychomotor activity. No focal neurologic signs were noted. A cerebral computed tomography scan (without administration of iodine containing contrast medium) was normal. A central line was inserted, and the patient received glucose, an amino acid solution enriched with branched amino acids, electrolyte solutions, and ornithine aspartate iv. For sedation, midazolam, flunitrazepam, and morphine sulfate were administered iv. The following day, the patient was in a deep coma, and he was transferred to our university hospital. The patient’s wife reported a history of mild Graves’ disease for 5 yr. The patient had refused radioiodine therapy or thyroidectomy and had been taking oral methimazole irregularly for 2 yr, although repeatedly serum T4 levels were markedly elevated and thyrotropin was undetectable in serum. His general practitioner had recommended a dose of 20 mg methimazole per day. Due to compliance problems, he also did not follow the recommendation to minimize his iodine intake, but continued to eat seafood regularly. However, administration of iodine containing x-ray contrast medium in the previous months could be ruled out as a predisposing factor for the development of his thyrotoxicosis. Furthermore, atrial fibrillation was present for 5 yr before admission. The patient repeatedly refused digoxin treatment, cardioversion, or anticoagulation for this condition. However, he was able to work hard up to 12 h a day and had just arrived from a 4-week business trip to southern China and Beijing 1 month before the onset of his current illness. His German business partner, who accompanied the patient during the whole trip to China, as well as his wife and daughter, stayed well. There was no known history of contact with persons infected with hepatitis A. The patient drank one to two bottles of beer a day. He did not take acetaminophen or other potentially hepatotoxic drugs, apart from methimazole. He had never had symptoms suggestive of hepatitis or other liver diseases and had never been hospitalized before. Three months before admission, liver function tests had been normal, but hyperthyroidism was present. On arrival in our intensive care unit, the jaundiced and dehydrated patient was deeply comatose (Glasgow coma scale, 3/15) and did not show any reaction to painful stimuli. He was breathing spontaneously, and his respirations were 28/min. His rectal temperature was 36.3 C (96.7 F), the blood Received October 13, 1999. Revision received December 1, 1999. Accepted December 6, 1999. Address correspondence and requests for reprints to: Michael Enghofer, M.D., Department of Medicine I, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. 0021-972X/00/$03.00/0 Vol. 85, No. 5 The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A.