Increased Liver Enzyme Levels Research Articles

Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B

Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder. We infused a single dose of a serotype-8-pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein in six patients with severe hemophilia B (FIX activity, <1% of normal values). Study participants were enrolled sequentially in one of three cohorts (given a high, intermediate, or low dose of vector), with two participants in each group. Vector was administered without immunosuppressive therapy, and participants were followed for 6 to 16 months. AAV-mediated expression of FIX at 2 to 11% of normal levels was observed in all participants. Four of the six discontinued FIX prophylaxis and remained free of spontaneous hemorrhage; in the other two, the interval between prophylactic injections was increased. Of the two participants who received the high dose of vector, one had a transient, asymptomatic elevation of serum aminotransferase levels, which was associated with the detection of AAV8-capsid-specific T cells in the peripheral blood; the other had a slight increase in liver-enzyme levels, the cause of which was less clear. Each of these two participants received a short course of glucocorticoid therapy, which rapidly normalized aminotransferase levels and maintained FIX levels in the range of 3 to 11% of normal values. Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects. Although immune-mediated clearance of AAV-transduced hepatocytes remains a concern, this process may be controlled with a short course of glucocorticoids without loss of transgene expression. (Funded by the Medical Research Council and others; ClinicalTrials.gov number, NCT00979238.).

Assessment of the extent of oxidative stress induced by intravenous ferumoxytol, ferric carboxymaltose, iron sucrose and iron dextran in a nonclinical model

Intravenous (i.v.) iron is associated with a risk of oxidative stress. The effects of ferumoxytol, a recently approved i.v. iron preparation, were compared with those of ferric carboxymaltose, low molecular weight iron dextran and iron sucrose in the liver, kidneys and heart of normal rats. In contrast to iron sucrose and ferric carboxymaltose, low molecular weight iron dextran and ferumoxytol caused renal and hepatic damage as demonstrated by proteinuria and increased liver enzyme levels. Higher levels of oxidative stress in these tissues were also indicated, by significantly higher levels of malondialdehyde, significantly increased antioxidant enzyme activities, and a significant reduction in the reduced to oxidized glutathione ratio. Inflammatory markers were also significantly higher with ferumoxytol and low molecular weight iron dextran rats than iron sucrose and ferric carboxymaltose. Polarographic analysis suggested that ferumoxytol contains a component with a more positive reduction potential, which may facilitate iron-catalyzed formation of reactive oxygen species and thus be responsible for the observed effects. Only low molecular weight iron dextran induced oxidative stress and inflammation in the heart.

Use of pegylated interferon in hypereosinophilic syndrome

Scant information exists about pegylated interferons (PEG-IFNs) use for treating hypereosinophilic syndrome (HES). We describe 6 patients with HES—1 patient with a newly identified chromosomal abnormality—who received PEG-IFNs. PEG-IFN alpha-2b replaced interferon (IFN) alpha-2b for 4 patients and was initial treatment of 2 patients. PEG-IFN alpha-2a was substituted when PEG-IFN alpha-2b became unavailable. PEG-IFNs were well tolerated and controlled eosinophilia. The dose of PEG-IFNs often could be tapered and the interval between doses lengthened beyond 7days. Adverse effects included dose-related increases in liver enzyme levels, hair loss, mild lymphopenia, and neutropenia. PEG-IFNs are effective treatment of HES.

Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study

Objective To evaluate the association between non-alcoholic fatty liver disease and all cause and cause specific mortality in a representative sample of the US general population.Design Prospective cohort study.Setting US...

Kronik Hepatitte Serum Transaminaz Değerleri ile Fibrozis Evrelemesi ve Nekroinflamatuar Aktivite Skorlarının İlişkisi

Objective: The aim of this study is to compare the necroinflammatory activity score / histological activity index (HAI) and fibrosis score detected in liver biopsies with serum transaminase levels of chronic hepatitis B, C and steatohepatitis. Material and Methods: This retrospective study included total of 398 cases whose liver biopsies were performed because increased liver enzyme levels and had the diagnoses of chronic hepatitis B, hepatitis C or steatohepatitis ofter liver biopsy between 2003-2007. The HAI and fibrosis scores of all cases were evaluated according to ISHAK classification criteria and then the results were compared with the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at the time of biopsy. Results: When all cases were considered, serum AST values emerged as the most statistically significant variable for hepatic fibrosis (r:0.311; p<0.01). Additionally, there was a correlation between AST values and HAI (r:0.295; p<0.01). On the other hand, serum ALT values did not correlate with (r:0.094; p>0.05) the extent of hepatic fibrosis but correlated weakly with HAI (r:0.242; p<0.01). Conclusion: Serum AST level is found to be a significant indicator of histological activity index and fibrosis as well as hepatic damage. These findings suggested that, among other factors, serum AST values should be considered in decisions regarding the need for liver biopsy and treatment in patients with chronic hepatitis.

Fingolimod for relapsing multiple sclerosis: an update

Importance of the field: Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the CNS. There is a large unmet need for new disease-modifying therapies with improved convenience, safety and efficacy. Fingolimod is an oral sphingosine-1-phosphase (S1P) receptor modulator under clinical investigation for the treatment of relapsing-remitting and primary progressive MS.Areas covered in this review: This review provides an update on the mechanism of action, pharmacological properties and efficacy and safety of fingolimod in patients with relapsing MS, with a particular emphasis on clinical trials.What the reader will gain: The reader will gain a comprehensive overview of the mechanism of action of fingolimod, particularly how the drug inhibits lymphocyte egress from secondary lymphoid organs by modulation of S1P receptors, and its pharmacokinetic and pharmacodynamic properties. Results from Phase II studies and pivotal Phase III trials of fingolimod for relapsing MS are discussed in depth.Take home message: Randomized clinical trials have demonstrated the superior efficacy of fingolimod in reducing relapse rates and MRI measures of disease activity, as compared with placebo and intramuscular IFN-β-1a. Fingolimod also lowered the risk of disability progression compared with placebo. Adverse events included bradycardia and atrioventricular block, respiratory and herpesvirus infections, increased liver enzyme levels, hypertension and macular edema. Fingolimod 0.5 mg seems to provide the best risk–benefit ratio.

Detective Work in Drug-Induced Liver Injury: Sometimes It Is All About Interviewing the Right Witness

Diagnosing drug-induced liver injury (DILI) relies primarily on history taking. We report 4 cases in which DILI was missed or the drug was misidentified when physicians relied solely on patient history. We reviewed 27 cases referred with possible DILI from August 1, 2009, to February 1, 2010. Four patients seemed to be reliable historians, but their cases were greatly clarified by a call to their pharmacist. One subject, who forgot a new medication, underwent an unfruitful evaluation including surgery. Another patient had acetaminophen toxicity that was missed because she grossly underreported her pain medication use. The third and fourth patients forgot taking amoxicillin/clavulanate, so other agents mistakenly were implicated. Roussel Uclaf Causality Assessment Method scores were 8 (probable) or 9 (highly probable) for all 4 cases. Without pharmacy input, DILI was missed in 2 cases and the wrong agent was implicated twice. Reviewing pharmacy records can be crucial for patients and DILI research. We recommend calling the pharmacist directly for increased liver enzyme levels of unclear source or suspected DILI regardless of patient history.

Heme oxygenase (HO)-1 protects from lipopolysaccharide (LPS)-mediated liver injury by inhibition of hepatic leukocyte accumulation and improvement of microvascular perfusion

Lipopolysaccharide (LPS) represents a highly toxic substance which may aggravate morbidity and mortality in septic diseases. A recent study has reported that the induction of heme oxygenase (HO)-1 protects from LPS-induced liver injury. The mechanisms of action however, have not been clarified yet. Therefore, we analyzed in vivo the effects of HO-1 on the liver microcirculation under conditions of LPS exposure. In C57BL/6 mice, endotoxemia was induced by intraperitoneal (i.p.) administration of LPS (500 microg/kg) and D-galactosamine (Gal, 800 mg/kg). HO-1 was induced in vivo by pretreatment with hemin dissolved in DMSO (50 micromol/kg i.p.). Animals treated with DMSO only served as controls. Six hours after LPS exposure the hepatic microcirculation and leukocyte-endothelial cell interaction were analyzed by intravital fluorescence microscopy. HO-1 expression was determined by Western blot analysis. Hepatocellular damage was assessed by measuring the serum levels of aspartate aminotransferase and alanine aminotransferase. In addition, leukocyte transmigration and hepatocellular apoptosis were analyzed by histology and immunohistochemistry. In controls, LPS/Gal caused severe liver injury, as indicated by increased liver enzyme levels and apoptotic cell death. This was associated with distinct sinusoidal perfusion failure and microvascular intrahepatic leukocyte accumulation. Of interest, induction of HO-1 significantly reduced numbers of adherent and extravascular leukocytes when compared to controls. Moreover, microvascular perfusion was significantly improved, resulting in a decrease of AST and ALT and a reduction of hepatocellular apoptosis. Our novel data indicate that induction of HO-1 protects the liver from LPS-mediated injury by reducing leukocytic inflammation and improving intrahepatic microcirculation.

Association Between Posttraumatic Stress Disorder Following Myocardial Infarction and Liver Enzyme Levels: A Prospective Study

Research in rodents demonstrated that psychological stress increases circulating levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase reflecting liver injury. Moreover, chronic posttraumatic stress disorder and transaminases predicted coronary heart disease. To investigate the hypothesis that severity of posttraumatic stress disorder following myocardial infarction would prospectively relate to liver enzymes. Study participants were 24 patients (mean 59+/-7 years, 79% men) with an interviewer-rated diagnosis of posttraumatic stress disorder caused by an index myocardial infarction 3+/-3 months before. After a mean follow-up of 26+/-6 months, patients had a clinical interview to reassess posttraumatic stress disorder severity, a medical history, and blood collected to determine liver enzymes. Total posttraumatic stress disorder symptoms assessed at study entry prospectively predicted plasma levels of alanine transaminase (r=.47, p=.031) and alkaline phosphatase (r=.57, p=.004), but not of aspartate transaminase (p=.15), controlling for follow-up duration and antidepressant use. Total posttraumatic stress disorder symptoms assessed at follow-up were associated with alanine transaminase (r=.72, p=.004), aspartate transaminase (r=.60, p=.018), and alkaline phosphatase (r=.64, p=.001) in the 16 patients who had maintained diagnostic posttraumatic stress disorder, but not in all 24 patients. The severity of posttraumatic stress disorder following myocardial infarction was associated with mild increase in liver enzyme levels, suggesting that chronic psychological stress relates to hepatic damage in humans. This might help to explain the previously observed increased cardiovascular risk in chronically traumatized individuals.

Liver enzyme abnormalities in systemic lupus erythematosus: a focus on toxic hepatitis

Although subclinical liver disease is common in systemic lupus erythematosus (SLE), strikingly high levels of liver enzymes are rare. Our aim was to determine the cause of high levels of liver enzymes in lupus patients, particularly in patients diagnosed with toxic hepatitis. We performed a retrospective chart review of SLE patients treated at the Inje University Hospital between 2001 and 2008. We defined liver enzyme abnormality as a twofold or greater increase in two or more of the following four components: total bilirubin, AST, ALT and LDH or ALP. Acute toxic hepatitis was diagnosed by a score ≥ 5 in the Roussel Uclaf Causality Assessment Method. Of 141 SLE patients 46 (32.6%) met strict criteria for the liver enzyme abnormality. In total, 11 patients (7.8%) in this study had presumed toxic hepatitis associated with either herbal medicines (n = 6), anti-tuberculosis medications (n = 3), antibiotics (n = 1) or valproic acid (n = 1). There were striking laboratory abnormalities in the groups diagnosed with toxic hepatitis (mean peak values: AST 775 ± 464 U/L, ALT 400 ± 447 U/L, ALP 767 ± 408 U/L, LDH 1,469 ± 779 U/L). All six patients with herbal-induced toxic hepatitis were in the active SLE state. After cessation of the suspected causative medication and subsequent administration of steroids, liver enzyme levels were improved. Herbal medicines and anti-tuberculosis medications, known to cause toxic hepatitis, can also induce increased liver enzyme levels in lupus patients. However, since most herbal medicines contain a mixture of various products, we could not ascertain what specific ingredient induced the increase in liver enzyme levels.

Validation of a Prediction Rule for the Identification of Children With Intra-abdominal Injuries After Blunt Torso Trauma

We validate the accuracy of a previously derived clinical prediction rule for the identification of children with intra-abdominal injuries after blunt torso trauma. We conducted a prospective observational study of children with blunt torso trauma who were evaluated for intra-abdominal injury with abdominal computed tomography (CT), diagnostic laparoscopy, or laparotomy at a Level I trauma center during a 3-year period to validate a previously derived prediction rule. The emergency physician providing care documented history and physical examination findings on a standardized data collection form before knowledge of the results of diagnostic imaging. The clinical prediction rule being evaluated included 6 "high-risk" variables, the presence of any of which indicated that the child was not at low risk for intra-abdominal injury: low age-adjusted systolic blood pressure, abdominal tenderness, femur fracture, increased liver enzyme levels (serum aspartate aminotransferase concentration >200 U/L or serum alanine aminotransferase concentration >125 U/L), microscopic hematuria (urinalysis >5 RBCs/high powered field), or an initial hematocrit level less than 30%. One thousand three hundred twenty-four children with blunt torso trauma were enrolled, and 1,119 (85%) patients had the variables in the decision rule documented by the emergency physician and therefore made up the study sample. The prediction rule had the following test characteristics: sensitivity=149 of 157, 94.9% (95% confidence interval [CI] 90.2% to 97.7%) and specificity=357 of 962, 37.1% (95% CI 34.0 to 40.3%). Three hundred sixty-five patients tested negative for the rule; thus, strict application would have resulted in a 33% reduction in abdominal CT scanning. Of the 8 patients with intra-abdominal injury not identified by the prediction rule, 1 underwent a laparotomy. This patient had a serosal tear and a mesenteric hematoma at laparotomy, neither of which required specific surgical intervention. A clinical prediction rule consisting of 6 variables, easily available to clinicians in the ED, identifies most but not all children with intra-abdominal injury. Application of the prediction rule to this sample would have reduced the number of unnecessary abdominal CT scans performed but would have failed to identify 1 child undergoing (a nontherapeutic) laparotomy. Thus, further refinement of this prediction rule in a large, multicenter cohort is necessary before widespread implementation.

Editorial Commentary:The Mystery of Hepatitis E Seroprevalence in Developed Countries: Is There Subclinical Infection due to Hepatitis E Virus?

<i>Editorial Commentary:</i>The Mystery of Hepatitis E Seroprevalence in Developed Countries: Is There Subclinical Infection due to Hepatitis E Virus?

Elucidating Rifampin's Inducing and Inhibiting Effects on Glyburide Pharmacokinetics and Blood Glucose in Healthy Volunteers: Unmasking the Differential Effects of Enzyme Induction and Transporter Inhibition for a Drug and Its Primary Metabolite

The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its primary metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.

Adverse effects of ketoconazole in dogs – a retrospective study

Although ketoconazole has been used extensively in dogs for the treatment of various fungal infections, information about adverse effects is mainly anecdotal. Common adverse effects in humans include dose-dependant anorexia, nausea and vomiting, allergic rashes and pruritus. Drug-induced hepatitis is very rare, but potentially fatal. The aim of this study was to evaluate the type and frequency of adverse effects associated with ketoconazole therapy in dogs treated for skin diseases and any possible influence of dosage, duration of therapy, signalment or concurrent medication. The medical records of 632 dogs treated with ketoconazole (2.6-33.4 mg/kg) were reviewed. Adverse effects occurred in 14.6% (92 dogs) and included vomiting (7.1%), anorexia (4.9%), lethargy (1.9%), diarrhea (1.1%), pruritus (0.6%), erythema (0.3%) and other adverse effects (2.5%). Of the dogs with other adverse effects, four of 16 (25%) were ataxic and three of these received concurrent ivermectin. Adverse effects were significantly more often recorded in dogs concurrently treated with ciclosporin (P = 0.034) or ivermectin (P = 0.007). Increased liver enzyme levels were reported rarely, and icterus was not seen in any of the dogs. However, monitoring liver enzymes during therapy is recommended, although this might not necessarily prevent severe idiosyncratic hepatotoxicity.

Nationwide survey to compare the prevalence of transient elevation of liver transaminase during treatment of diabetic ketosis or ketoacidosis in new-onset acute and fulminant type 1 diabetes mellitus

Background aims. A mild increase in liver enzyme levels is sometimes observed in patients with diabetic ketosis or ketoacidosis. The aim of the present study was to assess the cause and prevalence of the elevation of liver transaminase levels in fulminant and acute-onset type 1 diabetic patients experiencing diabetic ketosis or ketoacidosis.Methods. We analyzed data on the liver transaminase levels of 108 patients over 18 years of age with newly diagnosed type 1 diabetes complicated by ketosis or ketoacidosis. The data were collated from a nationwide survey on fulminant type 1 diabetes and retrospective medical records.Results. Thirty-two (60.4%) out of the 53 patients suffering from fulminant type 1 diabetes were detected with transient elevation of liver transaminase (TELT) levels during the first month after initiation of insulin therapy; in the case of acute-onset type 1 diabetes, such an observation was noted in 16 (29.1%) out of 55 patients. Fatty liver was diagnosed in 20% of the patients, and 65% of these patients exhibited TELT. The dosage of insulin injected in these patients was significantly high.Conclusions. High blood glucose and fatty liver may influence the elevation of liver transaminase levels during the treatment of new-onset type 1 diabetes.

Elevated Serum Aminotransferase Levels in Children at Risk for Obstructive Sleep Apnea

Fatty liver disease (FLD) is a highly prevalent condition in obese (Ob) children, who are at increased risk for obstructive sleep apnea (OSA). However, the contribution of OSA to FLD remains unknown. Prospective study. Polysomnographic evaluation and assessment of plasma levels of insulin, glucose, and lipids, and liver function tests. A total of 518 consecutive snoring children 4 to 17 years of age who were being evaluated for habitual snoring and suspected OSA. A total of 376 children had body mass index z score of < 1.20 (non-Ob children), 3 children (<1%) had elevated serum aminotransferase (LFT) levels, and 248 had OSA (65.9%). Among the 142 overweight/Ob children, 46 had elevated LFT levels (32.4%); of these children, 42 had OSA (91.3%). In contrast, OSA was present in only 71.8% of Ob children without elevated LFT level (p < 0.01). Insulin resistance and hyperlipidemia were more likely to occur in children with FLD. Furthermore, FLD was improved after treatment of OSA in 32 of 42 Ob children (p < 0.0001). Increased liver enzyme levels are frequently found in Ob snoring children, particularly among those with OSA and/or metabolic dysfunction. Effective treatment of OSA results in improved liver function test results in the vast majority of these patients.

Löfgren Syndrome and Peritoneal Involvement by Sarcoidosis: Case Report

An unusual case of a patient with Löfgren syndrome peritoneal involvement by sarcoidosis.A 36-year-old woman presented with Löfgren syndrome and an increase in liver enzyme levels. An abdominal CT scan showed multiple nodules on the peritoneum mimicking peritoneal carcinomatosis. Laparoscopy was conducted with biopsy of the peritoneal nodules.Biopsy specimens from the peritoneum, liver, and bronchi showed noncaseating granulomas, and the search for tuberculosis was negative. Clinical and biological features resolved within 6 months, without therapy with steroids, while a thoracic CT scan as well as an abdominal CT scan showed no change.To our knowledge, this is the first reported case of peritoneal sarcoidosis associated with Löfgren syndrome. A longer follow-up will, however, be required to assess the chronicity of the disease.

The Clinical Relevance of Compound Heterozygosity for the C282Y and H63D Substitutions in Hemochromatosis

Two major mutations are defined within the hemochromatosis gene, HFE. Although the effects of the C282Y substitution have been well characterized, the clinical significance of the C282Y/H63D state remains unclear. This study assessed the phenotypic expression in C282Y/H63D subjects as compared with C282Y homozygotes. Data were obtained from 91 C282Y/H63D probands, 158 C282Y/H63D subjects identified through family screening, and 483 C282Y homozygotes. Subjects underwent clinical evaluation, genotyping, biochemical assessment, and liver biopsy examination where clinically indicated. C282Y/H63D probands had significantly less clinical and biochemical expression than C282Y homozygotes. Biochemical expression was higher in C282Y/H63D probands than in C282Y/H63D subjects identified through family screening (P < .001). Of the C282Y/H63D subjects with serum ferritin levels greater than 1000 mug/L, all had known comorbid factors that could have contributed to the increased ferritin level. Of the 51 C282Y/H63D subjects who underwent liver biopsy examination, significantly increased iron stores were present in 9 subjects and hepatic fibrosis was present in 13. Twelve of the 13 had evidence of hepatic steatosis, excess alcohol consumption, or diabetes. The mobilizable iron level was significantly higher in C282Y homozygous males than in compound heterozygous males (P < .001). Genetic screening of C282Y/H63D first-degree relatives detected 5 C282Y homozygotes. C282Y/H63D subjects referred for assessment had a high prevalence of increased iron indices but did not develop progressive clinical disease without comorbid factors such as steatosis, diabetes, or excess alcohol consumption. When fibrosis was seen, 1 or more comorbid factors almost always were present. Thus, phlebotomy therapy is warranted and cascade screening of relatives should be performed because expressing C282Y homozygotes may be detected.

Pharmacokinetic and Safety Study of Doxorubicin-eluting Beads in a Porcine Model of Hepatic Arterial Embolization

To present the pathologic and pharmacokinetic findings from hepatic embolization in a porcine model comparing doxorubicin-eluting beads with bland embolization and to correlate these findings with in vitro release kinetics. Drug-eluting beads (DEB; 100-300 microm and 700-900 microm) loaded with 37.5 mg doxorubicin per milliliter hydrated beads were used to embolize the hepatic artery feeding the left lobe of the liver in young adult Yucatan pigs (n = 5 per group). Control animals underwent embolization with bland beads (100-300 microm; n = 5). Systemic plasma levels of doxorubicin were measured and correlated to in vitro drug release. Blood sampling and histopathologic examination were performed during the 90-day follow-up. All animals underwent successful embolization, and the treatment was well tolerated. Mean volumes of beads administered were 2.0-3.4 mL, with mean doses of 127.5 mg and 78.7 mg of doxorubicin for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively. Gross pathologic examination revealed no effects on organs other than the liver. There was a transient increase in liver enzyme levels, particularly in the groups of animals who underwent embolization with 100- to 300-microm DEB. Histopathologic study showed mostly nonnecrotic changes with bland beads, whereas the effects of DEB were more severe, with large areas of pannecrosis evident with the 100- to 300-microm DEB. Maximum plasma concentrations were 651 ng/mL and 42.8 ng/mL for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively, observed at 1 minute for both groups. Correlation with in vitro data showed a strong linear relationship. Hepatic arterial embolization with DEB was shown to be safe and well tolerated. The locoregional delivery of doxorubicin from DEB caused targeted tissue damage with minimal systemic impact and could be a promising new approach to transarterial chemoembolization of solid tumors.

Steroid-Responsive Encephalopathy Associated With Autoimmune Thyroiditis

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), often termed Hashimoto encephalopathy, is a poorly understood and often misdiagnosed entity. To characterize the clinical, laboratory, and radiologic findings in patients with SREAT to potentially improve recognition of this treatable entity. Retrospective analysis of clinical features and diagnostic test data. Two affiliated tertiary care referral institutions. Twenty consecutive (6 male) patients diagnosed as having SREAT from 1995 to 2003. Clinical features and ancillary test findings associated with SREAT. The median age at disease onset was 56 years (range, 27-84 years). The most frequent clinical features were tremor in 16 (80%), transient aphasia in 16 (80%), myoclonus in 13 (65%), gait ataxia in 13 (65%), seizures in 12 (60%), and sleep abnormalities in 11 (55%). All patients were assigned an alternative misdiagnosis at presentation, most commonly viral encephalitis (n = 5), Creutzfeldt-Jakob disease (n = 3), or a degenerative dementia (n = 4). The most frequent laboratory abnormalities were increased liver enzyme levels in 11, increased serum sensitive thyroid-stimulating hormone levels in 11, and increased erythrocyte sedimentation rate in 5. In only 5 patients (25%) did cerebrospinal fluid abnormalities suggest an inflammatory process. Magnetic resonance imaging abnormalities believed to be related to the encephalopathy were present in 5 patients (26%). The clinical, laboratory, and radiologic findings associated with SREAT are more varied than previously reported. Misdiagnosis at presentation is common. This treatable syndrome should be considered even if the serum sensitive thyroid-stimulating hormone level and erythrocyte sedimentation rate are normal, the cerebrospinal fluid profile does not suggest an inflammatory process, and neuroimaging results are normal. Until the pathophysiologic mechanism of this and other autoimmune encephalopathies is better characterized, we believe that descriptive terms that reflect an association rather than causation are most appropriate for this syndrome.