PD-L1 Expression in Normal Endocrine Tissues Is Not Increased Despite High Incidence of PD-1 Inhibitor-Associated Endocrinopathies

ObjectiveTreatment with immune-checkpoint inhibitors often results in endocrine immune-related adverse events (irAEs), affecting the pituitary, thyroid, adrenal, and parathyroid glands and pancreas. The mechanism underlying the endocrine irAEs has not been fully elucidated, and it remains unclear why endocrine organs are so commonly affected. In the present study, we evaluated immunostaining patterns of programmed death-ligand 1 (PD-L1) in normal endocrine tissues to determine whether increased expression may explain the predilection of endocrinopathies in patients treated with programmed cell death-1 inhibitors.MethodsNormal formalin-fixed paraffin-embedded endocrine tissues (pituitary, thyroid, adrenal, pancreas, and parathyroid) were collected from our hospital’s pathology tissue archive. The tissues were assessed for membranous and cytoplasmic PD-L1 immunostaining using the Dako 22C3 pharmDx assay on an automated staining platform.ResultsWe examined 49 endocrine tissues, including 12 thyroid, 5 pancreatic, 17 adrenal, 5 parathyroid, and 10 pituitary samples. Samples with less than 1% membranous PD-L1–positive cells were considered negative, while those with more than 1% of PD-L1 membranous staining were considered positive. Immunostaining result of immune-related cells was also evaluated, considering the cytoplasmic PD-L1–positive cells with the same cutoff of 1%. None of the endocrine tissues demonstrated PD-L1 positivity higher than 1% in the relevant cells.ConclusionWhile our results do not suggest a role of PD-L1 expression in the pathogenesis of endocrine irAEs, they may serve as a basis for future studies further investigating the mechanisms of autoimmune, inflammatory, or malignant endocrine conditions.     

Granulomatous Adenohypophysitis after Interferon and Ribavirin Therapy

ObjectiveTo describe a case of granulomatous hypophysitis occurring after treatment with interferon alfa-2b and ribavirin for hepatitis C.MethodsClinical, radiologic, laboratory, and pathologic assessments of a woman with granulomatous hypophysitis and interferon-induced thyroiditis are presented.ResultsA 42-year-old woman with hepatitis C was treated with interferon alfa-2b and ribavirin for 5 months. She was referred after symptoms of thyrotoxicosis developed, in conjunction with laboratory and radiographic evidence of thyroiditis. During the initial evaluation, she was weak and hypotensive; biochemical evaluation showed undetectable plasma cortisol and corticotropin concentrations. Magnetic resonance imaging revealed diffuse enlargement of the pituitary gland, which encroached on but did not compress the optic chiasm. Treatment with supraphysiologic doses of prednisone resulted in clinical and radiographic improvement. Once physiologic doses of glucocorticoids were instituted, however, follow-up magnetic resonance imaging showed substantial progression of the diffuse pituitary enlargement and mild compression of the optic chiasm. Surgical debulking of the mass and histologic evaluation showed chronic, noncaseating gran-ulomatous hypophysitis. An extensive evaluation for secondary causes of granulomatous inflammation of the pituitary revealed only an elevated angiotensin-converting enzyme level; no organisms were identified. After 2 courses of high-dose glucocorticoids, she had radiographic evidence of decreased size of the pituitary lesion but continued to have multiple anterior pituitary hormone deficiencies.ConclusionGranulomatous hypophysitis and sarcoidosis of the pituitary are rare disorders. Hypophysitis should be considered in patients receiving interferon and ribavirin therapy who have symptoms consistent with pituitary dysfunction. (Endocr Pract. 2007;13:169-175)     

Thyroid Function Outcomes after Pegylated Interferon-α and Ribavirin Therapy - For Chronic Hepatitis C

ObjectiveTo assess the frequency of new thyroid disease, in patients who did not develop thyroid disease during treatment with interferon-a in combination with ribavirin for hepatitis C, during the 6-month period after the end of therapy.MethodsA prospective study was performed in 190 patients who underwent a combination of interferon-a and ribavirin therapy for hepatitis C infection during the 36-month period between 2006 and 2008. Thyroid function tests were performed at the completion of treatment and at 4, 12, and 24 weeks of follow-up.ResultsDuring the 6 months after the completion of interferon-a and ribavirin therapy in the 190 study patients with hepatitis C infection, there were 2 cases of thyroid disease. One patient had the typical biphasic thyroiditis, and the other had primary hypothyroidism. Thus, the prevalence of thyroid disease in this setting was 2 of 190 patients (1.0%).ConclusionThe majority (99%) of patients had normal thyroid outcomes at 6-month follow-up. Only 1 patient had symptoms. This finding is reassuring and eliminates the need for ongoing thyroid surveillance during this time and probably longer. In the absence of symptoms, only a single thyroid-stimulating hormone measurement at 6-month review is recommended. (Endocr Pract. 2010;16:934-939)     

Interferon-Induced Hypothyroidism Causing Reversible Pituitary Enlargement

ObjectiveTo present the first reported case of interferon-induced hypothyroidism with radiographic confirmation of secondary pituitary hyperplasia.MethodsWe describe the case of a woman with recurrent malignant melanoma, outline the details of her endocrine work-up, and illustrate the serial findings on magnetic resonance imaging of the head.ResultsA 26-year-old woman underwent surgical excision of a melanoma of the left thigh and 10 years later had a second melanoma removed from her right knee. Metastatic work-up revealed evidence of tumor involvement in the cervical and mediastinal lymph nodes. After treatment with interferon for 1 year, persistent fatigue and menstrual irregularities led to the laboratory diagnosis of hypothyroidism, and magnetic resonance imaging revealed pituitary enlargement. Both her endocrinopathy and the pituitary hyperplasia resolved with discontinuation of the interferon treatment and with institution of thyroid replacement therapy.ConclusionClinicians should be aware of the potential adverse effects of interferon therapy to avoid inappropriate diagnosis of a pituitary adenoma or metastatic lesion in patients with cancer who are treated with interferon. In addition, screening for hypothyroidism should be performed in patients receiving interferon. (Endocr Pract. 2008;14:219-223)     

慢性乙型肝炎病毒感染对妊娠期糖尿病及妊娠结局的影响

目的:探讨慢性乙型肝炎病毒(HBV)感染对妊娠期糖尿病(GDM)及妊娠结局的影响,为妊娠期产妇慢性HBV感染预防提供参考。方法:回顾性分析2015年2月-2017年2月在我院住院分娩的2615例慢性HBV感染产妇的临床病历资料,根据《慢性乙型肝炎防治指南》(2015年版)诊断标准,将所有产妇分为4组:慢性HBV携带者(A组)1128例、乙型肝炎e抗原(HBe Ag)阳性慢性乙型肝炎(B组)406例、HBe Ag阴性慢性乙型肝炎(C组)307例、非活动性乙型肝炎表面抗原(HBs Ag)携带者(D组)774例,并收集同期入院的823例HBV阴性产妇为对照组(E组)。比较各组的GDM发生率及不良妊娠结局发生率。结果:2615例慢性HBV感染产妇中,共发生GDM 866例,发生率为33.12%。B组与C组GDM发生率分别为38.92%、37.46%,均大于E组的30.74%(P0.05)。A组、B组、C组的妊娠期高血压疾病(PIH)发生率分别为7.98%、8.87%、9.77%,均高于E组的3.52%(P0.05);A组、B组、C组及早产发生率分别为3.10%、3.94%、4.56%,均高于E组的0.49%(P0.05)。C组的新生儿窒息发生率为1.63%,高于E组的0.36%(P0.05)。结论:产妇慢性HBV感染若合并肝功能受损或肝组织学病变,可能增加GDM的发生率,若HBV病毒复制活跃,可能导致PIH及早产发生风险增加。     

Endocrine Involvement in Systemic Amyloidosis

ObjectiveTo present an overview of the published data on endocrine involvement and endocrine dysfunction in patients with systemic amyloidosis.MethodsWe conducted a review of the medical literature using MEDLINE data sources, including clinical trials, in vitro studies, and case reports on pituitary, thyroid, parathyroid, pancreatic, adrenal, and gonadal involvement in systemic amyloidosis.ResultsReports of endocrine involvement in systemic amyloidosis seem to consist primarily of small-samplesize clinical trials or case reports, probably because of the rarity of the disease itself. Systemic amyloidosis mainly involves and causes functional impairment in the thyroid and testes in the endocrine system. Evaluation of adrenal function necessitates special consideration because amyloid infiltration of the adrenal glands resulting in failure may be a life-threatening condition. Amyloid deposition commonly seen in the pituitary gland and the pancreas of patients with Alzheimer disease and type 2 diabetes mellitus, respectively, is generally classified as local amyloidosis and should not be confused with systemic involvement. Additionally, detection of amyloid deposition in the thyroid and testes may have a diagnostic role in patients with suspected systemic or renal amyloidosis.ConclusionPublished data suggest that systemic amyloidosis frequently involves the endocrine system, and endocrine dysfunction seems to be not as rare as previously thought. A rapidly growing goiter or symptoms and signs of adrenal or gonadal dysfunction should raise suspicion of amyloid infiltration. Involvement of pituitary, parathyroid, and pancreatic sites in systemic amyloidosis still remains to be clarified. Further studies with larger sample sizes are needed for complete characterization of the effect of systemic amyloidosis on the endocrine system. (Endocr Pract. 2010;16:1056-1063)     

Thyroid Disease in Chronic Hepatitis C Infection Treated With Combination Interferon-a and Ribavirin: Management Strategies and Future Perspective

ObjectiveHepatitis C virus (HCV) infection is one of the major epidemics afflicting young people in both developed and developing countries. The most common endocrine disorder associated with this infection, especially in conjunction with interferon-α (IFN-α)-based therapy, is thyroid disease (TD). This review examines the development of TD before, during, and after the completion of treatment with combination IFN-α and ribavirin (RBV) for chronic HCV infection. We also summarize the current understanding of the natural history of the condition and propose management and follow-up guidelines.MethodsPubMed was searched up to June 30, 2011 for English-language publications that contained the search terms “hepatitis C virus,” “chronic hepatitis C,” “HCV,” “thyroid disease,” “thyroiditis,” “autoimmunity,” “inter-feron-alpha,” and “ribavirin.” Additional publications were identified from the reference lists of identified papers. The included studies were original research publications and included combination IFN-α and RBV use in patients that developed TD.ResultsThe prevalence of TD before combination IFN-α and RBV therapy ranges from 4.6 to 21.3%; during therapy, 1.1 to 21.3%; and after therapy, 6.7 to 21.3%. The most common TD is thyroiditis. Thyroid function testing (TFT) frequency and diagnostic criteria for various thyroid conditions are not standardized, and many of the existing studies are retrospective.ConclusionPatients undergoing this therapy should be assessed with a standardized protocol to appropriately detect and manage developed TD. Based on the currently available literature, we recommend that patients receiving combination interferon-α and RBV therapy undergo monthly thyrotropin (TSH) level testing. (Endocr Pract. 2013;19:292-300)     

Silent Thyroiditis,Isolated Corticotropin Deficiency,and Alopecia Universalis in a Patient With Ulcerative Colitis and Elevated Levels of Plasma Factor VIII: An Unusual Case of Autoimmune Polyglandular Syndrome Type 3

ObjectiveTo describe an unusual case of autoimmune polyglandular syndrome (APS) type 3 and provide a brief review of the literature.MethodsWe present the clinical course and laboratory data of a patient with silent thyroiditis, isolated corticotropin (adrenocorticotropic hormone or ACTH) deficiency, alopecia universalis, and ulcerative colitis with an associated hypercoagulable state. The related literature is also reviewed briefly.ResultsA 43-year-old man who had a history of ulcerative colitis with an associated hypercoagulable state and alopecia universalis was referred to the endocrinology department for evaluation of fatigue and a mildly elevated level of thyrotropin (thyroid-stimulating hormone or TSH). He previously had mildly increased TSH levels, for which low-dose levothyroxine therapy had been prescribed. During use of this therapy, a suppressed TSH level developed, necessitating discontinuation of thyroid hormone therapy; a subsequent increase in TSH value was followed by a spontaneous return to euthyroidism. An ACTH stimulation test revealed adrenal insufficiency. His ACTH level was low, 21-hydroxylase antibodies were not present, and further testing demonstrated otherwise intact pituitary function. Magnetic resonance imaging of his pituitary gland showed normal findings. Treatment with hydrocortisone promptly decreased his fatigue. He was found to have an elevated factor VIII level as the cause of his hypercoagulable state. The patient continues to feel well with use of hydrocortisone therapy and has normal thyroid function.ConclusionThis patient’s components of APS type 3 have not been previously reported; thus, the complex nature of the APS variants is supported. (Endocr Pract. 2009;15:138-142)     

The Multifaceted Associations of Hepatobiliary Disease and Diabetes

ObjectiveTo investigate the association of diabetes and hepatobiliary disease.MethodsWe performed a MEDLINE search of the English-language literature published between January 1980 and January 2007 for studies in which diabetes was associated with liver diseases.ResultsThrough its association with the insulin resistance syndrome, type 2 diabetes is associated with nonalcoholic fatty liver disease, nonalcoholic steatohepatitis (NASH), NASH-cirrhosis, and NASH-cirrhosis-related hepatocellular carcinoma. Because of the association with insulin resistance, insulin sensitizers may slow or even arrest the progress of these diseases. Type 2 but not type 1 diabetes is associated with hepatitis C virus but not hepatitis B viral infection. This association is likely due to hepatitis C viral infection of the pancreatic β-cells. Early detection and antiviral therapy can decelerate the development of diabetes. Type 1 diabetes is associated with hemochromatosis and autoimmune hepatitis. Because of the presence of autonomic neuropathy, cholelithiasis but not cholecystitis is more common in patients with diabetes than in the general population. Therefore, asymptomatic cholelithiasis in patients with diabetes no longer warrants a cholecystectomy. In patients with advanced liver disease of any cause, insulin resistance and diabetes have an increased frequency of occurrence and can be reversed with liver transplantation. Rarely, medications used to treat type 2 diabetes have been associated with drug-induced hepatitis.ConclusionThe prevalence of hepatobiliary diseases is increased in patients with diabetes. Early recognition and treatment of these conditions can prevent, stabilize, or even reverse hepatic damage and prevent the development of hepatic carcinoma and liver failure. (Endocr Pract. 2007;13:300-312)     

Autoimmune Hyperthyroidism due to Secondary Adrenal Insufficiency: Resolution with Glucocorticoids

ObjectiveTo describe the course of autoimmune hyperthyroid disease in a patient with corticotropin (ACTH) deficiency treated with glucocorticoids.MethodsWe report the clinical presentation, laboratory data, imaging studies, and management of a patient with weight loss, fatigue, apathy, hallucinations, and arthritis.ResultsAutoimmune hyperthyroidism (positive thyroperoxidase and thyroglobulin antibodies and borderline positive thyrotropin receptor antibody) was diagnosed in a 71-year-old woman. New psychotic symptoms prompted brain magnetic resonance imaging, which revealed a partially empty sella. Undetectable morning cortisol, undetectable ACTH, and failure to stimulate cortisol with synthetic ACTH (cosyntropin 250 mcg) secured the diagnosis of long-standing secondary adrenal insufficiency. Hydrocortisone replacement improved the patient’s symptoms, resolved the thyroid disease, and decreased thyroid antibody titers. In retrospect, the patient recalled severe postpartum hemorrhage requiring blood transfusion at age 38 years. A Sheehan event probably occurred 33 years before the patient presented with corticotropin deficiency. Hyperthyroidism accelerated cortisol metabolism and provoked symptoms of adrenal insufficiency.ConclusionsThe hypocortisolemic state may precipitate hyperimmunity and autoimmune thyroid disease. Rapid resolution of hyperthyroidism and decreased thyroid antibody titers with glucocorticoid treatment support this hypothesis. (Endocr Pract. 2011;17:85-90)     

Association of ipilimumab therapy for advanced melanoma with secondary adrenal insufficiency: a case series

ObjectiveTo present a case series of ipilimumabrelated secondary adrenal insufficiency.MethodsIn this cases series, we review the presentation, evaluation, diagnosis, and management of patients with advanced melanoma who received ipilimumab and were referred to our endocrinology clinic for evaluation of hormonal abnormalities.ResultsSeven patients presented with symptoms, signs, or biochemical evidence of adrenal insufficiency 6 to 12 weeks after starting ipilimumab therapy. Ipilimumab is a cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody that is approved for the treatment of metastatic melanoma and has widespread use for this disease. All 7 patients had biochemical evidence of profound secondary adrenal insufficiency. Thyroid function abnormalities, central hypogonadism, and low insulinlike growth factor 1 levels were seen in a subset of patients. Only 2 patients had abnormal findings on pituitary magnetic resonance imaging. Posterior pituitary function remained normal.ConclusionsOur findings suggest that the enhanced immune response associated with ipilimumab therapy may have a predilection for corticotroph and possibly thyrotroph cells. We recommend periodic hypothalamic-pituitary-adrenal axis monitoring for patients on this therapy.(Endocr Pract. 2012;18:351-355)     

Multiple Disease Associations in Autoimmune Polyglandular Syndrome Type II

ObjectiveAutoimmune polyglandular syndrome type II (APS II) is characterized by adrenal insufficiency (Addison’s disease), autoimmune thyroid disease, and/or type 1 diabetes mellitus (DM1). Multiple other autoimmune diseases have been associated with APS II. Here we report a case of a patient with APS II who over the course of 10 years developed Addison’s disease, hypothyroidism, DM1, Hashimoto’s encephalopathy, vitiligo, celiac disease, seronegative arthritis, and ulcerative colitis. This is a particularly aggressive course of APS II, and this combination of autoimmune diseases has not been previously reported.MethodsA 25-year-old female with a history of ulcerative colitis (UC), celiac disease, and DM1 presented to our institution with mental status changes. She was diagnosed with Hashimoto’s encephalopathy and treated with high-dose steroids and intravenous immunoglobulin (IVIG). She recovered well from her encephalopathy but her posthospitalization course was complicated due to the development of Addison’s disease, vitiligo, seronegative arthritis, and hypothyroidism.ResultsThe current understanding of APS II and its autoimmune disease associations are briefly summarized.Submitted for publication April 10, 2014 Accepted for publication July 10, 2014 The association of UC and Hashimoto’s encephalopathy with APS II is novel and discussed in detail.ConclusionA case of a patient with APS II with a dramatic development of 8 autoimmune diseases over 10 years is described. The novel APS II developments of Hashimoto’s encephalopathy and UC are discussed. This case highlights the potential complexity and severity of the clinical course of APS II. (Endocr Pract. 2014;20:e250-e255)     

Thyroid disease is a favorable prognostic factor in achieving sustained virologic response in chronic hepatitis C undergoing combination therapy: A nested case control study

Background

Interferon-α in combination with ribavirin is the current gold standard for treatment of chronic hepatitis C. It is unknown if the development of autoimmune thyroid disease (TD) during treatment confers an improved chance of achieving sustained virologic response. The aim of this study is to assess the chance of achieving sustained virologic response (SVR) in patients who developed TD during treatment when compared with those who did not.

Methods

We performed a tertiary hospital-based retrospective nested case-control analysis of 19 patients treated for hepatitis C who developed thyroid disease, and 76 controls (matched for age, weight, gender, cirrhosis and aminotransferase levels) who did not develop TD during treatment. Multivariate logistic-regression models were used to compare cases and controls.

Results

The development of TD was associated with a high likelihood of achieving SVR (odds ratio, 6.0; 95% confidence interval, 1.5 to 24.6) for the pooled group containing all genotypes. The likelihood of achieving SVR was increased in individuals with genotype 1 HCV infection who developed TD (odds ratio, 5.2; 95% confidence interval, 1.2 to 22.3), and all genotype 3 patients who developed TD achieved SVR.

Conclusions

Development of TD during treatment for hepatitis C infection is associated with a significantly increased chance of achieving SVR. The pathophysiogical mechanisms for this observation remain to be determined.

Trial Registration

The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRB12610000830099     

Coenzyme Q10 evaluation in pituitary-adrenal axis disease: preliminary data

In previous works we have demonstrated plasma CoQ10 alterations in pituitary diseases, such as acromegaly or secondary hypothyroidism. However, pituitary lesions can induce complex clinical pictures due to alterations of different endocrine axes controlled by pituitary itself. A further rationale for studying CoQ10 in pituitary-adrenal diseases is related to the common biosynthetic pathway of cholesterol and ubiquinone. We have therefore assayed plasma CoQ10 levels in different conditions with increased or defective activity of pituitary-adrenal axis (3 subjects with ACTH-dependent adrenal hyperplasia, 2 cases of Cushing's disease and 1 case of 17-alpha-hydroxylase deficiency; 10 subjects with secondary hypoadrenalism, including three subjects with also secondary hypothyroidism). CoQ10 levels were significantly lower in isolated hypoadrenalism than in patients with adrenal hyperplasia and multiple pituitary deficiencies (mean +/- SEM: 0.57 +/- 0.04 vs 1.08 +/- 0.08 and 1.10 +/- 0.11 microg/ml, respectively); when corrected for cholesterol levels, the same trend was observed, but did not reach statistical significance. These preliminary data indicate that secretion of adrenal hormones is in some way related to CoQ10 levels, both in augmented and reduced conditions. However, since thyroid hormones have an important role in modulating CoQ10 levels and metabolism, when coexistent, thyroid deficiency seems to play a prevalent role in comparison with adrenal deficiency.     

Autoimmune Thyroid Disease in the Use of Alemtuzumab for Multiple Sclerosis: A Review

ObjectiveThe monoclonal antibody alemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in multiple sclerosis (MS) patients when compared to β-interferon. The development of autoimmune diseases, including thyroid disease, has been reported in the literature with a frequency of 20 to 30%. In this article, we describe 4 cases of alemtuzumab-induced thyroid disease in patients with MS. We also performed a systematic review of the available literature.MethodsFour patients who had received alemtuzumab for MS and subsequently developed thyroid dysfunction are presented. We compared our patients' clinical courses and outcomes to established disease patterns. We also undertook a systematic review of the published literature.ResultsAll 4 patients presented with initial hyperthyroidism associated with elevated thyroid-stimulating hormone (TSH) receptor antibodies (TRAb). In 2 cases, hyperthyroidism did not remit after a total of 24 months of carbimazole therapy, and they subsequently underwent subtotal thyroidectomy. The third case subsequently developed biochemical hypothyroidism and required thyroxine replacement, despite having a markedly raised initial TRAb titer. Autoimmunity following alemtuzumab therapy in MS appears to occur as part of an immune reconstitution syndrome and is more likely in smokers who have a family history of autoimmune disease.ConclusionManagement of alemtuzumab-induced thyroid disease is similar to the management of “wild-type” Graves’ disease. The use of alemtuzumab in this setting will necessitate close monitoring of thyroid function and early intervention when abnormalities are developing. (Endocr Pract. 2013;19:821-828)     

A Case of Nonischemic Cardiomyopathy Associated with Autoimmune Polyglandular Syndrome Type III

Objective:To report a case of nonischemic dilated cardiomyopathy associated with autoimmune polyglandular syndrome (APS) type III.MethodsA review of our patient’s medical records was undertaken, and her clinical history, investigations, and outcome are described. In addition, a literature review of nonischemic dilated cardiomyopathy occurring in association with autoimmune polyendocrinopathies was performed.ResultsAPS is diagnosed once a patient has developed at least 2 organ specific autoimmune diseases. APS III involves a combination of autoimmune diabetes and Graves’ disease without adrenal insufficiency. Autoimmune cardiomyopathies are not described as a feature of this condition; however, there are a few reported cases of patients with autoimmune polyendocrinopathies developing a nonischemic dilated cardiomyopathy. In this case, a 30-year-old female developed vitiligo, Graves’ disease, and latent autoimmune diabetes of the adult (LADA) over a 5-year period before presenting with conscious ventricular tachycardia (VT). This evolved into acute severe biventricular failure within a few weeks, which failed to resolve after adequate treatment of her other autoimmune conditions.ConclusionAlthough nonischemic cardiomyopathies have been associated with APS in a few published cases, this is the first case to our knowledge in a patient with APS III. (Endocr Pract. 2014;20:e183-e186)     

Seroprevalence of the Hepatitis B,Hepatitis C,and Human Immunodeficiency Viruses and Treponema pallidum at the Beijing General Hospital from 2010 to 2014: A Cross-Sectional Study

BackgroundThe hepatitis B, hepatitis C, human immunodeficiency viruses and Treponema pallidum are important causes of infectious diseases concern to public health.MethodsBetween 2010 and 2014, we used an automated chemiluminescence microparticle immunoassay to detect the hepatitis B, hepatitis C, and human immunodeficiency viruses as well as Treponema pallidum (the rapid plasma regain test was used in 2010–2011). Positive human immunodeficiency virus tests were confirmed via western blotting.ResultsAmong 416,130 subjects, the seroprevalences for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum were 5.72%, 1.23%, 0.196%, and 0.76%, respectively. Among 671 patients with positive human immunodeficiency virus results, 392 cases were confirmed via western blotting. Hepatitis B and human immunodeficiency virus infections were more frequent in men (7.78% and 0.26%, respectively) than in women (4.45% and 0.021%, respectively). The hepatitis B and C virus seroprevalences decreased from 6.21% and 1.58%, respectively, in 2010, to 5.37% and 0.988%, respectively, in 2014. The human immunodeficiency virus seroprevalence increased from 0.04% in 2010 to 0.17% in 2014, and was elevated in the Infectious Disease (2.65%), Emergency (1.71%), and Dermatology and Sexually Transmitted Diseases (1.12%) departments. The specificity of the human immunodeficiency virus screening was 71.4%. The false positive rates for the Treponema pallidum screening tests increased in patients who were 60–70 years old. The co-infection rates for the hepatitis C and human immunodeficiency viruses were 0.47% in hepatitis C virus-positive patients and 7.33% in human immunodeficiency virus-positive patients.ConclusionsDuring 2010–2014, hepatitis B virus and human immunodeficiency virus infections were more frequent among men at our institution. Although the seroprevalences of hepatitis B and C viruses decreased, the seroprevalence of human immunodeficiency virus infection increased (with higher seroprevalences in high-risk departments). Older patients were more likely to exhibit false positive findings for syphilis.     

Fungal Thyroiditis: An Overview

The authors review the epidemiology, clinical manifestations, diagnosis, and treatment of fungal thyroiditis cases previously reported in the medical literature. Aspergillus was by far the most common cause of fungal thyroiditis. Immunocompromised patients, such as those with leukemia, lymphoma, autoimmune diseases, and organ-transplant patients on pharmacological immunosuppression were particularly at risk. Fungal thyroiditis was diagnosed at autopsy as part of disseminated infection in a substantial number of patients without clinical manifestations and laboratory evidence of thyroid dysfunction. Local signs and symptoms of infection were indistinguishable from other infectious thyroiditis and included fever, anterior cervical pain, thyroid enlargement sometimes associated with dysphagia and dysphonia, and clinical and laboratory features of transient hyperthyroidism due to the release of thyroid hormone from follicular cell damage, followed by residual hypothyroidism. Antemortem diagnosis of fungal thyroiditis was made by direct microscopy and culture of a fine-needle aspirate, or/and biopsy in most cases. Since most patients with fungal thyroiditis had disseminated fungal infection with delay in diagnosis and treatment, the overall mortality was high.     

Chronic Hepatitis C Virus Infection Is Associated with the Development of Rheumatoid Arthritis: A Nationwide Population-Based Study in Taiwan

ObjectiveThe association between chronic hepatitis virus infection and rheumatoid arthritis (RA) remains debatable. This nationwide population-based cohort study assessed the risk of RA among patients with a chronic infection of hepatitis B and/or C virus.ResultsAfter adjusting for covariates, chronic HCV infection alone was significantly associated with an increased risk for RA (hazard ratio (HR)  = 2.03, 95% confidence interval (CI)  = 1.27–3.22). The increased risk for RA among participants with chronic HCV infection remained significant after restricting the analysis to those who were prescribed disease-modifying anti-rheumatic drugs. The corresponding HR for the overall sample was 1.89 (95% CI  = 1.15–3.11). However, HBV carriers did not appear to be at a significantly higher risk for RA.ConclusionOur data imply that chronic HCV infection is associated with RA development.     

The Absence of Thyroid Disease in an Australian Hepatitis C Cohort Treated With Triple Combination Therapy: A Paradigm Shift

Objective: To assess the prevalence of thyroid disease in triple combination therapy with interferon (IFN)-α, ribavirin (RBV), and protease inhibitors (boceprevir and telaprevir) for the treatment of chronic hepatitis C virus (HCV) infection in an Australian hepatitis C cohort. Also, to compare with those who received dual RBV and IFN in the past.Methods: A preliminary, retrospective, and nested case control study of thyroid disease in patients who underwent triple combination therapy for chronic HCV infection compared with dual therapy at a major tertiary referral hospital center. Fifty-nine patients were treated with such therapy at the Hunter New England Area Hepatitis C Treatment Center. Of these, 38 were treated with boceprevir and 21 with telaprevir. All had genotype 1 HCV infection. The main outcome measures included (1) the prevalence of thyroid disease (TD), including hyperthyroidism and hypothyroidism, and (2) thyroid outcome comparison with patients who had received dual therapy.Results: There was no case of TD detected for the entire duration of therapy with triple anti-HCV therapy. There was a significant absence of TD in the protease inhibitor–treated group.Conclusion: No case of TD was detected during the treatment of HCV patients with protease inhibitor–based triple therapy. The reasons for this are unclear. Larger studies are necessary to confirm this finding.Abbreviations: CV = coefficient of variation fT₃ = free triiodothyronine fT₄ = free thyroxine HCV = hepatitis C virus IFN-α = interferon-alpha PI = protease inhibitor RBV = ribavirin TD = thyroid disease TSH = thyroid-stimulating hormone TTX = thyrotoxicosis