Thyroid dysfunction during treatment of chronic hepatitis C with interferon alpha: no association with either interferon dosage or efficacy of therapy

OBJECTIVES: Treatment of chronic hepatitis C with interferon-alpha (IFN-alpha) may induce thyroid disorders. We evaluated whether this risk is related to the dosage of IFN-alpha or the virological treatment response. Other possible risk factors as well as the evolution of the thyroid abnormalities were also studied. METHODS: In this prospective trial (n=254), thyroid-stimulating hormone (TSH), free thyroxin (fT4) and thyroid peroxidase autoantibodies were measured before, during and after treatment for hepatitis C virus (HCV). The patients were randomized to either induction therapy [IFN-alpha 6 million units (MIU) daily for 4 weeks and 3 MIU 3/7 days for 22 weeks] or conventional therapy [IFN-alpha 3 MIU 3/7 days for 26 weeks]. In addition, all patients received ribavirin (1000 or 1200 mg) daily. Sustained virological response was defined as loss of detectable HCV RNA at 6 months follow-up. Thyroid dysfunction was defined as TSH level below or above the normal range (0.2-4.5 MIU L-1). RESULTS: Biochemical thyroid dysfunction developed in 30 (11.8%) of 254 patients. Hypothyroidism (TSH > 4.5 MIU L-1) was seen in 20 and hyperthyroidism (TSH < 0.2 MIU L-1) in 10 patients. Nine of the 30 patients developed symptomatic thyroid disease and HCV treatment was discontinued because of thyroid dysfunction in three of these patients. Thyroid dysfunction occurred in 15 (11.7%) of 128 patients who received high-dose IFN-alpha induction therapy as compared with 15 (11.9%) of 126 patients who received conventional IFN-alpha therapy (P=0.96). Amongst 231 patients who completed all 6 months of HCV treatment, a sustained virological response was obtained in 19 (66%) of 29 with thyroid dysfunction and 109 (54%) of 202 without (P=0.24). By multivariate analysis female gender and Asian origin were independent predictors of developing biochemical thyroid dysfunction (P < 0.01). CONCLUSION: Thyroid dysfunction occurred in 11.8% of patients treated for chronic hepatitis C with IFN-alpha and ribavirin. Neither the IFN-alpha dosage nor the virological response to treatment were related to the incidence of thyroid dysfunction.     

抗丙型肝炎病毒治疗过程中甲状腺功能异常与病毒学应答关系研究*

目的探讨聚乙二醇干扰素（Peg-IFN）联合利巴韦林（RBV）治疗慢性丙型肝炎患者发生甲状腺功能异常的转归及其对抗病毒疗效的影响。方法204例（HCV基因1b型感染173例,2a型9例,3b型2例,未分型20例）慢性丙型肝炎患者应用Peg-IFN联合RBV抗病毒治疗。对于基因1型和未分型者治疗48 w,对于基因2型和3型治疗24 w。采用化学发光免疫分析法检测血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、超敏促甲状腺激素（sTSH）;采用间接免疫荧光法检测血清抗甲状腺球蛋白抗体（Tg-Ab）、抗甲状腺过氧化物酶抗体（TPOAb）、抗促甲状腺激素受体抗体（TRAb）、抗甲状腺微粒体抗体。结果在治疗过程中,发生甲状腺功能异常43例（19.0%）,其中甲状腺功能减退症7例（16.3%）,亚临床甲状腺功能减退症17例（39.5%）,甲状腺功能亢进症11例（25.6%）,亚临床甲状腺功能亢进症8例（18.6%）;甲状腺功能异常集中发生于治疗后24~36 w;在观察结束时,37例甲状腺功能异常患者自发或者经药物治疗后甲状腺功能恢复正常,6例患者仍需要密切监测甲状腺功能或服用抗甲状腺药物;43例甲状腺功能异常与161例无甲状腺功能异常患者RVR、EVR、ETVR、SVR、治疗结束后96 w病毒学应答率差异均无统计学意义（P>0.05）。结论Peg-IFN联合RBV治疗慢性丙型肝炎患者诱发甲状腺功能异常的发生率为19.0%,大部分是可逆的,甲状腺功能异常不影响抗病毒疗效。     

Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C

OBJECTIVE Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy. DESIGN Prospective study. PATIENTS A series of 68 patients with chronic hepatitis C completed a therapeutic trial of interferon alpha 2b (IFN), randomized for dose adaptation, lasting for 24 weeks. MEASUREMENTS TSH and autoantibodies against thyroid were looked for at (- 2) weeks and 24 weeks in all patients. Blood samples obtained at (-2), 12, and 24 weeks were stored for additional hormonal studies in patients who developed thyroid dysfunction. Such patients with thyroid dysfunction were followed up for at least one year. RESULTS Only one out of 68 patients had abnormal TSH levels, and two had thyroid autoantibodies prior to interferon therapy. Eight patients (12%) developed thyroid dysfunction (five hypothyroidism and three hyperthyroidism) during treatment. In four patients (all of them with thyroid dysfunction, P< 0-001) antimicrosomal, antithyro-globulin, and/or anti-TSH receptor antibodies appeared during interferon therapy. All patients recovered normal thyroid function within 15 years after interferon withdrawal. No pretreatment risk factor was identified. The patients with thyroid dysfunction did not significantly differ from the others as regards the dose of interferon they received or the rate of normalization of transaminases. CONCLUSION (i) A 12% incidence of thyroid dysfunction was observed under interferon therapy: (ii) secondary appearance under interferon therapy of elevated thyroid autoantibodies was a risk factor; (iii) the thyroid disorders induced by interferon were reversible.     

Prevalence of subclinical thyroid dysfunction and its relation to socioeconomic deprivation in the elderly: a community-based cross-sectional survey

CONTEXT: Population-based screening has been advocated for subclinical thyroid dysfunction in the elderly because the disorder is perceived to be common, and health benefits may be accrued by detection and treatment. OBJECTIVE: The objective of the study was to determine the prevalence of subclinical thyroid dysfunction and unidentified overt thyroid dysfunction in an elderly population. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional survey of a community sample of participants aged 65 yr and older registered with 20 family practices in the United Kingdom. EXCLUSIONS: Exclusions included current therapy for thyroid disease, thyroid surgery, or treatment within 12 months. OUTCOME MEASURE: Tests of thyroid function (TSH concentration and free T4 concentration in all, with measurement of free T3 in those with low TSH) were conducted. EXPLANATORY VARIABLES: These included all current medical diagnoses and drug therapies, age, gender, and socioeconomic deprivation (Index of Multiple Deprivation, 2004). ANALYSIS: Standardized prevalence rates were analyzed. Logistic regression modeling was used to determine factors associated with the presence of subclinical thyroid dysfunction. RESULTS: A total of 5960 attended for screening. Using biochemical definitions, 94.2% [95% confidence interval (CI) 93.8-94.6%] were euthyroid. Unidentified overt hyper- and hypothyroidism were uncommon (0.3, 0.4%, respectively). Subclinical hyperthyroidism and hypothyroidism were identified with similar frequency (2.1%, 95% CI 1.8-2.3%; 2.9%, 95% CI 2.6-3.1%, respectively). Subclinical thyroid dysfunction was more common in females (P < 0.001) and with increasing age (P < 0.001). After allowing for comorbidities, concurrent drug therapies, age, and gender, an association between subclinical hyperthyroidism and a composite measure of socioeconomic deprivation remained. CONCLUSIONS: Undiagnosed overt thyroid dysfunction is uncommon. The prevalence of subclinical thyroid dysfunction is 5%. We have, for the first time, identified an independent association between the prevalence of subclinical thyroid dysfunction and deprivation that cannot be explained solely by the greater burden of chronic disease and/or consequent drug therapies in the deprived population.     

干扰素治疗慢性丙型肝炎发生甲状腺功能异常的分析

目的：探讨干扰素治疗慢性丙型肝炎患者后发生甲状腺功能异常的情况及相关因素的分析。方法回顾性分析206例慢性丙型肝炎患者,观察89例干扰素治疗前和117例治疗后甲状腺功能的异常情况及其影响因素,Logistic分析发生甲状腺功能异常的危险因素。结果干扰素治疗前的89例患者中,有23例合并甲状腺功能异常,其中甲状腺功能减退症7例,甲状腺功能亢进症2例,亚临床甲状腺功能减退症14例;干扰素治疗后的117例患者中,有17例发生甲状腺功能异常,其中甲状腺功能减退4例,为桥本甲状腺炎2例和非自身免疫性甲状腺功能减退2例;甲状腺功能亢进1例;亚临床甲状腺功能减退症12例。多元Logistic回归分析显示,女性（OR＝5．828）、体内预存抗甲状腺自身抗体（OR＝35．393）是慢性丙型肝炎患者使用干扰素治疗后诱发甲状腺疾病的独立危险因素。结论干扰素治疗慢性丙型肝炎可导致甲状腺功能异常的发生;对体内预存大量抗甲状腺过氧化物酶抗体的女性,要监测甲状腺功能,定期复查。     

An Analysis of the Natural Course of Subclinical Hyperthyroidism

BackgroundOur aim was to evaluate the incidence rate of overt hyperthyroidism in a cohort of patients with subclinical hyperthyroidism and to assess the potential risk factors for the development of overt thyroid hyperfunction.MethodsWe performed a retrospective analysis in 75 patients (68 women, mean age 62.2 ± 14.2 years) with subclinical hyperthyroidism and different grades of serum thyrotropin (TSH) suppression. Incidence rate of overt hyperthyroidism and survival time, ie, time without requiring therapy for overt hyperthyroidism, were studied.ResultsThirty-four patients (45.3%) developed overt hyperthyroidism and 15 (20.0%) reverted to normal TSH values. The incidence rate of overt hyperthyroidism was 9.69 cases per 100 patient-year in the whole population and 4.12, 7.41, and 29.63 cases per 100 patient-year in subjects with initial TSH values of 0.30 to 0.49, 0.10 to 0.29, and <0.10 mU/L, respectively. Kaplan-Meier analysis of survival time curves showed that the development of overt thyroid hyperfunction was significantly related to the presence of symptoms of hyperthyroidism (P < 0.05) and low (<0.10 mU/L) TSH concentrations (P < 0.001). A stepwise multivariate Cox regression analysis showed that both symptoms and low TSH values were significant factors for progression to overt thyrotoxicosis.ConclusionsTSH concentration is the most powerful predictor in the outcome of patients with subclinical hyperthyroidism. Our results suggest that patients with values under 0.10 mU/L have the highest probability to develop overt thyroid hyperfunction. In patients with TSH values higher than this value, the risk of progression is notably lower.     

Incidence of postradioiodine immunogenic hyperthyroidism/Graves' disease in relation to a temporary increase in thyrotropin receptor antibodies after radioiodine therapy for autonomous thyroid disease.

BACKGROUND: The aim of the study was to analyze retrospectively the incidence of postradioiodine immunogenic hyperthyroidism/Graves' disease in relation to a temporary increase in TSH-receptor antibodies without overt hyperthyroidism after radioiodine therapy for autonomous thyroid disease. PATIENTS AND METHODS: Between May 2000 and May 2003 all patients (n = 1,357) who had undergone radioiodine therapy for autonomous thyroid disease were retrospectively analyzed for development of postradioiodine immunogenic hyperthyroidism. On pretreatment evaluation 565 of 1,357 patients (41.6%) had unifocal autonomous thyroid disease (UFA), 693 of 1,357 patients (51.1%) had multifocal autonomous thyroid disease (MFA), and 99 of 1,357 patients (7.3%) had diffuse thyroid disease (DISS). Free triiodothyronine (FT(3)), free thyroxine (FT(4)), thyrotropin (TSH), and thyroid antibodies were measured. Ultrasound examinations and thyroid scintigraphy were performed before and after radioiodine therapy. A sensitive assay with the human TSH receptor as antigen was chosen for measurement of the TSH receptor antibody and the study was limited to analysis of data obtained since introduction of this assay. RESULTS: Fifteen of 1,357 patients (1.1%) (UFA, 8/565 = 1.4%; MFA, 6/693 = 0.9%; DISS 1/99 = 1.0%) developed postradioiodine hyperthyroidism between 1 and 13 months after radioiodine therapy with clinically overt hyperthyroidism and an elevation of TSH receptor antibodies. Patients with elevated thyroid peroxidase (TPO) antibodies before radioiodine therapy had an almost 10-fold (6/57 patients =10.5%) higher risk of developing postradioiodine immunogenic hyperthyroidism. Thirteen of 999 patients (1.3%) with antibody measurements after radioiodine therapy (UFA, 2/421 = 0.5%; MFA, 9/494 = 1.8%, DISS, 2/84 = 2.4%) had increased levels of TSH receptor antibodies and, to some extent, TPO antibodies without development of clinically overt hyperthyroidism. CONCLUSIONS: There is an estimated 1.1% risk of developing postradioiodine immunogenic hyperthyroidism/Graves' disease in patients undergoing radioiodine therapy for autonomous thyroid disease and this increases approximately 10-fold when TPO antibody levels are elevated before radioiodine therapy. Furthermore, there is an estimated 1.3% risk of a temporary increase of TSH receptor antibodies after radioiodine therapy for autonomous thyroid disease without development of clinically overt hyperthyroidism.     

慢性丙型肝炎患者甲状腺功能异常情况观察

目的 了解慢性丙型肝炎患者甲状腺疾病发生情况及其与肝功能、病毒复制、肝硬化发生及合并症的关系.方法 检测133例未接受干扰素治疗的慢性丙型肝炎患者血清中总三碘甲状腺原氨酸、总甲状腺素、游离三碘甲状腺原氨酸、游离甲状腺素和促甲状腺激素(thyroid stimulating hormone,TSH),并收集患者临床资料,...     

Hepatitis C virus infection and thyroid diseases]

INTRODUCTION: The combination of hepatitis C virus (HCV) infection and thyroid diseases raises several issues that are the prevalence of thyroid autoimmunity in patients with chronic hepatitis C, the prevalence of HCV infection in patients with autoimmune thyroid diseases, and the effects of interferon alpha treatment on thyroid function in chronic HCV hepatitis. CURRENT KNOWLEDGE AND KEY POINTS: The prevalence of anti-thyroid auto-antibodies ranges from 4.6 to 15% in HCV infection, which is considered as significant by various authors. Results have to be interpreted according to the following: the type of auto-antibodies detected, the age, sex, ethnic origin of the population studied, and characteristics of the control population. Recent data are suggestive of a high prevalence of anti-thyroid auto-antibodies in females with HCV infection. An increased prevalence of HCV infection in patients with Hashimoto's thyroiditis is not confirmed. During treatment of chronic hepatitis C, interferon alpha induces thyroid dysfunctions (3 to 15% of the cases) with various clinical presentations. Hypothyroidism is more common (two out of three cases) than hyperthyroidism (one out of three cases). Hyperthyroidism followed by hypothyroidism has also been described. Clinical symptoms vary, ranging from subclinical to severe manifestations. Thyroid dysfunction may be delayed after discontinuation of the interferon treatment. Hypothyroidism is easily cured by L-thyroxine replacement therapy when necessary, and regression may be observed following discontinuation of interferon treatment. Each case of hyperthyroidism has to be precisely evaluated. Development of anti-thyroid antibodies or an increase in anti-thyroid antibodies titers is often observed during interferon alpha treatment, thus suggesting the existence of immunological mechanisms at the origin of thyroid dysfunction. Furthermore, interferon would directly act on iodine. FUTURE PROSPECTS AND PROJECTS: Clinical studies are still necessary to better clarify the links between HCV infection and thyroid autoimmunity, and to determine risk factors for the development of thyroid dysfunction during interferon alpha therapy. The effects of HCV and interferon alpha on thyroid autoimmunity and function have to be investigated in basic research.     

Subclinical thyroid dysfunction in the elderly.

Subclinical thyroid dysfunction is more common in older persons. By definition, these disorders are recognized by isolated elevation or suppression of the serum TSH concentration, in association with a normal serum free thyroxine level. Among individuals over 65 years old, subclinical hypothyroidism is found in approximately 10% of women and approximately 3% of men. It is most commonly due to autoimmune thyroiditis or previous treatment for hyperthyroidism. There may be three indications for L-thyroxine therapy: (a) presence of antithyroid antibodies, indicating substantial risk of progression to over hypothyroidism; (b) symptoms consistent with thyroid hormone deficiency; and (c) an elevated serum LDL-cholesterol. Subclinical hyperthyroidism is present in approximately 1%-2% of older persons. The most common cause is excessive thyroid hormone therapy, followed by mild endogenous hyperthyroidism due to Graves' disease or nodular goiter. These can be differentiated from other causes of low serum TSH concentration based on clinical and other laboratory and radionuclide scan criteria. The most serious consequences of subclinical hyperthyroidism are atrial fibrillation and osteoporosis, to which elderly patients are particularly predisposed.     

Thyroid Function Abnormalities and Cognitive Impairment in Elderly People: Results of the Invecchiare in Chianti Study

OBJECTIVES: To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition.
DESIGN: Cross-sectional.
SETTING: Community-based.
PARTICIPANTS: One thousand one hundred seventy-one men and women aged 23 to 102.
MEASUREMENTS: Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 vs ≥65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders.
RESULTS: Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P <.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P <.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61±6.88 vs 24.72±4.52, P <.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P =.003).
CONCLUSION: Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment.     

Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon-α therapy

BACKGROUND AND AIMS Hepatitis C virus is involved in the induction of autoimmunity and interferon can also induce hepatic and non-hepatic autoimmune reactions. This study assessed the prevalence of thyroid autoantibodies and autoimmune thyroid disorders in patients with chronic hepatitis C before and during interferon therapy. PATIENTS AND METHODS We studied prospectively 207 patients positive for anti-HCV and viral RNA. One hundred and forty-four of them received a therapeutic trial of one year with interferon-α. Free thyroxine, TSH and autoantibodies to thyroglobulin and thyroid microsomes were systematically tested at entry and at weeks 12 and 24 in both untreated and treated patients. RESULTS Sixteen of the 207 patients (7.7%) had thyroid dysfunction, including positive antithyroid antibodies in 14 (6.7%) and hypothyroidism in 10 (4.8%) prior to interferon therapy. In addition, during pretreatment evaluation one patient developed clinical hyperthyroidism after transient subclinical hypothyroidism and another had subclinical hyperthyroidism. Prevalences of positive antithyroid antibodies and hypothyroidism were significantly higher in women (14.7 and 10.5%, respectively, vs 0% in men, P < 0.01) and were directly associated with increasing age (P < 0.01). The incidence of thyroid dysfunction was also significantly higher in patients with other autoantibodies such as anti-nuclear (ANA) (P < 0.01). A trial with interferon was initiated in 144 patients and 8 of 142 (5.6%) without previous thyroid abnormalities developed thyroid dysfunction, including positive antithyroid antibodies in 7 (4.9%) and hypothyroidism in 4 (2.8%) with a prevalence again significantly higher in women (12.7 and 8.3%, respectively, vs 1% in men, P < 0.01) and also directly related to increasing age (P < 0.01). An association was found between the development of thyroid dysfunction during interferon therapy and the presence of other autoantibodies, including ANA, anti-DNA and anti-Sjögren’s antibodies (P < 0.01), as well as with the induction of autoimmune hepatitis and Sjögren's syndrome (P < 0.01 and < 0.05 respectively). Thyroid abnormalities were reversed in all patients when interferon therapy was discontinued. CONCLUSIONS No significant association was found between chronic hepatitis C and the presence of thyroid autoimmunity in female patients. On the contrary, interferon therapy induced antithyroid autoantibodies and thyroid dysfunction de novo in patients with chronic hepatitis C without pre-existing thyroid abnormalities. Thyroid dysfunction secondary to interferon was reversible after discontinuation of therapy.     

Thyroid function and changes in ultrasound morphology during antiviral therapy with pegylated interferon and ribavirin in patients with chronic hepatitis C

Summary. Thyroid disease is a common side‐effect of interferon‐based antiviral therapy for chronic hepatitis C, which may lead to dose reduction or discontinuation of therapy. The aim of this study was to investigate changes in ultrasound morphology, thyroid function, autoimmunity as well as predictive factors for the development of thyroid dysfunction in patients with hepatitis C virus infection treated with pegylated interferon‐α (PEG‐IFN‐α) and ribavirin. A total of 59 patients with chronic hepatitis C assigned for antiviral treatment with PEG‐IFN‐α and ribavirin were enrolled into the study. All patients were subjected to an ultrasound examination of the thyroid gland before treatment, and after 1, 3 and 6 months of antiviral therapy. In addition, thyroid function and autoimmune status were determined at fixed time‐points. Prior and during the course of therapy, 11 patients (19%) developed thyroid dysfunction (one hypothyroidism, nine hyperthyroidism, one hyperthyroidism followed by hypothyroidism). Hyperthyroidism was shown to be Graves’ disease in one patient and destructive thyroiditis in nine patients. Power‐Doppler ultrasound could differentiate between destructive thyroiditis and Graves’ disease. A reduction in echogenicity suggestive for a destructive process of the thyroid gland was observed even before changes in thyroid function of antibody status could be measured. Risk factors for the development of thyroid dysfunction were age, female gender, pre‐treatment thyroid volume, pre‐existing thyroglobulin/thyroid peroxidase antibodies and viral load. Changes in thyroid function are a common side‐effect occurring during antiviral therapy with PEG‐IFN‐α and ribavirin. Ultrasound presents a simple complementary tool for screening and follow‐up during antiviral therapy, which helps to differentiate between the common types of hyperthyroidism and gives insight into morphological changes of the thyroid gland during antiviral therapy.     

No association between HIV disease and its treatment and thyroid function

OBJECTIVES: The aims of the study were (i) to investigate the prevalence of overt and subclinical thyroid disease in HIV-positive patients in a London teaching hospital; (ii) to determine risk factors associated with the development of thyroid dysfunction, including highly active antiretroviral therapy (HAART) and individual antivirals, and (iii) to determine the occurrence of thyroid dysfunction longitudinally over 3 years. METHODS: The study consisted of retrospective analyses of thyroid function tests (TFT) in HIV-positive patients. The period prevalence of and factors associated with clinical and subclinical thyroid dysfunction were investigated. Patients with normal TFT but previous thyroid disease were identified from pharmacy records and included in the overt category. RESULTS: A total of 1565 patients (73% of the clinic population) had at least one TFT taken since 2001. Overall, 3584 samples were analysed. Of the patients included in the study, 1233 (79%) were male, 1043 (66%) were white and 365 (23%) were black African, and in 969 (62%) the main risk for HIV was homosexual sex. Median age at baseline was 37 years. Nine hundred patients (58%) were on HAART at the start of the study. Thirty-nine (2.5%) were found to have overt hypothyroidism, and eight (<1%) had overt hyperthyroidism. Sixty-one (4%) had subclinical hypothyroidism, five (<1%) had subclinical hyperthyroidism and 263 (17%) had a nonthyroidal illness. A normal TFT was obtained for 1118 patients (75.5%). Multivariate analysis suggested that no independent variables were significantly associated with overt hypothyroidism, including HAART and stavudine use specifically. Repeated measurements over 3 years were available for 825 patients and only eight new cases (1%) of overt thyroid disease occurred. CONCLUSIONS: The prevalence of overt thyroid disease was low in this cohort, suggesting that screening is not warranted.     

The immunofluorometric TSH assay as first-line test for suspected thyroid dysfunction

In this study of 103 patients with suspected thyroid dysfunction, the diagnostic value of a single basal immunofluorometric (IFMA) TSH measurement was evaluated and compared with the classical TRH test with RIA-TSH measurements, plasma TT4 concentrations and FT4I. A single basal TSH determination accurately predicted the TRH-stimulated TSH response, making the TRH test redundant in most patients. Because undetectable basal TSH did not always exclude a small rise in TSH, the TRH test could still be indicated in patients receiving thyroxine suppression therapy for thyroid cancer. Basal TSH differentiated accurately between euthyroidism and thyroid dysfunction, especially at the decision values of 0.20 and 4.0 mU/l, as proposed in this study. For diagnosis of clinical and subclinical hypo- and hyperthyroidism, additional measurement of TT4 and/or FT4I is necessary. A 2-yr follow-up of patients with subclinical thyroid dysfunction did not show progression to clinical disease. In some of the patients with subclinical hypothyroidism, substitution therapy with thyroxine had been started after initial testing. Indications for treatment of subclinical thyroid dysfunction are discussed.     

Prevalence of thyroid dysfunction in Thai HIV-infected patients

Increasing prevalence of thyroid function abnormality has been reported in HIV-infected patients. We aim to evaluate the prevalence and assess risk factors of thyroid dysfunction in Thai HIV-infected patients. A cross-sectional study was conducted. Serum thyroid hormone concentrations (FT4, FT3, and TSH) and thyroid autoantibodies (TgAb and TPOAb) were measured by electrochemiluminescence immunoassay. A total of 200 HIV-infected outpatients were included. Ninety-seven patients (48.5%) were men (mean age of 36.3 +/- 8.3 years). Duration of HIV infection was 49.6 +/- 35.1 months and 53% had previous opportunistic infections (OI). Mean CD4 cell count was 340.6 +/- 173.1 cells/mm(3). Of these, 167 patients (83.5%) received antiretroviral therapy (ARV). Abnormal thyroid function test was detected in 32 patients (16%). Twenty-seven patients (13.5%) had decreased thyroid function (primary hypothyroidism 3, subclinical hypothyroidism 12, and low FT4 with low or normal TSH 12) whereas 5 patients had increased thyroid function (overt hyperthyroidism 1, subclinical hyperthyroidism 1, and isolated high FT3 3). None had clinical features of thyroid hormone dysfunction. Thirteen patients (6.5%) had thyroid antibody positive. Patients who received ARV had higher mean FT3 levels than those who were na?ve to ARV (p = 0.017). History of previous OI was found to be an independently significant risk factor for decreased thyroid function with the odds ratio of 3.28 (95% CI =1.183-9.099; p = 0.022). Hypothyroidism was common among Thai HIV-infected patients, especially in those who had history of previous OI. It is therefore suggested that screening and/or monitoring of thyroid hormone in HIV-infected patients should be considered.     

Pegylated interferon-alpha2beta in combination with ribavirin does not aggravate thyroid dysfunction in comparison to regular interferon-alpha2beta in a hepatitis C population: meta-analysis

BACKGROUND: Interferon (IFN) has been well documented to cause thyroid dysfunction, especially in high risk patients and when combined with ribavirin (RBV). There is very sparse data to assess if pegylated IFN will further aggravate the thyroid disease risk in comparison to regular IFN. The purpose of this study was to assess the risk of developing thyroid disease with pegylated IFN (pIFN) versus regular IFN (rIFN) therapy (in combination with RBV). We also pooled our results with previous studies in a meta-analysis. METHODS: An observational study was made retrospectively of 24 patients who underwent a combination of rIFN and RBV therapy for hepatitis C virus (HCV) infection. As these patients failed to obtain an initial satisfactory response, they were retreated using pIFN and RBV. Monthly thyrotropin (TSH) levels were assessed while undergoing both treatment regimens. A meta-analysis was performed using available published data in PubMed. RESULTS: No difference in TSH levels was observed when comparing rIFN/RBV with pIFN/RBV. None of the patients developed hypo- or hyperthyroidism. TSH levels fluctuated during the treatment but did not extend outside the reference range. No further investigation was carried out in the absence of clinical and biochemical thyroid disease. The result of the meta-analysis failed to find any excess risk of thyroid dysfunction using pIFN above that of rIFN. CONCLUSIONS: The pegylation of IFN, in combination with RBV, did not aggravate thyroid diseases in the hepatitis C population. This finding is reassuring and dictates that no deviation from current practice regarding thyroid surveillance is required whilst undergoing HCV treatment.     

Study of the effect of antiviral therapy on homocysteinemia in hepatitis C virus- infected patients

ABSTRACT: BACKGROUND: Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease (CLD). About 80% of those exposed to the virus develop a chronic infection. Hyperhomocysteinemia, which is an independent risk factor for atherosclerotic vascular disease and thromboembolism, may develop in HCV-infected patients although altered alanine amino transferase (ALT) enzyme levels are generally associated with damage to liver cells. The gold standard therapy for chronic hepatitis C patients is pegylated interferon combined with an anti-viral drug (ribavirin). The current study aimed to investigate the effect of antiviral therapy on plasma homocysteine (Hcy) levels in HCV patients in addition to other parameters. METHODS: 532 HCV-infected patients and 70 healthy controls were recruited for the study. All patients were subjected to laboratory investigations including HCV-RNA levels, complete blood cell counts, serum levels of homocysteine, ALT, alkaline phosphatase (ALP), lipid profile and liver ultrasonographic examination. The outcome of treatment with pegylated interferon alpha plus ribavirin treatment and sustained virologic response (SVR) was determined 6--9 months post-therapy. RESULTS: Hyperhomocysteinemia was found in 91.35% of HCV-infected patients. The difference in plasma Hcy concentrations reached statistical significance between the patient and control groups. ALT, cholesterol and triglycerides (TGs) levels were found higher than normal in the patients group. After receiving a combined therapy for 24 weeks, 43.66% patients showed an SVR (responders); 30.98% patients were non-responders while 25.35% patients initially responded to therapy but again retrieved positive status of HCV infection six months post-therapy (relapse-cirrhotic patients). The mean levels of plasma Hcy, ALT and ALP were significantly reduced in responders within 10 weeks of therapy when compared with non-responders and relapse-cirrhotic patients. CONCLUSION: Elevated homocysteine levels in serum due to HCV infection can be reduced to normal range with the standard interferon alpha plus ribavirin treatment. This study highlights the significance of the measurement of serum homocysteine levels in the diagnosis and monitoring of HCV infection treatment in addition to other laboratory parameters.     

Evaluation of thyroid functions with respect to iodine status and TRH test in chronic autoimmune thyroiditis

Objective: Chronic autoimmune thyroiditis (CAT) is the most common form of thyroiditis in childhood and a frequent cause of acquired hypothyroidism. The objective of this study was to evaluate the thyroid status of childrenand adolescents with CAT with respect to iodine status and diagnostic values of thyrotropin-releasing hormone (TRH) test. Methods: Seventy-one children (mean age: 11.6 years) were studied in a retrospective analysis. Free thyroxine (T4), thyrotropin (TSH), TSH response to TRH test, thyroid autoantibodies, thyroid sonography, and urinary iodine excretion (UIE) were evaluated. Results: At diagnosis, 8.5% of patients had overt hypothyroidisim and 36.6% subclinical hypothyroidism; 5.6% had overt hyperthyroidisim and 8.5% had subclinical hyperthyroidism. Of them, 40.8% were euthyroid. Median UIE was 51 mg/L in overt hypothyroidism and 84 mg/L in subclinical hypothyroidism. The values were 316 mg/L and 221 mg/L in overt and subclinical hyperthyroidism, respectively. Basal TSH showed a strong correlation with peak TSH level on TRH test. Thirty-four percent of patients with normal basal TSH level showed an exaggerated TSH response. Conclusion: Iodine deficiency was seen more in cases with hypothyroidism, while excess of iodine was observed to be more frequent in hyperthyroid patients. Iodine status was a strong predictorof the thyroid status in CAT. TRH test may be helpful in further delineating patients with subclinical hypothyroidism. Conflict of interest:None declared.     

Socio demographic wise risk assessment of thyroid function abnormalities in far western region of Nepal: A hospital based descriptive study

Objective

To know the status of thyroid disorder in population of far western region of Nepal.

Methods

A total of 808 cases (133 men and 675 non pregnant women) were included and study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Nepalgunj Teaching Hospital between 1st January, 2011 and 28th February, 2012. The variables collected were age, sex, and thyroid function profile including free T3, free T4 and TSH.

Results

The percentage of thyroid disorders was 33.66% in far western region of Nepal. The people were highly affected by overt hyperthyroidism (14.9%) followed by subclinical hyperthyroidism (9.9%). The subclinical hypothyroidism was 7.9% while 1% overt hypothyroidism only in a far western region of Nepal. Females were highly affected by overt hyperthyroidism (17.8%), followed by subclinical hyperthyroidism (11.9%). A total of 5.9% females were affected by subclinical hypothyroidism while only 1.2% by overt hypothyroidism. Males were affected only by subclinical hypothyroidism (18.0%) in this present study. High number of total thyroid dysfunction was observed in 21 to 40 years of age groups, followed by 41 to 60 years of age groups. Less than 40 years people were having 1.03, 0.99, 2.51 and 1.15 times risk of developing overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism and subclinical hyperthyroidism respectively compared to greater than 40. Female were having 0.29 times risk of developing subclinical hyperthyroidism compared to male. But overt hyperthyroidism, subclinical hyperthyroidism and overt hypothyroidism female were having more risk of developing compared to male.

Conclusions

The thyroid disorder, especially overt hyperthyroidism (14.9%) and subclinical hyperthyroidism (9.9%) was high. Further studies are required to characterize the reasons for this high prevalence.