甲状腺自身免疫致不孕流产的机制

母体甲状腺自身免疫与不孕、流产、早产及新生儿智力发育障碍密切相关,是导致育龄期妇女甲状腺功能障碍的主要原因.甲状腺自身免疫导致女性不孕与流产的机制,包括T细胞异常、自然杀伤细胞高度活化、多克隆B细胞激活、维生素D缺乏以及甲状腺自身抗体与甲状腺外位点交叉反应学说等.存在甲状腺自身免疫的妇女,不论是否存在甲状腺功能障碍,给予左甲状腺素或硒制剂治疗都可能会改善妊娠结局.因此,筛查和治疗甲状腺自身免疫的育龄女性会优化生殖、生育.     

Is systematic screening for thyroid disorders indicated in subfertile men?

CONTEXT: Data on the prevalence of thyroid disorders in male subfertility remain scarce. OBJECTIVE: To investigate the prevalence of thyroid dysfunction and thyroid autoimmunity in men with normal and abnormal semen characteristics. SETTING: Tertiary referral center for reproductive medicine of the University Hospital AZ-VUB, Brussels, Belgium. PATIENTS AND DESIGN: Two hundred and ninety-two men were stratified according to the presence of normal (group 1; n = 39) or abnormal (group 2; n = 253) semen characteristics. Thyroid function was assessed by serum thyrotropin (TSH) and free thyroxine (FT4), and thyroid peroxidase antibodies (TPO-Ab) for thyroid autoimmunity (TAI or TPO-Ab > 34 kU/l); both were correlated with semen characteristics. MAIN OUTCOME MEASURES: Semen characteristics were determined by World Health Organisation criteria (rapid + slow motility > or = 50% and concentration > or = 20 x 10(6)) and Kruger criteria (morphology > or = 14% normal cells). RESULTS: In group 1, the mean (+/- s.d.) age was 33 +/- 4 years; serum TSH was 1.6 (0.3-29.6) mU/l (median (range)) and FT4 was 12.2 (8.8-15.6) ng/l. In group 2, the mean age was 33 +/- 5 years, serum TSH was 1.3 (0.3-5.2) mU/l and FT4 was 12.5 (8.4-17.5) ng/l; (compared with group 1 P = 0.008 for TSH and P = 0.037 for FT4). In both groups, one patient had increased TSH (2.6% and 0.4%; P = not significant (ns)). In group 1, one patient had TAI and in group 2 twelve patients had TAI (2.6% compared with 4.7%; P = ns). FT4 was an independent determinant for semen characteristics. CONCLUSIONS: The prevalence of thyroid dysfunction and autoimmunity is comparable between men with normal and abnormal semen characteristics. On the basis of these data, we do not advise systematic screening for thyroid disorders in subfertile men consulting a tertiary referral center for reproductive medicine.     

HIV infection and subfertility

With the improvements in life expectancy and quality of life for HIV-infected individuals in the developed world, and the increasing rates of HIV transmission among heterosexuals, reproductive issues are becoming increasingly important. We discuss the management of conception and pregnancy in HIV-infected couples. Couples where one or both partners are HIV infected may also experience subfertility and in this article we review the methods available to treat subfertility in this population and the current guidelines for the use of these techniques. HIV-infected couples can enjoy normal, healthy lives and should have access to the same investigation and treatment as their HIV-negative counterparts. Current inequities in the treatment available must be addressed.     

Thyroid disorders in infertile women.

Thyroid hormones have profound effects on reproduction and pregnancy. There is a known association of hyper- and hypothyroidism with menstrual disturbances and decreased fecundity. Women with reproductive failure also have an increased prevalence of organ specific autoimmunity compared to fertile women. The present study aims to answer the following questions: 1) is there an increased prevalence of thyroid antibodies in infertile women? 2) are thyroid antibodies associated with a particular cause of infertility? and 3) do these antibodies influence outcome of the in vitro fertilization procedure? The answers to the two first questions were evaluated with a case-control study looking at the occurrence of thyroid autoimmunity and thyroid function tests among women of infertile couples (n=438), presenting for the first time at the department of reproductive medicine. For comparison, a control population of parous women (n=100), matched for age, was included. In 45% of the infertile couples a female cause of infertility was identified: endometriosis (11%), tubal disease (30%) and ovarian dysfunction (59%). Male infertility was diagnosed in 38% and idiopathic infertility in 17% of the couples. Mean serum TSH levels were significantly higher in patients with infertility compared with control patients: 1.6 +/- 2.6 versus 1.2 +/- 0.7 mIU/L. The proportion of positive TPO-Abs was higher in all women of infertile couples, compared with controls (14% versus 8%), but the difference was not significant. Considering only the female causes of infertility a significant higher proportion of women had positive TPO-Abs compared with controls (18% versus 8%), and in particular a high prevalence of thyroid autoimmunity was found in women suffering from endometriosis (29%). Both hypo- and hyperthyroidism were more frequent when TPO-Abs were positive, compared to women without thyroid autoimmunity. The results of the present study indicate that endometriosis, increases the relative risk for associated thyroid autoimmunity to 2.3, and therefore screening for thyroid auto-antibodies could be systematically proposed in these women.     

Long-term follow-up of 106 multiple sclerosis patients undergoing interferon-beta 1a or 1b therapy: predictive factors of thyroid disease development and duration

BACKGROUND: Conflicting data have been reported on the association between interferon (IFN)-beta therapy of multiple sclerosis (MS) patients and thyroid disease development. AIMS: The goals of this study are as follows: to assess the actual occurrence of thyroid dysfunction and autoimmunity during long-term IFN-beta therapy; to establish the possible presence of predictive factors for thyroid dysfunction development and duration; and to suggest an effective follow-up protocol for patients receiving long-term IFN-beta therapy. STUDY PROTOCOL: A total of 106 MS patients (76 women) underwent IFN-beta 1a or 1b therapy for up to 84 months (median, 42 months). Thyroid function and autoimmunity were assessed at baseline and every 3-6 months throughout the treatment course. RESULTS: Baseline thyroid autoimmunity was detected in 8.5% of patients and hypothyroidism in 2.8%. Thyroid dysfunction (80% hypothyroidism, 92% subclinical, 56% transient) developed in 24% (68% with autoimmunity) of patients and autoimmunity in 22.7% (45.5% with dysfunction), without significant differences between the two cytokines; 68% of dysfunctions occurred within the first year. Autoimmunity emerged as the only predictive factor for dysfunction development (relative risk, 8.9), whereas sustained disease was significantly associated with male gender (P < 0.003). CONCLUSIONS: Both incident thyroid autoimmunity and dysfunction frequently occur in MS patients during IFN-beta therapy, particularly within the first year of treatment. Thyroid dysfunction is generally subclinical and transient in over than half of cases; preexisting or incident autoimmunity emerged as the only significant predictive factor for thyroid dysfunction development. Thyroid function and autoimmunity assessment is mandatory within the first year of IFN-beta therapy; thereafter, serum TSH measurement only in patients with thyroid disease could be sufficient.     

Preconception management of thyroid dysfunction

Uncorrected thyroid dysfunction in pregnancy has well‐recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre‐empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves’ disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy.     

Prevalence of thyroid autoimmunity in sporadic idiopathic hypoparathyroidism in comparison to type 1 diabetes and premature ovarian failure

CONTEXT: Thyroid autoimmunity is the most common coexistent endocrinopathy in type 1 diabetes (T1D), Addison's disease, and premature ovarian failure (POF). Although the role of autoimmunity is being investigated in patients with sporadic idiopathic hypoparathyroidism (SIH), there is little information on coexistent thyroid autoimmunity. OBJECTIVE: Our objective was to assess the prevalence of thyroid peroxidase autoantibodies (TPOAb) and thyroid dysfunction in patients with SIH and its comparison with that in T1D, POF, and Hashimoto's thyroiditis (HT) and age- and sex-matched healthy controls (for SIH). DESIGN AND SETTING: We conducted a case control study in a tertiary care setting. PATIENTS AND METHODS: Subjects were consecutive patients with SIH (n = 87), T1D (n = 100), POF (n = 58), and HT (n = 47) and healthy controls (100 females and 64 males). Serum free T3, free T4, TSH, and TPOAb (normal < or = 34 IU/ml) were measured by electrochemiluminescence assay. Subjects with 1) serum TSH at least 5 microU/ml along with TPOAb more than 34 IU/ml; 2) TSH at least 10 microU/ml but normal TPOAb titers; or 3) Graves' disease were considered to have thyroid dysfunction. RESULTS: TPOAb positivity (> 34 IU/ml) in females was 14.6% in SIH, 24.1% in POF, and 42.1% in T1D compared with 76.6% in HT and 9% in healthy controls. The frequencies of TPOAb positivity and thyroid dysfunction in patients with SIH were comparable to those in control and POF groups, but significantly less than in T1D and HT groups. CONCLUSION: The frequencies of TPOAb and thyroid dysfunction were not significantly higher in patients with SIH than in healthy controls, unlike in patients with T1D and POF.     

Thyroid dysfunction and thyroid autoimmunity in Saudi type 2 diabetics

Abstract Diabetes mellitus and thyroid disease are common endocrine disorders in the general population. To investigate the association between thyroid dysfunction, thyroid autoimmunity and Saudi type 2 diabetics, a random sample of 100 Saudi type 2 diabetics and 100 age- and sex-matched controls were studied. The mean age was 54 years for diabetics and 55 years for controls while the male:female ratios were 1:1.6 and 1:14 respectively. GAD65ab were found in 26% diabetics and 2% controls (p=0.001). Thyroid autoimmunity were detected in 10% diabetics vs. 5% controls (p=0.05), while thyroid dysfunction was found in 16% and 7% respectively (p=0.03). In GAD65ab-positive diabetics, thyroid autoimmunity was observed in 27% vs. 4% GAD65ab-negative diabetics (p=0.02) and thyroid dysfunction was reported in 42% and 7% respectively. We conclude that thyroid dysfunction and autoimmunity are common in Saudi type 2 diabetics. Further studies are needed on the cost effectiveness of thyroid screening in diabetics.     

Effect of 1-year treatment with interferon-beta1b on thyroid function and autoimmunity in patients with multiple sclerosis.

OBJECTIVE: Interferon-beta (IFN-beta) is a widely used therapy for multiple sclerosis (MS), a demyelinating disease of the central nervous system. This study has evaluated the effect on thyroid function and autoimmunity of a 1-year treatment with IFN-beta1b in patients with MS. PATIENTS: We studied 31 patients (age 34+/-7 years, 21 women) with relapsing-remitting MS during IFN-beta1b treatment of 1 year duration. Systematic thyroid assessment and measurements of serum interleukin-6 (IL-6) levels were performed at baseline and every 3 months during treatment. RESULTS: Sixteen percent of the patients had autoimmune thyroiditis before IFN-beta1b, all positive for anti-peroxidase antibodies. The overall incidence of thyroid dysfunction was 33% over 1 year (10% hyperthyroidism, 23% hypothyroidism). Thyroid autoimmunity developed in 5/26 patients (19%), in one case without dysfunction. In addition to autoantibody positivity at baseline, female gender and the presence of an ultrasound thyroid pattern suggestive of thyroiditis were identified by multiple logistic regression as additional risk predictors for the development of thyroid dysfunction. During IFN-beta1b treatment, serum IL-6 levels rose in a consistent biphasic pattern; there was, however, no difference between patients with or without incident thyroid abnormalities. CONCLUSIONS: We conclude that IFN-beta1b therapy can induce multiple alterations in thyroid function, some of which are unrelated to thyroid autoimmunity. IL-6 measurement is not useful to identify patients prone to develop thyroid abnormalities. Though thyroid dysfunction is generally subclinical and often transient, systematic thyroid assessment should be performed during IFN-beta1b treatment.     

Polyglandular autoimmune syndromes

Dysfunction of multiple endocrine glands may develop as the result of hypopituitarism, various infiltrative disorders, or an organ-specific autoimmune mechanism. When dysfunction of two or more endocrine glands occurs in association with circulating organ-specific antibodies directed against the involved glands, the term polyglandular autoimmune syndrome is applied. Characteristics of polyglandular autoimmunity include specific patterns of disease association and frequently a family history of similar involvement. The principal endocrine components of these syndromes are adrenal insufficiency, autoimmune thyroid disease, insulin-dependent diabetes mellitus, and premature gonadal failure. In addition, primary hypoparathyroidism is a key feature of one form of polyglandular autoimmunity that occurs in children. Several nonendocrine organ-specific autoimmune disorders are also associated with polyglandular autoimmunity, of which pernicious anemia is the most frequent. The underlying abnormality responsible for polyglandular autoimmunity is most likely a defect in T suppressor cell function, but there is evidence that aberrant expression of HLA DR antigens also plays an important role in the pathogenesis of these disorders.     

The role of thyroid autoimmunity in fertility and pregnancy

The thyroid gland and gonadal axes interact continuously before and during pregnancy. Hypothyroidism influences ovarian function by decreasing levels of sex-hormone-binding globulin and increasing the secretion of prolactin. In women of reproductive age, hypothyroidism can be reversed by thyroxine therapy to improve fertility and avoid the need for use of assisted reproduction technologies. For infertile women, preparation for medically assisted pregnancy comprises controlled ovarian hyperstimulation that substantially increase circulating estrogen concentrations, which in turn can severely impair thyroid function. In women without thyroid autoimmunity these changes are transient, but in those with thyroid autoimmunity estrogen stimulation might lead to abnormal thyroid function throughout the remaining pregnancy period. Prevalence of thyroid autoimmunity is significantly higher among infertile women than among fertile women, especially among those whose infertility is caused by endometriosis or ovarian dysfunction. Presence of thyroid autoimmunity does not interfere with normal embryo implantation, but the risk of early miscarriage is substantially raised. Subclinical and overt forms of hypothyroidism are associated with increased risk of pregnancy-related morbidity, for which thyroxine therapy can be beneficial. Systematic screening for thyroid disorders in pregnant women remains controversial but might be advantageous in women at high risk, particularly infertile women.     

Thyroid function and autoimmunity during interferon beta-1b treatment: a multicenter prospective study

Thyroid dysfunction and autoimmunity have been reported during type I interferon therapy, namely interferon-alpha for chronic hepatitis or interferon-beta for multiple sclerosis. To define the frequency of thyroid dysfunction and autoimmunity during interferon-beta treatment, 156 multiple sclerosis patients were prospectively followed up by 18 centers for 1 yr after starting interferon-beta-1b treatment. Serial clinical assessments and tests of thyroid and liver function and antithyroid autoantibodies (all performed by the same centralized laboratory) were conducted every 3 months. TSH and antithyroid autoantibodies against human TG or thyroid microsomal antigens were measured by immunoradiometric methods; free T3 and T4 were measured by chromatographic assays. Longitudinal occurrence of thyroid or liver alterations or of autoantibodies was analyzed with the generalized estimating equations method, correcting for the correlation of repeated measurements of the same subject over time. Pretreatment comparison with a control group of 437 healthy blood donors did not show significant differences in the frequency of thyroid dysfunction or antithyroid autoantibody positivity. During interferon-beta treatment, the de novo frequency of thyroid alteration was 8.3%, that of liver alteration was 37.5%, and that of antithyroid autoantibody was 4.5%. Generalized estimating equations analysis demonstrated that the frequency of liver alteration significantly increased during treatment compared with the baseline value (odds ratio, 7.03; confidence interval, 2.49-19.9), whereas that of thyroid alteration or of antithyroid autoantibodies did not. The frequency of thyroid dysfunction during interferon-beta treatment showed random, nonsignificant changes over time and, in addition, was not correlated to antithyroid autoantibody positivity.     

High prevalence of autoimmune thyroid disease in pulmonary arterial hypertension

STUDY OBJECTIVES: An association between thyroid disease and pulmonary arterial hypertension (PAH) has been reported, yet the pathogenetic relationship between these conditions remains unclear. Because immune system dysfunction may underlie this association, we sought to determine the prevalence of autoimmune thyroid disease (AITD) in patients with PAH. DESIGN AND SETTING: Prospective observational study at a single academic institution. PATIENTS: Sixty-three consecutive adults with PAH (ie, sustained pulmonary artery systolic pressure, > 25 mm Hg) were evaluated for clinical, biochemical, and serologic features of AITD. MEASUREMENTS: Thyroid gland dysfunction was determined by clinical examination for goiter, and by biochemical measurements of thyrotropin and free thyroxine. Immune system dysfunction was determined by serologic measurements of antibodies to thyroglobulin and thyroid peroxidase. First-degree family history of AITD also was ascertained in order to investigate for genetic clustering of autoimmunity. RESULTS: Thirty-one patients (49%; 95% confidence interval [CI], 37 to 62%) received diagnoses of AITD. Eighteen patients were newly diagnosed, and 9 patients required the initiation of pharmacologic treatment. There was no chronologic relationship between the diagnosis or treatment of PAH and that of AITD. Sixteen patients (25%; 95% CI, 15 to 36%) had 24 first-degree family members with AITD. CONCLUSIONS: Approximately half of the patients with PAH have concomitant AITD. These two conditions may be linked by a common immunogenetic susceptibility, and the elucidation of this association may advance the understanding of the pathophysiology and treatment of PAH. Systematic surveillance for occult thyroid dysfunction in patients with PAH may prevent the hemodynamic exacerbation of right heart failure.     

Thyroid autoimmunity in chronic urticaria.

A subset of patients with idiopathic chronic urticaria (CU) has been recently classified as autoimmune on the basis of two main findings: association with thyroid autoimmunity and with anti-IgE and/or anti-IgE receptor antibodies. The association of CU with thyroid autoimmunity has been known since 1983, but its frequency varies in different reports. The objective of the present study was to verify the prevalence of thyroid antibodies (anti-thyroid peroxidase, TPO; thyroglobulin, TG; TSH-receptor, TSH-R) in two distinct series of CU: of known cause (70 cases, group A) and idiopathic (52 cases, group B). Twenty-three patients (M/F:7/16) of group A (33%) and 12 (M/F:4/8) of group B (23%) tested positive for at least one type of thyroid antibody. The difference was not statistically significant. Thyroid disease or altered serum TSH levels (requiring treatment) were present in 39% of group A and 42% of group B seropositive patients. In conclusion, the present study shows that CU, either of known cause or idiopathic, is more common in females than in males and is significantly associated with thyroid autoimmunity. These results were not expected on the assumption that autoimmune phenomena are a specific pattern of idiopathic CU. Thus, screening for thyroid autoimmunity and function is advisable in all patients with CU for the early identification of patients requiring either treatment of underlying thyroid dysfunction or follow-up.     

The Systematic Screening and Management of Hypothyroidism and Hyperthyroidism During Pregnancy

Altogether, thyroid function abnormalities during pregnancy can affect up to 10% of all women. The high prevalence of both hypo- and hyperthyroidism, the obstetrical repercussions associated with thyroid dysfunction in the mothers, as well as the potential role of maternal thyroid dysfunction as an influence on fetal development constitute solid arguments for a further increase of our knowledge of the pathophysiological processes underlying the alterations of thyroid function related to the pregnant state. In this review, the focus will be on the most clinically relevant aspects associated with hypothyroidism [autoimmune thyroid disorders (AITDs), subfertility, risk of miscarriage, risk of hypothyroidism in women with AITD and treatment of hypothyroid women] and with hyperthyroidism (clinical presentations during pregnancy, Graves' disease and its management, fetal hyperthyroidism in women with antithyroid-stimulating hormone receptor antibodies and gestational transient thyrotoxicosis associated with human chorionic gonadotropin stimulation of the maternal thyroid gland). I also propose a global strategy for the systematic screening of hypo- and hyperthyroidism in the pregnant state.     

Long-term outcome of interferon-alpha-induced thyroid autoimmunity and prognostic influence of thyroid autoantibody pattern at the end of treatment

Thyroid autoimmunity and dysfunction have been widely reported as side effects of interferon-alpha (IFN-alpha) treatment, but the literature lacks data regarding the long-term course of these complications, clinical observation being limited to 6-12 months off therapy. Our study is the first that has aimed to evaluate the natural history of IFN-related thyroid autoimmunity during a 6.2-yr follow-up after the IFN-alpha withdrawal as well as to investigate the potential role of the autoantibody pattern at the end of treatment to predict the long-term outcome. Our study group included 114 patients (79 males, 35 females), mean age 48 yr (range 23-67 yr) with no preexisting thyroid disease, undergoing a 12-month treatment with recombinant IFN-alpha for C virus-related chronic active hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb) and function (serum FT(4), FT(3), TSH) were retrospectively evaluated at the end of IFN therapy, 6 months after IFN withdrawal and after a median period of 6.2 yr (range 5.5-8.4 yr). At the end of treatment, 78 patients were negative for thyroid autoantibodies (Abs-) and all but one of them remained so for the following evaluations. The remaining 36 patients had thyroid autoantibodies (Abs+) at the end of treatment, and they subsequently showed a heterogeneous behavior: 16 patients remained Abs+ for the whole length of the study (persistent thyroiditis); 10 patients became Abs- 6 months off therapy but were again Abs+ 6.2 yr later (remitting/relapsing thyroiditis); 10 patients reverted to autoantibody negativity at different observation times (transient thyroiditis). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroiditis (odds ratio: 0.02, confidence interval (CI) 95%: 0-0.1). On the contrary, the positivity for TgAb and/or TPOAb at high titers at the end of IFN treatment was significantly related to the highest risk of having chronic thyroiditis (odds ratio: 17.3, CI 95%: 3.2-91.7 for TgAb levels > 50 degree percentile; odds ratio: 7.3, CI 95%: 1.5-35.2 for TPOAb levels > 50 degree percentile). None of the patients showed overt thyroid dysfunction throughout the study, whereas a subclinical hypothyroidism was found in 12 patients. In all 12 cases, the functional abnormality was accompanied by the presence of thyroid autoantibodies. Eight of these 12 patients belonged to the group with persistent thyroiditis (P < 0.05). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroid dysfunction (odds ratio: 0.06, CI 95%: 0.01-0.56). On the contrary, the positivity for both TgAb and TPOAb at the end of IFN therapy was significantly correlated with the highest risk of having subclinical hypothyroidism 6.2 yr. later (odds ratio: 38.7; CI 95%: 6.2-242). Our study demonstrates that in patients undergoing an IFN-alpha therapy for chronic hepatitis C and with no evidence of preexisting thyroid disease: 1) the negativity for thyroid autoantibodies after IFN treatment is a protective factor for the developing thyroid autoimmunity and/or dysfunction in following years; 2) the IFN-alpha-related thyroid autoimmunity is not a complete reversible phenomenon because some patients can develop chronic thyroiditis; 3) high autoantibody levels at the end of IFN therapy are related to the risk of having chronic thyroid autoimmunity; and 4) the coexistence of TgAb and TPOAb at the end of treatment is a predictive factor for the presence of thyroid dysfunction, even if subclinical, many years after IFN withdrawal.     

Serum CXCL10 levels and occurrence of thyroid dysfunction in patients treated with interferon-alpha therapy for hepatitis C virus-related hepatitis

OBJECTIVE: Thyroid autoimmunity is a common side effect of interferon-alpha (IFN-alpha) treatment for chronic hepatitis C. There are currently no reliable parameters to predict the occurrence of thyroid dysfunctions in patients undergoing IFN-alpha therapy. CXC chemokine ligand 10 (CXCL10) is a chemokine known to play a role in both thyroid autoimmune disease and hepatitis C virus (HCV) hepatitis. DESIGN: The aim of this study was to evaluate serum CXCL10 levels in HCV patients treated with IFN-alpha in relation to the occurrence of thyroid dysfunctions. Serum CXCL10 levels were assayed in 25 HCV patients (proven to be negative for serum thyroid antibodies) before and during IFN-alpha therapy (2, 4 and 6 months) and in 50 healthy controls. HCV patients were retrospectively selected according to the occurrence of IFN-alpha-induced thyroid dysfunction and were assigned to two groups. Group I included 15 patients who did not develop thyroid antibody positivity or dysfunction; group II included ten patients who showed the appearance of serum thyroid antibodies, followed by clinically overt thyroid dysfunction. RESULTS: Patients with HCV, regardless of the development of thyroid dysfunctions, had significantly higher serum CXCL10 than controls (261.6+/-123.4 vs 80.4+/-33.6 pg/ml; P<0.00001). Pretreatment mean serum CXCL10 levels were significantly higher in Group I versus Group II (308.6+/-130.7 vs 191.1+/-69.4 pg/ml; P<0.05). Groups I and II showed different rates of favourable response to IFN-alpha treatment (33 and 90% respectively). CONCLUSION: Our results suggest that measuring serum CXCL10 before IFN-alpha treatment may be helpful for identifying those patients with higher risk to develop thyroid dysfunction, and require a careful thyroid surveillance throughout the treatment.     

Amiodarone-induced thyroid dysfunction in a tertiary center in south Brazil

Amiodarone, used in the treatment of cardiac arrhythmias, is associated with thyroid dysfunction. No reports exist on its frequency in southern Brazil, nor studies evaluating the usefulness of clinical scores to diagnose thyroid abnormalities in these patients. This study aimed at determining the prevalence of amiodarone-induced thyroid dysfunction in a representative sample from a tertiary center, to study the conditions associated to this dysfunction and to evaluate the reliability of clinical scores of hypo and hyperthyroidism. One hundred ninety-five amiodarone users were submitted to a clinical and laboratory evaluation. Of these, 2.1% were hyperthyroid, 25.1% hypothyroid and 9.2% had only a high T4. Considering thyroid dysfunction variables researched, thyroid autoimmunity was positively associated (OR 4.8; p= 0.02), and male gender had a trend to a positive association (OR 1.86; p= 0.06). Clinical scores were highly sensitive for hyperthyroidism (100%), but not for hypothyroidism (8%). The low prevalence of amiodarone-induced hypothyroidism suggests that this specific region is iodine-sufficient. All patients receiving chronic amiodarone therapy should be checked for clinical scores for hyperthyroidism and laboratory evaluation should be performed, as a screening for thyroid dysfunction, especially if they are male or have positive microsomal antibodies.     

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.     

Interferon-related thyroid autoimmunity and long-term clinical outcome of chronic hepatitis C

BACKGROUND: A high incidence of thyroid autoantibodies and/or disorders was observed in subjects with hepatitis C virus-related chronic hepatitis during interferon-alpha therapy. AIM: To evaluate whether thyroid autoimmunity and dysfunction, induced by interferon-alpha therapy, could be viewed as predictors for treatment response and as valid prognostic markers of liver disease progression. PATIENTS: A total of 136 subjects (96 males/40 females; median age 48 years; range 23-64) affected by biopsy-proven chronic hepatitis C (33.1% with compensated liver cirrhosis). METHODS: All subjects were treated with interferon-alpha therapy at 6 MU 3 times weekly for 12 months and then followed up for an average period of 60 months (range 12-108). Routine laboratory tests, virological assessment, liver ultrasound, thyroid function tests (serum free-triiodothyronine, free-thyroxine, serum thyrotropin), and autoimmunity were performed for all subjects. RESULTS: Percentage of thyroid autoimmunity and thyroid dysfunction in long-term responders was not significantly different compared to that in non-responders (47.0% and 11.8% vs 35.3% and 5.9%, respectively; non significant). The multivariate model demonstrated that the absence of cirrhosis was the only factor significantly related to successful response to therapy (odds ratio: 14.9; 95% confidence interval: 1.9-115.0 for chronic hepatitis C vs presence of cirrhosis). Moreover, the occurrence of thyroid autoimmunity during interferon therapy was similar both in patients with or without worsening of liver disease (33.3% and 39.8%, respectively; p = not significant). No subject with on-going liver disease developed thyroid dysfunction during treatment, as opposed to the 10/118 (8.4%) with a better course of liver disease; however, this difference was not statistically significant. The multivariate model showed that age was the only covariate significantly associated with unfavourable outcome of liver disease (odds ratio: 18.6; 95% confidence interval: 2.3-151.9, for those over 48 years vs younger patients). CONCLUSIONS: There is no evidence that the immune mechanism involved in the pathogenesis of thyroid autoimmune phenomena is the same as that regulating the therapeutic clearance of HCV or modulating the unfavourable course of HCV-related chronic hepatitis. However, our study confirmed that liver disease seems to progress more slowly in younger subjects.