Thyroperoxidase Autoantibodies Research Articles

Serum trace elements show association with thyroperoxidase autoantibodies in Thyroid Imaging Reporting and Data System (TI-RADS) 4 nodules

Thyroid nodule (TN) has been becoming a great concern worldwide due to its high incidence. Although some studies have reported associations between trace elements exposure and the risk of TNs, the linkage was not inconclusive. The present study aimed to identify the association of selected serum trace elements (Ca, Mg, V, Fe, Co, Cu, Zn, Se, Mn and Mo) with TNs among general adults. A cross-sectional study was conducted in January 2021 in Chengdu, China. 1282 subjects completed the questionnaire and gave at least one human biological material after an overnight fast, venous blood, and urine, including 377 TN participants defined through ultrasound. Various trace elements in serum specimens were determined by inductively coupled plasma mass spectrometry. Thyroid functions were tested by chemiluminescent microparticle immunoassay (CMIA). The associations between trace elements levels and the risk of TNs were examined by restricted cubic splines (RCS) regression and bayesian kernel machine regression (BKMR) models. TNs were more common in females (P < 0.001) and in the elderly (P < 0.001) and that they were also frequently associated with fertility, marital status, annual household income, drinking, anxiety, vitamin supplement, tea consumption, hypertension and hyperlipidemia. After adjusting for confounders by a propensity score matching model, the association between trace elements concentrations and TNs risk was found to be statistically insignificant in the RCS (P for nonlinear > 0.05) and BKMR models. FT3 or T4 (total or free) increased significantly with increasing total trace elements mixture levels. In TI-RADS-4 TN subjects, TPO-Ab level increased significantly with increasing total trace elements mixture levels in the high-dose range. Ca, Zn, Mo at their 75th percentile showed positive individual effects on TPO-Ab, which was examined to be interactive. The detection of trace elements for TNs in general adults may be of no significance, but once individuals classified as TI-RADS-4 TNs are detected with abnormal TPO-Ab, Ca, Zn and Mo level are recommended to measure. The substantive association on it still needs to be continuously explored in the future.

Normal thyroid volume in subjects evaluated in a primary ambulatory setting in Liguria.

Ultrasonography (US) is the simplest method of evaluating thyroid volume (TV). The current normal TV in Liguria is not known. The aim of this study was to obtain normative data on TV in Liguria, Italy. From 3552 files of endocrine evaluations registered in a primary outpatient setting, we selected 483 files on euthyroid subjects (383 females and 100 males) with a normal echoic pattern on US. The inclusion criterion was the absence of thyroperoxidase autoantibodies and drugs known to interfere with thyroid hormone secretion or metabolism. TV was calculated by means of US. Anthropometric characteristics, smoking habits and the district where subjects lived were registered. Less than 50% of patients were not taking any drug. The percentage of obesity was similar in both sexes. TSH levels were similar in males and females. Median TV was 8.0 mL (IQR: 6.7-9.8 mL) in females and 11.8 mL (9.3-15.6 mL) in males (P<0.0001). In females, TV was greater (P=0.01) in smokers than in non-smokers. In both sexes, the right lobe was significantly (P<0.0001) larger in volume than the left. Post-hoc analysis did not show any differences among age-groups in either females or males. In females, but not in males, TV differed significantly (P=0.0002) according to the district of residence. A significant positive correlation was found in both groups between TV and weight, height, BMI and BSA. Reference values of TV in the Ligurian population are now available. TV in the general population could be compared with these normative data.

Обоснование применения интервальной гипокситерапии в лечении женщин с аутоиммунным тиреоидитом

The purpose of the study was to evaluate the effects of interval hypoxic therapy in women with autoimmune thyroiditis (AIT) and hypothyroidism. Material and methods. 136 women with newly diagnosed AIT and hypothyroidism were examined and divided into two equal groups. The first group received hormonal replacement therapy with levothyroxine sodium for 12 months. The second group received levothyroxine sodium in combination with interval hypoxic therapy. Results. Levothyroxine sodium therapy in women with newly diagnosed AIT and hypothyroidism was associated with a further increase in the thyroperoxidase autoantibodies blood serum content (p &lt; 0.001). The combination with hypoxic therapy led to the lower autoantibodies values than levothyroxine sodium monotherapy (p &lt; 0.05). In addition, therapy with levothyroxine sodium was characterized by an increased need for medications (p &lt; 0.001). Hypoxic therapy supplementation in AIT provided the medication dose stabilization. Conclusions. It is appropriate to combine levothyroxine sodium with normobaric hypoxic therapy sessions (every 3 months for 10 days) in order to improve the effectiveness of autoimmune thyroiditis and hypothyroidism treatment in women.

Convulsive Seizures Revealing Hashimoto’s Encephalopathy

Introduction: Hashimoto encephalopathy (HE) is an autoimmune disease with different neurological and psychiatric characteristics. It is associated with increased thyroperoxidase autoantibodies. The diagnosis of HE is clinical and involves the detection of serum thyroperoxidase (TPO) antibodies and the exclusion of other etiologies. A clinical response to corticosteroid therapy supports the diagnosis. We report a case of HE revealed by convulsive seizures and cognitive and behavioral disorders. Observation: She is a 7-year-old child followed in a neurology unit for convulsive seizures for one year. Clinical examination performed in the endocrinology unit later found tachycardia without goiter, behavioral disorders, difficulties to concentrate as well as psychomotor agitation. Biological work up revealed subclinical hypothyroidism, positive anti-TPO antibodies with normal thyroid ultrasound and brain MRI. The cerebrospinal fluid was clear, normotensive and absence of pleocytosis. The sleep-wake electroencephalogram was well organized for her age with a paroxysmal discharge in the left parieto-temporal region. Based on these clinical, biological and morphological data, the diagnosis of HE was retained. Corticosteroid therapy with prednisone at 1 mg/kg/day was initiated for 6 weeks while reducing the dose progressively. There was a good clinical and biological progress under treatment. Conclusion: Hashimoto’s encephalopathy is a rare, but probably unrecognized entity. Over the past decades, knowledge about thyroid, brain, immunity interactions has increased. This indicates the importance of a multidisciplinary approach of endocrinologists, neurologists, psychiatrists and pediatricians for early recognition and treatment.

Normal thyroid volume in subjects evaluated in a primary ambulatory setting in Liguria.

Ultrasonography (US) is the simplest method of evaluating thyroid volume (TV). The current normal TV in Liguria is not known. The aim of this study was to obtain normative data on TV in Liguria. From 3552 files of endocrine evaluations registered in a primary outpatient setting, we selected 483 files on euthyroid subjects (383 females and 100 males) with a normal echoic pattern on US. The inclusion criterion was the absence of thyroperoxidase autoantibodies and drugs known to interfere with thyroid hormone secretion or metabolism. TV was calculated by means of US. Anthropometric characteristics, smoking habits and the district where subjects lived were registered. Less than 50% of patients were not taking any drug. The percentage of obesity was similar in both sexes. TSH levels were similar in males and females. Median TV was 8.0 ml (IQR 6.7 - 9.8 ml) in females and 11.8 ml (9.3 - 15.6 ml) in males (P<0.0001). In females, TV was greater (P=0.01) in smokers than in non-smokers. In both sexes, the right lobe was significantly (P<0.0001) larger in volume than the left. Post-hoc analysis did not show any differences among age-groups in either females or males. In females, but not in males, TV differed significantly (P=0.0002) according to the district of residence. A significant positive correlation was found in both groups between TV and weight, height, BMI and BSA. Reference values of TV in the Ligurian population are now available. TV in the general population could be compared with these normative data.

A Novel Mouse Model of Autoimmune Thyroiditis Induced by Immunization with Adenovirus Containing Full-Length Thyroglobulin cDNA: Implications to Genetic Studies of Thyroid Autoimmunity.

Background: Thyroglobulin (TG) is a key autoantigen in autoimmune thyroid diseases (AITD). Several single nucleotide polymorphisms (SNPs) in the TG locus were shown to be strongly associated with disease susceptibility in both humans and mice, and autoimmune response to TG is the earliest event in the development of thyroid autoimmunity in mice. The classical model of experimental autoimmune thyroiditis (EAT) is induced by immunizing mice with TG protein together with an adjuvant to break down immune tolerance. The classical EAT model has limited utility in genetic studies of TG since it does not allow testing the effects of TG sequence variants on the development of autoimmune thyroiditis. In this study, we have immunized CBA-J mice, an EAT-susceptible strain, with an adenovirus vector encoding the full-length human TG (hTG) to generate a model of EAT in which the TG sequence can be manipulated to test AITD-associated TG SNPs. Methods: We immunized CBA-J mice with hTG-expressing adenovirus following the well-recognized experimental autoimmune Graves' disease protocol that also uses an adenovirus vector to deliver the immunogen. Results: After hTG adenovirus immunizations, mice developed higher T cell proliferative and cytokine responses to hTG and TG2098 (a major T cell epitope in AITD) and higher titers of TG and thyroperoxidase autoantibodies compared with mice immunized with control LacZ-expressing adenovirus. The mice, however, did not develop thyroidal lymphocytic infiltration and hypothyroidism. Conclusions: Our data describe a novel murine model of autoimmune thyroiditis that does not require the use of adjuvants to break down tolerance and that will allow investigators to test the effects of hTG variants in the pathoetiology of Hashimoto's thyroiditis.

Assessment of serum thyroid hormone autoantibodies in the first trimester of gestation as predictors of postpartum thyroiditis

BackgroundMeasurement of serum thyroperoxidase autoantibodies (TPOAb) during gestation as a classical marker for the risk of postpartum thyroiditis (PPT) predicts PPT in 1/3 to 1/2 of women. Very few studies have measured serum thyroid hormone Ab (THAb) during gestation, and none as a possible marker for PPT. MethodsIn 412 women who were followed up from 7 to 11 weeks of gestation through 12 months after delivery, we measured THAb (T3.IgM, T3.IgG, T4.IgM, T4.IgG), thyroglobulin autoantibodies (TgAb) and TPOAb at study entry (7–11 week of gestation). ResultsSixty-three women (15.3%) developed PPT, which progressed to permanent hypothyroidism (PH) in 34/63 (54%). THAb+ve were 21/412 women (5.1%), the frequency being greater in those who then developed PPT (12/63 [19.0%] vs. 9/349 [2.6%], P = 4.6 × 10−8), and in the PH subgroup (26.5% [9/34] vs. 10.3% [10/29], P = 0.12). THAb positivity occurred in 9/76 women (11.8%) who were TgAb and/or TPOAb+ve compared to 12/336 women who were TgAb and TPOAb negative (3.6%, P = 0.0031). Of these 9 THAb+ve, TgAb and/or TPOAb+ve women, all (100%) developed PPT compared to 3/11 (27.3%, P = 0.0011) THAb+ve, TgAb and/or TPOAb negative women. Of these 9 and 3 PPT women, 8 and 1 progressed to PH (88.9% and 33.3%, respectively, P = 0.12). ConclusionsGestational positivity of THAb enhance enormously the predictivity for PPT of gestational positivity of TPOAb/TgAb. However, their low frequency (5.1%) and their sensitivity (17.5% [21/63]) go against their application in lieu of TPOAb/TgAb.

Relatively high rate of postpartum thyroiditis in the Straits of Messina area. Predictivity of both postpartum thyroiditis and permanent hypothyroidism by performing, in the first trimester of gestation, thyroid ultrasonography and measurement of serum thyroperoxidase and thyroglobulin autoantibodies

The prevalence of postpartum thyroiditis (PPT) averages 5%, with a range from 1% (Thailand) to 22% (Wales, UK, and Liguria, Italy), but 3.6% in another Italian region (Puglia). Evolution of PPT into permanent hypothyroidism (PH) occurs in approximately 50% of cases. Positive thyroperoxidase autoantibodies (TPOAb) in a pregnant woman is a strong predictor of PPT. Because in previous gestational cohorts we found an approximate 12% rate of TPOAb positivity, which compares with 15% in the Liguria cohort and 6% in the Puglia cohort, we hypothesized that the currently unknown prevalence of PPT in Sicily would approximate the said Liguria prevalence. We also explored the predictive value of serum thyroglobulin Ab (TgAb) positivity and ultrasonographic signs suggestive of thyroiditis (UST) at first trimester of gestation for PPT.Of 412 pregnant women who were followed-up for 1 year after delivery, 63 (15.3%) developed PPT, and 54% of them had PH. Gestational rates of TPOAb positivity alone, TgAb positivity alone or UST were 11.4%, 7.8% or 35.0%, with associated PPT rates of 66%, 45% or 36%. TgAb assay allowed detection of 9/63 PPT women (14.3%) who were TPOAb-negative. However, TPOAb remained a better predictor compared to TgAb or UST (odds ratio = 32 vs 10 or 13). Lowering the positivity threshold for either Ab to ≥61 U/ml, Ab-positive were 23.8% of PPT women and 17.7% of pH women. UST was detected in 82.5% of women who developed PPT, precisely 88% of those who evolved into PH and 75.9% of those who did not.Ours is the second study of the new millennium showing a PPT frequency >10%. The dual Ab and lowered threshold strategy correctly predicts more cases of PPT and PH compared to the sole TPOAb strategy. We confirm that half of the PPT women will have PH.

Marked improvement of thyroid function and autoimmunity by Aloe barbadensis miller juice in patients with subclinical hypothyroidism

Some natural compounds decrease serum levels of thyroid autoantibodies, but results are inconsistent and thyroid function has been evaluated infrequently; moreover, the effects of Aloe on thyroid autoimmunity and function have been examined in very few studies. This study stems from the observation of one co-author, who has Hashimoto’s thyroiditis (HT)-related subclinical hypothyroidism (SCH). Upon checking her biochemical thyroid panel when taking daily Aloe barbardensis Miller juice (ABMJ) for thyroid-unrelated reasons, she noticed a decrease in serum thyroperoxidase autoantibodies (TPOAb) and thyrotropin (TSH) and an increase in serum free thyroxine (FT4). Based on this observation, we enrolled 30 consecutive HT women with levothyroxine-untreated SCH and high TPOAb levels. All of them took ABMJ (50 ml daily) for nine months and were tested for serum TSH, FT4, free triiodothyronine (FT3) and TPOAb. Measurements were performed at baseline and at months 3 and 9. TSH, FT4 and TPOAb improved significantly already at month 3 and further (−61%, +23% and −56%) at month 9. However, FT3 decreased significantly at month 3 (−16%) with no further decrease at month 9, so that the FT4:FT3 ratio increased significantly (+33% and + 49%). At baseline, 100% of women had TSH > 4.0 mU/L and TPOAb > 400 U/ml, but frequencies fell to 0% and 37%, respectively, at month 9. In contrast, a control group (namely, 15 untreated SCH women of comparable age and baseline levels of TSH, FT4, FT3 and TPOAb) had no significant changes in any index. We conclude that the daily intake of 100 ml ABMJ for 9 months in women with HT-related SCH decreases the burden of thyroid autoimmune inflammation. In addition, ABMJ rescues thyrocyte function, with decreased need for conversion of the prohormone T4 into the more active T3 through ABMJ-induced inhibition of T4 deiodination.

Autoimmune Abnormalities of Postpartum Thyroid Diseases.

The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT) and the minority by Graves’ disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb), though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium) or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels) of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid.

Thyroid Function in Rett Syndrome

Introduction: Thyroid function in Rett syndrome (RTT) has rarely been studied with unanimous results. However, this aspect is of great concern regarding the effect thyroid hormones (TH) have on proper mammalian brain development. Objective: To evaluate the prevalence of abnormalities of thyroid function in a cohort of children with RTT. Patients and Methods: Forty-five consecutive Caucasian girls (mean age: 8.6 ± 5.3 years, range: 2.0-26.1) meeting the clinical criteria for RTT were recruited. In all of the subjects, we evaluated the serum concentrations of free-T₃ (FT₃), free-T₄ (FT₄), thyroid-stimulating hormone (TSH), thyroperoxidase autoantibodies, thyroglobulin autoantibodies (TgA), and TSH receptor (TSHr) autoantibodies. The results were compared with a group of 146 age-matched healthy Caucasian children and adolescent girls (median age: 9.5 years, range: 1.8-14.6) from the same geographical area. Results: Mean FT₃ and TSH levels were not significantly different between the RTT patients and controls. Nevertheless, FT₄ levels were significantly higher in RTT patients than in controls (p < 0.005). In particular, 17.7% showed FT₄ levels higher than the upper reference limit (vs. 0.7% of controls, p < 0.0001), whereas 12 patients (26.7%) showed higher FT₃ levels than the upper reference limit, significantly differing in respect to controls (2.0%, p < 0.0001). Finally, 5 patients (11.1%) showed higher levels of TSH, statistically differing from the control subjects (2.0%, p < 0.0001). However, evaluating the patients on the basis of different RTT genotype subgroups, patients with CDKL5 deletions showed significantly higher FT₄ values than patients with MeCP2 deletions (p < 0.05). On the other hand, patients with other types of MeCP2 mutations also showed FT₄ levels significantly higher than patients with MeCP2 deletions (p < 0.05). In fact, out of 8 patients with FT₄ levels higher than the upper references limit, 3 of them presented with CDKL5 deletions (3 patients, 37.5%), 4 (50%) had MeCP2 mutations, and 1 (12.5%) belonged to the subgroup of MeCP2 deletions. However, when analyzing FT₃ levels of the 12 patients showing higher FT₃ levels than the upper references limit, 6 (50%) belonged to the subgroup with MeCP2 mutations, 4 (33.3%) to the subgroup with MeCP2 deletions, and 2 (16.7%) to the subgroups with CDKL5 deletions. Furthermore, no patient with RTT was positive for antithyroglobulin autoantibodies, antithyroid peroxidase, or anti-TSHr, with no statistical differences in respect to the controls. <smlcap>L</smlcap>-thyroxine treatment was not necessary for any patient. Conclusions: Abnormalities of thyroid function are not rare in RTT. The possible relationship between these disorders and the RTT phenotype should be confirmed and studied. Children with RTT should be screened for potential thyroid dysfunction.

The role of serum C-reactive protein measured by high-sensitive method in thyroid disease.

The aim of this study was the evaluation of serum C-reactive protein (CRP) concentration as a marker of the inflammatory state in many different thyroid diseases and its dependence on the stage and duration of disease. We conducted a retrospective analysis of 444 randomly selected patients with different kinds of thyroid disease (106 men and 338 women, ranging 18–72 years of age; mean 56.2 ± 5.0 years; median 52 years). Group 1 (G1) comprised 250 patients with hyperthyroidism. Group 2 (G2) consisted of 72 euthyroid patients. Group 3 (G3) consisted of 122 patients with hypothyroidism. Free T4, free T3, and thyrotropin (TSH) levels were measured using the electrochemiluminescent method. Human serum thyroglobulin autoantibodies (Tg-Abs), thyroperoxidase autoantibodies (TPO-Abs), and autoantibodies against the thyrotropin receptor (TSHR-Abs) levels were measured by radioimmunoassay. The high-sensitive CRP (Hs-CRP) level (reference range <3 mg/L) was determined with a highly sensitive latex-based immunoassay. The mean value of Hs-CRP in G1 was 3.6 ± 2.8 mg/L, in G2 2.5 ± 1.5 mg/L and in G3 5.9 ± 5.8 mg/L. Hs-CRP (in mg/L) medians, interquartile and the total ranges in G1 were 3.0 (2.0 [0.1–21.0] 4.0); in G2: 2.3 [1.8 (0.2–9.2) 3.2]; and in G3: 4.3 [2.2 (0.3–31.5) 7.8]. We found statistically significant differences (Kruskal–Wallis test) in serum Hs-CRP values between G1 and G2 (P = 0.007), G1 and G3 (P = 0.001), G2 and G3 (P < 0.001). In G1, statistically significant correlation was confirmed between Hs-CRP and Tg-Abs (r = −0.22, P = 0.0016), CRP and TPO-Abs (r = −0.26, P < 0.001), and also between Hs-CRP and TSHR-Abs (r = −0.18, P = 0.02). In the remaining cases, differences between Hs-CRP and TSH levels (r = −0.09, P = 0.16) were not statistically significant. In G2, no statistically significant correlation was observed: Hs-CRP and Tg-Abs (r = −0.18, P = 0.13), Hs-CRP and TPO-Abs (r = −0.17, P = 0.15), Hs-CRP and TSH (r = 0.01, P = 0.91), Hs-CRP and TSHR-Abs (r = −0.19, P = 0.17). In G3, a statistically significant correlation was confirmed between Hs-CRP and Tg-Abs (r = 0.22, P = 0.012), Hs-CRP and TSH (r = −0.28, P = 0.001). No statistically significant correlation was observed between Hs-CRP and TPO-Abs (r = 0.20, P = 0.06) and between Hs-CRP and TSHR-Abs (r = −0.23, P = 0.11). Hs-CRP is increased in various types of hypothyroidism. This is particularly relevant in postpartum thyroiditis and in patients after radioiodine treatment. The impact of this situation on human health requires further research, however, one might assume that some types of thyroid disease may lead to systemic inflammatory reactions that are reflected in elevated CRP levels.

Hormonal contraception with progestagen desogestrel in women with diffuse non-toxic goiter аnd autoimmune thyroiditis

The article represents influence of gestagen desogestrel on size and function of thyroid gland in women of reproductive age. Into the study we included 70 women who were prescribed gestagen desogestrel in a daily dose of 75 mg for a period of 12 months. All the patients were devided into two groups. The first group consisted of 20 women with diffuse nontoxic goiter, the second consisted of 30 women with autoimmune thyroiditis. Control group consisted of 20 women without thyroid gland pathology. Prior to therapy with desogestrel and after 12 month of treatment, serum levels of free triiodothyronine, free thyroxine and thyrotropin releasing hormone, thyroperoxidase antibodies were determined and thyroid gland sonigraphy was performed in all the patients. Obtained data show that gestagen desogestrel doesn’t influence the size and function of thyroid gland in healthy women and in patients with diffuse non-toxic goiter. In women with autoimmune thyroiditis implication of desogestrel significantly decreases blood levels of thyroperoxidase autoantibodies.

Thyroid volume, goiter prevalence, and selenium levels in an iodine-sufficient area: a cross-sectional study

BackgroundSelenium (Se) is a necessary element for the biosynthesis of thyroid hormones. We investigated the relationship between selenium status, thyroid volume, and goiter in a cross-sectional study in an iodine-sufficient area.MethodsWe selected residents of Chengdu (over 18 years old and living in the city for more than 5 years) using a stratified cluster sampling technique. Fifteen hundred subjects were selected for the study, which involved a questionnaire survey, physical examination, thyroid ultrasound, serum thyroid function test, and determination of serum selenium level. Thyroid volume was calculated from the thickness, width, length, and a corrective factor for each lobe. Ultimately, 1,205 subjects completed the investigation and were included in our study. Additionally, 80 school-age children were selected to provide urine samples for urinary iodine analysis. We analyzed the data using appropriate nonparametric and parametric statistical tests.ResultsThe median urinary iodine value was 184 μg/L in school-age children, indicating iodine sufficiency. The median serum selenium level of the 1,205 subjects was 52.63 (interquartile range [IQR] : 40.40-67.00) μg/L. The median thyroid volume was 9.93 (IQR: 7.71-12.57) mL; both log-transformed serum selenium and log-transformed thyroid volume were Gaussian distributions (P = .638 and P = .046, respectively). The prevalences of goiter and thyroid nodules were 8.8% and 18.6%. The prevalences of positive thyroid autoantibodies, thyroperoxidase autoantibodies and thyroglobulin autoantibodies were 16.7%, 12.0%, and 11.1%, respectively. In the general linear regression model, there were positive associations between serum selenium and age, and body mass index. We found no association between serum selenium and thyroid-stimulating hormone. In simple linear regression analyses, we found no association between thyroid volume and serum selenium. There were no significant differences in serum selenium between persons with or without goiter. Serum selenium was not a risk factor for goiter.ConclusionIn our study population, serum selenium was neither associated with thyroid volume nor with goiter in an iodine-sufficient area. More studies should be conducted by following non-goitrous persons over time and monitoring their selenium status.

Iodine Contributes to Thyroid Autoimmunity in Humans by Unmasking a Cryptic Epitope on Thyroglobulin

The mechanisms linking thyroid autoimmunity and iodine use in humans are unknown. Our aim was to correlate iodine intake, thyroid autoimmunity, and recognition of thyroglobulin (Tg) epitopes after implementation of iodine prophylaxis. The general community living in an Italian village was evaluated. Thyroglobulin autoantibodies (TgAb), thyroperoxidase autoantibodies (TPOAb), and urinary iodine excretion were assessed in 906 iodized salt users (IS-users) and 389 nonusers (IS-nonusers). Ultrasound (US) was performed to identify thyroid hypoechogenicity, suggestive of Hashimoto thyroiditis (HT). TgAb epitope pattern in 16 IS-users and 17 IS-nonusers was evaluated by an inhibition binding assay to Tg, using human monoclonal TgAb-Fab directed to A, B, C, and D epitopes on Tg. Median urinary iodine excretion was slightly higher in IS-users than in IS-nonusers (112.0 μg/L vs 86.5 μg/L; P < .01). TgAb, and not TPOAb, was more frequent in IS-users (18.9% vs 13.6%, P = .02). HT-US was found in 87 subjects, among whom both positive TgAb (58.4% vs 31.8%, P = .03) and TPOAb (61.5% vs 45.4%. P = .04) were more frequent in IS-users. In this group significantly higher serum levels of TgAb (median 108 U/mL vs 30 U/mL; P = .02), but not of TPOAb, were present. Iodized salt use had no effect on the 1208 non HT-US subjects. TgAb directed to the epitope B of Tg were more frequent in IS-users than in IS-nonusers (27.5% vs 3.0%, P = .047). Iodine-induced thyroid autoimmunity is related to TgAb and the unmasking of a cryptic epitope on Tg contributes to this relationship in humans.

Chorea, convulsive seizures and cognitive impairment in a patient with autoimmune thyroid disease

Chorea and convulsive seizures are rare consequences of hyperthyroidism [1, 2]. We describe the case of such manifestation of autoimmune thyroid disease. In 2003, a 23-year-old woman presented with the first symptoms of hyperthyroidism—palpitations, weight loss and exercise intolerance. TSH and fT4 concentrations were 0.01 μIU/ml and 43 pmol/l, respectively (norm: TSH 0.35–4.9 μIU/ml, fT4 11.5–23.2 pmol/l). The patient was treated with thiamazole in tapering doses (from 60 to 10 mg per day). After 2 months, hypothyreosis was observed and thiamazole was withdrawn. 2 weeks later, the signs of thyrotoxicosis and involuntary movements of the left extremities appeared. Hyperthyreosis was verified (fT4 87.3 pmol/l) and treatment with propylothiouracil (600 mg per day) was initiated. Neurological examination confirmed left-sided hemichorea. Elevated levels of TSH receptor antibodies (TRAb) and thyroperoxidase autoantibodies (TPO Ab) were documented: 16.7 and 257.5 IU/ml, respectively (norm: 0.1–1.22 IU/ml and <60 IU/ml, respectively). Biopsy specimen of the thyroid showed lymphocytic infiltration, typical of lymphocytic thyroiditis. The patient had no family history of neurological disorders or dementia syndromes. Ceruloplasmin and copper concentrations were normal, similar to anticardiolipin, antistreptolysin O, and anti-neutrophil cytoplasm antibodies. Antinuclear and anti-double-stranded DNA antibodies were negative. Cerebrospinal fluid examination and MRI of the brain were normal, and borreliosis and toxoplasmosis were ruled out based on immunological examination of serum and cerebrospinal fluid. EEG revealed slight changes in the posterior temporal and occipital leads: theta waves and isolated sharp waves, predominantly in the right hemisphere, along with slight changes of paroxysmal character in the frontal and anterior temporal leads. Haloperidol (6 mg per day) and thioridazin (50 mg per day) were administered. fT4 concentrations diminished (28.7 pmol/l) and choreic movements considerably subsided. Treatment with a maintenance dose of thiamazole was continued. Prednisone (60 mg per day, with 5 mg reduction every week) was administered. The dosages of neuroleptics were reduced and finally withdrawn. Choreic movements diminished gradually to disappear completely within 6 weeks. The return of chorea has not been observed so far. For over a year, during treatment with thiamazole (2.5 mg per day), the patient was euthyroid. In October 2005, in the first trimester of pregnancy, symptoms of thyreotoxicosis were once again reported. TSH and fT4 concentrations were 0.02 μIU/ml and 51.73 pmol/l, respectively. Thiamazole was withdrawn and propylothiouracil (initially 150 mg per day) was administered. It was withdrawn in the third trimester, when serum fT4 decreased to 14.7 pmol/l. 3 months after the delivery, signs of hyperthyreosis were observed (fT4 = 41.7 pmol/l), and treatment with propylothiouracil (150 mg/day) was reinstated. In October 2006, the patient presented with generalized tonic–clonic convulsive seizures, loss of consciousness and retrograde amnesia. fT3 and fT4 concentrations were elevated (20.11 pg/ml and 5.19 ng/dl, respectively; norm: 1.71–3.71 pg/ml and 0.71–1.85 ng/dl, respectively). Laboratory tests and MRI of the brain were normal. Antithyroid treatment was intensified and the patient became euthyroid in December 2006. TPO Ab and anti-thyroglobulin antibodies (Tg Ab) were elevated (872.7 and 194.8 IU/ml, respectively; norm <60 IU/ml). In June 2008, the patient underwent treatment with radioactive iodine 131I (150 MBq). Between January 2009 and August 2010, the patient was euthyroid and did not receive any pharmacotherapy. During this period of time, she started to suffer from depression, difficulties with her memory, and sleep disturbances. Psychological examination confirmed mild cognitive impairment and mood disorder. Single-photon emission computed tomography of the brain showed slight global hypoperfusion in both cerebral hemispheres, and an unilateral reduction in the regional blood flow of the left parietal lobe, left temporal lobe and left insula. MRI of the brain was normal. EEG revealed slight changes in frontal and temporal leads in the form of theta waves and isolated sharp waves, accompanied by minor paroxysmal features observed in the posterior temporal and occipital leads. In January 2010, levels of TPO Ab were still elevated (324 IU/ml), while TG Ab and TRAb were normal. In August 2010, subclinical hypothyreosis was diagnosed (TSH 6.13 μIU/ml, fT4 1.36 ng/dl) and treatment with l-thyroxin (25 μg/day) was initiated. Cognitive function deterioration has not been observed thus far. The pathophysiological mechanism underlying hyperthyroidism-induced chorea is unclear. In most reported cases, choreoathetosis was observed during thyreotoxic states, and one cannot exclude autoimmune mechanisms underlying the chorea [2, 3]. Morphological changes in the basal ganglia are another potential cause of chorea in patients with hyperthyroidism [3]. Seizures are one of the clinical features of encephalopathy associated with autoimmune thyroiditis, often termed Hashimoto’s encephalopathy. The exact pathomechanism of this disease is still not fully understood. Its neurological symptoms can result from autoimmune inflammation of minute cerebral vessels, with the involvement of anti-TPO antibodies [4]. Hereby, presented case illustrates that cognitive impairment may be an unusual consequence of autoimmune thyroid disease, and thyroid function should be examined in subjects with encephalopathy, chorea and seizures.

Number of autoantibodies and HLA genotype, more than high titers of glutamic acid decarboxylase autoantibodies, predict insulin dependence in latent autoimmune diabetes of adults

In latent autoimmune diabetes of adults (LADA), the progression into insulin-dependent diabetes is usually faster than in type 2 diabetes (T2D) but the factors influencing this progression are not completely known. In this study, we searched for sensitive markers associated with early development of insulin dependence. The screening of 5568 T2D patients for glutamic acid decarboxylase autoantibodies (GAD65Ab) identified 276 LADA patients (M=131; F=145) and in 251 of them, tyrosine phosphatase-2 (IA-2Ab) and thyroperoxidase autoantibodies (TPOAbs), some clinical features and genotype variation of the main type 1 diabetes (T1D) disease susceptibility loci (HLA-DRB1 and HLA-DQB1) were analyzed. Four years after the diagnosis of diabetes, high GAD65Ab titer was not significantly associated with faster progression toward insulin deficiency (P=0.104). Patients with GAD65Ab and TPOAb or IA-2Ab or triple positivity for both islet and TPOAbs (GAD65Ab/IA-2Ab/TPOAb) showed a significantly faster disease progression (P=0.002). Among 104 TPOAb-positive LADA patients, 10 received replacement therapy (l-thyroxine), 43 showed high TSH levels (62.7% developed insulin dependence), and 3 had hyperthyroidism treated with methimazole. Multivariate analysis revealed a significant effect on disease progression only for TPOAb (P=0.022), female gender (P=0.036), low body mass index (BMI; P=0.001), and T1D high/intermediate risk HLA-DRB1/DQB1 genotypes grouped (P=0.020). High GAD65Ab titers per se are not a major risk factor for disease progression in LADA, while the number of positive autoantibodies and HLA DRB1-DQB1 genotypes at high risk for T1D are significant predictors. Moreover, clinical characteristics such as low BMI and female gender are more likely to identify patients who will require insulin therapy within 4 years of diagnosis.

Serum thyroid autoantibodies in patients with idiopathic either acute or chronic urticaria

In Italy, only one study was conducted on the detection of serum thyroid autoantibodies (ATA) in patients with urticaria. This northern-Italy study reported a 23% rate of ATA positiveness in 52 patients with chronic idiopathic urticaria (CIU). During the years 1998-2006, 688 patients with urticaria were hospitalized at our Division of Allergy and Clinical Immunology. Thyroglobulin and thyroperoxidase autoantibodies (TgAb and TPOAb) were assayed at admission in 144/688 patients. Of the 144 patients (mean age: 42.3+/-15.8 yr, range 17-84), 95 (72 women and 23 men) had an history of CIU (CIU group) and 49 (44 women and 5 men) did not [acute urticaria group or (AU)]. Of the 144 patients, 37 (25.7%) tested positive for at least one ATA: 31 with CIU (32.6%) and 6 with AU (12.2%, chi2=7.037, p=0.008). Positiveness for TPOAb or TgAb was 30/37 (81.1%) or 17/37 (45.9%); 10/37 (27.0%). Pre-hospitalization duration of CIU was longer in the 31 ATA positive patients compared to the 64 ATA negative patients (207.2+/-273.4 vs 81.6+/-106.3 weeks, p=0.015). Pre-hospitalization duration of CIU correlated positively with the log10-transformed serum concentration of TPOAb in the 25 CIU patients who tested TPOAb positive (r=0.42, p=0.039). We conclude that our rate of 31/95 (32.6%) positiveness for at least one type of ATA in CIU is greater than that of 6 representative international studies published between the years 2000 and 2006 (111/488 or 22.7%, range 15-29%, chi2=4.884, p=0.027).

Antithyroperoxidase Antibody-Dependent Cytotoxicity in Autoimmune Thyroid Disease

Thyroid antibody-dependent cytotoxicity has been reported in autoimmune thyroid disease (AITD). Indeed, the role of thyroperoxidase (TPO) autoantibodies (aAbs) in complement-mediated damage by binding to TPO expressed on the surface of human thyroid cells was demonstrated, whereas their activity in antibody-dependent cell cytotoxicity (ADCC) is not well established. The aim of this study was to define the partners involved in antibody and complement-dependent cytotoxicity (CDC) in AITD and characterize which effector cells are involved in cytotoxicity mediated by anti-TPO aAbs using a chromium release assay. The relative capability of anti-TPO aAbs to mediate ADCC using human thyroid cells in culture varies from 11 to 74.5%, depending on the effectors cells used. The human monocyte cell line HL60 gives a better lysis than the THP-1 cell line as effector cells. It seems obvious that the mechanism of ADCC is mediated quite exclusively by FcgammaRI. Indeed, the two effector cell lines differ by the level of the FcgammaRI expression (91.83% for HL-60 cells and 22.55%t for the THP-1). In addition to ADCC, the anti-TPO aAbs mediate the destruction of thyrocytes by CDC (56%). These results demonstrate that anti-TPO aAbs can damage cultured thyroid cells by ADCC and CDC mechanisms. The monocytes, via their FcgammaRI, are important effector cells in ADCC mediated by anti-TPO aAbs and may contribute with T cells to the destruction of thyroid gland in AITD.

Increased Prevalence of Thyroid Autoimmunity and Hypothyroidism in Patients with Glycogen Storage Disease Type I

To investigate the hypothalamus-pituitary-thyroid axis in patients with glycogen storage disease type 1(GSD1). Ten patients with GSD1a, 7 patients with GSD1b, and 34 sex- and age-matched healthy control subjects were enrolled in the study. The levels of serum-free thyroxine (FT4) were significantly lower in patients with GSD1a and GSD1b (P < .05), whereas thyrotropin was significantly higher compared with control subjects only in patients with GSD1b (P < .005). Thyroglobulin and thyroperoxidase auto-antibodies were significantly higher in patients with GSD1b than in patients with GSD1a and control subjects (P < .005). After thyrotropin-releasing hormone stimulation, an enhanced thyrotropin response was found in patients with GSD1a and patients with GSD1b (P < .005) compared with control subjects. The presence of a subclinical or overt hypothyroidism was found in 4 of 7 patients with GSD1b and in no patient with GSD1a (chi2 = 7.47, P < .005) or control subject (chi2 = 27.2, P < .0001). Patients with GSD1b have an increased prevalence of thyroid autoimmunity and hypothyroidism, although patients with GSD1a have little evidence of thyroid abnormalities. Concomitant damage at the level of the hypothalamus or pituitary gland might be hypothesized on the basis of the slightly elevated thyrotropin levels, even in patients with overt hypothyroidism.