Non-autoimmune Thyroid Disease Research Articles

Postoperative complications after total thyroidectomy for benign thyroid diseases

Background: The thyroid gland is normally impalpable, once enlarged it is called goiter which may be simple, toxic, inflammatory or neoplastic. Autoimmune thyroid disease (ATD) includes goiters associated with antigen antibody reaction that initiates a series of inflammatory reactions. Due to these inflammatory reactions surgeries become more difficult with a tendency to develop postoperative complications.Methods: This is a prospective study on 207 patients with thyroid disorders who were treated with total thyroidectomy in general surgery department, Menoufia university hospital between October 2015 and December 2018. Patients were divided into two groups based on postoperative histopathological findings group A included 73 patients with autoimmune thyroid disease while group B included 134 patients with non-autoimmune thyroid disease. All patients were followed up for 6 months postoperatively to evaluate vocal cord palsy and hypoparathyroidism.Results: In our study, the rate of temporary and permanent vocal cord palsies were 4.1% and 1.4% in ATD group respectively while in non-ATD group were 1.5% and 0.7% respectively with no statistically significant difference between both groups, whereas the rate of temporary and permanent hypoparathyroidism were 9.5% and 4.1% in ATD group respectively while in non-ATD group were 2.9% and 0.7% respectively with significantly higher rate in ATD group.Conclusions: Surgery for ATD is a challenging procedure but safe with a low incidence of general complications and vocal cord palsy when compared with surgery for non-ATD. However, postoperative hypoparathyroidism is significantly higher due to dense adhesions which obscure the surgical field so a special attention should be paid to the parathyroid glands during total thyroidectomy.

Phenotypic Expression of Autoimmunity in Children With Autoimmune Thyroid Disorders.

Autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), tend to aggregate with other non-thyroidal autoimmune diseases (NTADs). Aim of this Mini-review is to report the most recent insights concerning the clustering of NTADs in pediatric patients with either HT or GD, the pathophysiology of AITDs and the metamorphic thyroid autoimmunity. A systematic literature research of the last 15 years, according to EQUATOR statement, was carried out through MEDLINE via PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) Embase, CINAHL, Cochrane Library, based on the following keywords: (autoimmune thyroid disease OR Hashimoto thyroiditis OR Grave's disease) AND (autoimmune comorbidities OR extra-thyroidal autoimmune disorders) AND (children OR adolescents OR pediatrics) AND (celiac disease OR type 1 diabetes mellitus OR arthropathies OR cutaneous diseases) AND (Turner syndrome OR Down syndrome). One-hundred and twenty-eight manuscripts were extrapolated but only seventeen were eligible. On the basis of the available reports it may be inferred that clustering of NTADs can be significantly modified by both patients' age at AITDs presentation and association with Down's syndrome (DS). Particularly, the association of AITDs with celiac disease and type 1 diabetes was most commonly reported in children than in adults. A sequential shifting from HT to GD has been described in children with AITDs, and it seems to be more frequent in children with DS than in those without DS. Coexistence of autoimmune diseases might be the result of a complex interaction among genetics, environment and epigenetic modifications that are able to affect gene expression, immune system response and, finally, the pathogenesis of autoimmune diseases.

MON-596 Male Individuals with Autoimmune Thyroid Disease Present Higher Risk for Clustering Other Non-Thyroidal Autoimmune Diseases

Background: Autoimmune thyroid disease (ATD) share common pathophysiology pathways with several other autoimmune diseases. It can be a first manifestation of an immunoregulatory diathesis, leading to a cluster of associated autoimmunities. Aim: The present study aimed to evaluate and compare the frequency of Type 1 diabetes (T1DM) and celiac disease (CD) related antibodies among pediatric and adult patients with Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). Methods: A total of 145 individuals, aged 2 to 50 years (114 females; 89 pediatric patients) were included in a cross-sectional descriptive study (74 HT). Determination of antibodies related to T1DM (GADA65 and IA2), CD (tTG-IgA and EMA-IgA) and Anti-Saccharomyces Cerevisiae (ASCA) were performed. Results: Non-thyroidal autoimmune diseases (NTAID) was found in 8.3% of individuals. Males presented a 3.2-time higher risk for a second NTAID (p=0.004) and a 4-time higher risk for a third NTAID (p=0.017). The pediatric group had 53% higher risk for developing a second NTAID (p=0.042). GADA65, IA2 and ASCA-IgG positivity were found in 11%, 2.7% and 14.4% of the individuals, respectively. CD-related antibodies were found in a ratio of 1:48 patients. Conclusion: Individuals with ATD present high rates of T1DM and CD-related antibodies. The male group, regardless of age, has a higher rate of CD-related antibodies and also higher risk for developing two or more NTAIDs. The pediatric population with ATD presents a higher rate of AID clustering than adults. A closer surveillance for associated NTAID throughout follow-up should be performed, mainly in young male group.

MON-616 Potential Relationship between Hypothyroidism and Periodontal Disease Severity

Introduction: Hypothyroidism is an endocrine disorder having autoimmune and inflammatory etiologies. There is evidence that periodontal disease might be influenced by a variety of systemic inflammatory conditions in a bidirectional manner, including diabetes, cardiovascular disease, adverse pregnancy outcomes, and osteoporosis.1 Consequently, we hypothesized that the severity of periodontitis also might be influenced by hypothyroidism. Methods: IRB approval was obtained prior to initiation of this study. To test our hypothesis, records of patients referred to a faculty periodontal practice during the 20-year period from 1996-2015 were reviewed (N=1093). Inclusion criteria included the presence of chronic, generalized moderate-to-severe periodontitis (stage III to IV; grade B to C).2 Exclusion criteria were diabetes, smoking, systemic steroids, hormonal supplementation unrelated to thyroid disease, and non-thyroid autoimmune disease. After applying those criteria, 538 patients were considered for further analysis. Periodontal disease severity was measured by calculating the percent of teeth with probing depths ≥5 mm or ≥6 mm. The presence of hypothyroidism was determined by review of patient medical history for use of prescription medication(s) for thyroid hormone supplementation. Significance was measured via analysis of variance and independent sample t-tests calculated using IBM SPSS Statistics v25. Results: Patients with hypothyroidism had more teeth with greater probing depths, implying more severe periodontal disease. Specifically, 61.4% of teeth from periodontitis patients with hypothyroidism had periodontal probing depths ≥5 mm, vs. 48.1% of teeth in periodontitis patients without hypothyroidism (27.7% increase, mean difference= 13.3%, 95% confidence interval= 7.9%-18.8%, P=5E-06). Similarly, the prevalence of probing depths ≥6 mm was 36.2% in periodontitis patients with hypothyroidism, vs. 28.2% for periodontitis patients without hypothyroidism (28.4% increase, mean difference= 8.0%, 95% confidence interval= 3.1%-12.9%, P=0.002). Conclusions: Our data indicate that the prevalence of moderate to advanced periodontitis might be influenced by hypothyroidism. Prospective and retrospective studies are currently underway to determine whether hypothyroidism might be associated with systemic or inflammatory changes that might affect periodontal disease progression. Studies measuring the relationship of hypothyroidism on less severe forms of periodontitis also are in progress. Collectively, our data suggest that periodontists should consider thyroid disease, and endocrinologists should consider clinical history or signs of periodontal disease, as a component of patient evaluation.

Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer

BackgroundThyroid cancer and thyroid autoimmunity are considered opposite extremes of immune-responses. However, several studies have suggested that thyroid cancer coexists with autoimmune thyroid diseases like Hashimoto Thyroiditis (HT) and Graves disease (GD). We have shown that the risk of developing thyroid cancer is higher in patients with a silent form of autoimmune thyroid disease -Euthyroid Hashimoto Thyroiditis-(EHT).MethodsWe analyzed data from 2633 consecutive patients with GD, HT, EHT and non-Autoimmune Thyroid Disease (Non-AITD) for the presence of Differentiated Thyroid Cancer (DTC). We further investigated the microenvironment, and cellular mechanism of protection from DTC in GD/EHT by ex-vivo aspirating infiltrates from thyroid samples. We also re-constituted in vitro the in-vivo microenvironment to mimic an in-vivo context. We isolated NK cells and differentiated macrophages into M1 and M2 phenotype from healthy human peripheral blood monocytes.ResultsDTC was less frequent/aggressive in GD as compared to EHT or Non-AITD. Intra-thyroidal immune-cell profiling revealed differential Natural Killer (NK) cell activity and macrophage polarization in the settings of GD versus EHT. In GD, NK-cells were activated, and macrophages showed M1-like phenotype whereas, in EHT, NK-cells were less active and macrophages displayed M2-like phenotype. Furthermore, in vitro co-cultures of NK-cells with differentiated macrophage subsets revealed that the presence of activated NK (NA) cells favors M1 macrophages, boosts macrophage action and amplifies the innate defense mechanisms. Moreover, co-culture of M2 macrophages with NA, increases the cytotoxicity of NK-cells and favors a pro-inflammatory microenvironment that reverts the anti-inflammatory M2 towards pro-inflammatory M1.ConclusionSurveillance innate immune-cells like Natural Killer (NK) cells and macrophages are complementary to each other in their actions. We discovered here that activated NK-cells in the background of the thyroid autoimmune disease, GD, drive macrophage differentiation to the M1/killer phenotype which in turn is cytotoxic to cancer cells and down regulates the M2/repair phenotype. Understanding the molecular basis of macrophage-NK cell interface in Thyroid Cancer, ETH and GD will open new vistas for immunopathology and therapeutic intervention. Macrophages/innate immunity can be modulated from M2 to M1 phenotype to help treat thyroid cancer as naturally done by GD.

A novel third-generation TSH receptor antibody (TRAb) enzyme-linked immunosorbent assay based on a murine monoclonal TSH receptor-binding antibody

TSH receptor (TSHR) autoantibody (TRAb) is the serological hallmark of Graves’ disease (GD). Third-generation enzyme-linked immunosorbent assays (ELISAs) using monoclonal TRAbs instead of TSH have been found useful for TRAb analysis recently. For the first time, a mouse monoclonal antibody (mAb) against TSHR was analyzed for TRAb detection and compared with human mAb M22 and TSH by the same competitive binding assay technique. A mouse monoclonal antibody (T7) binding to the TSH receptor and inhibiting TSH binding was generated and used for TRAb analysis in a third-generation ELISA. Obtained TRAb levels were compared with a second-generation TRAb assay employing bovine TSH and a third-generation assay with human mAb M22 as TSHR-binding reagents by investigating 89 patients with GD, 56 with Hashimoto’s thyroiditis (HT), 73 with non-autoimmune thyroid diseases, 17 with rheumatoid arthritis, and 100 healthy subjects. The T7-based TRAb ELISA did not reveal a significantly different assay performance (area under the curve [AUC]) in contrast to the TSH and M22-based TRAb ELISAs by receiver operating characteristic (ROC) curve analysis (AUC-T7 0.967, AUC-TSH 0.972, AUC-M22 0.958, p > 0.05, respectively). After adjustment of cutoffs by ROC, all three TRAb ELISAs demonstrated sensitivities and specificities above 89.9% and 96.0%, respectively. Both third-generation TRAb ELISAs showed a tendency for a higher prevalence of TRAb positives in HT in contrast to the second-generation ELISA. Mouse mAbs against the TSHR may be used for the reliable detection of TRAb by third-generation TRAb ELISA. The earlier reported higher sensitivity of third-generation TRAb ELISA in GD needs to be considered in the context of a slightly lower specificity regarding HT.

Patients with Benign Thyroid Diseases Experience an Impaired Sex Life.

This study aimed to characterize the frequency of self-reported thyroid-related impaired sex life in patients with thyroid diseases, to examine its clinical correlates and relationship with overall quality of life (QOL), and to investigate the effect of treatment. Two separate patient samples with benign thyroid diseases were investigated: a cross-sectional sample (759 women and 118 men) treated at two Danish university hospital outpatient clinics, in 2007-2008, and a longitudinal sample (358 women and 74 men) undergoing treatment at the abovementioned centers, during 2008-2012, evaluated before and 6 months after therapy. The thyroid-specific QOL questionnaire ThyPRO was used to measure patient-evaluated thyroid-related sex life impairment. Biochemical and clinical variables were analyzed (i.e., age, education, degree of thyroid dysfunction, comorbidity, serum thyrotropin, total thyroxine, and triiodothyronine, as well as thyroperoxidase and thyrotropin receptor antibody concentrations). The SF-36 Health Survey was used to analyze the effect of impaired sex life on overall QOL. In the cross-sectional sample, 36% of women and 31% of men reported what they perceived to be thyroid-attributable impaired sex life. Women with autoimmune thyroid diseases reported more impairment than those with non-autoimmune thyroid diseases. In patients with Graves' disease lower levels of educational attainment and in patients with toxic nodular goiter comorbidities were associated with impaired sex life. Overall QOL was lower in patients with thyroid-related sex life impairment. In the longitudinal sample, 42% of women and 33% of men had impaired sex life at baseline, which improved at 6 months follow-up only in women and, when analyzing individual diagnoses separately, statistically significantly among those with autoimmune hypothyroidism. Sexual impairment was associated with low education in patients with toxic nodular goiter and with high plasma triiodothyronine concentrations in patients with Graves' disease. In autoimmune hypothyroidism, a younger age was associated with sex life impairment. We found a high frequency of self-reported, thyroid-related sex life impairment in patients with benign thyroid diseases, especially in young women with autoimmune thyroid diseases. Self-perceived impaired sex life persisted in women treated for Graves' disease, suggesting that normalization of thyroid function was not sufficient to restore sexual function.

Thyroid peroxidase antibody-positivity, but not isolated thyroglobulin antibody-positivity, is associated with non-thyroidal autoimmune diseases - a population study of more than 8000 Danes

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

INCREASED PREVALENCE OF NON-THYROID AUTOIMMUNE DISEASE IN PATIENTS WITH FAMILIAL FRONTOTEMPORAL DEMENTIA ASSOCIATED WITH PROGRANULIN MUTATIONS

Familial frontotemporal dementia (FTD) is most commonly due to mutations in progranulin (GRN), microtubule-associated protein tau (MAPT), or chromosome 9 open reading frame 72 (C9orf72). Recent research has observed an increased prevalence of non-thyroid autoimmune disease in ‘TDP-43-opathies’ such as GRN- and C9orf72- related FTD and motor neuron disease. To investigate this further, we analysed the prevalence of systemic autoimmune disease across a well-characterised cohort of symptomatic familial FTD patients and healthy controls. We assessed 31 patients with GRN mutations (2 with dual GRN/C9orf72 mutations), 40 with MAPT mutations, 36 with C9orf72 expansions (2 with dual C9orf72/GRN mutations and 1 with a dual C9orf72/SQSTM1 mutation) and 24 healthy controls. Presence/absence of autoimmune disease was recorded through retrospective case notes review. Autoimmune conditions were sub-classified into ‘thyroid’ or ‘non-thyroid’ disease. Presence of autoimmune disease and gender were compared between groups using Chi squared and Fisher's exact tests, with a significance threshold of p<0.05. Gender did not differ significantly between groups. Total autoimmune disease was significantly more prevalent in the total GRN mutation group than the MAPT group (35.5% vs. 7.5%; p=0.003), with a trend towards a greater prevalence when compared with controls (35.5% vs. 12.5%; p=0.052), but not compared with the total C9orf72 mutation carriers (22.2%). This was due to an increased prevalence of non-thyroid, rather than thyroid, disease in the GRN group (19.4%) compared with the MAPT group (2.5%; p=0.038) and controls (0.0%; p=0.030). The greater prevalence in the GRN group compared with the MAPT group was seen even if the dual GRN/C9orf72 mutations were excluded (31.0% vs. 7.5%; p=0.011). Prevalence of total, thyroid and non-thyroid autoimmune disease was not significantly different between other groups. FTD patients with GRN mutations have a particularly high prevalence of non-thyroid systemic autoimmune disease, confirming observations from previous studies. In this study, the prevalence in patients with C9orf72 or MAPT mutations is not different from controls, suggesting that the underlying disease mechanism may not be as closely linked to autoimmune disease. Impairment of the immune functions of GRN could cause systemic and cerebral immune dysregulation from an early age in GRN mutation carriers.

Skin findings in autoimmune and nonautoimmune thyroid disease with respect to thyroid functional status and healthy controls.

Thyroid disorders are associated with a wide variety of skin disorders that respond to treatment of hormone imbalance in most cases and thus are of vital importance to dermatologists. This study aimed to evaluate skin findings associated with autoimmune and nonautoimmune thyroid disease with respect to thyroid functional status and healthy controls. A total of 300 consecutive patients with either autoimmune (n = 173) or nonautoimmune (n = 127) thyroid disease and 100 healthy control subjects were included in this cross-sectional study. Data on patient demographics, thyroid function tests, and skin findings were recorded for patient and control groups. Compared to control subjects, patients had higher proportions in populations with alopecia (P < 0.001), nail thinning (P = 0.02), brittle nails (P = 0.001), pruritus (P < 0.001), diffuse hyperhidrosis (P = 0.01), flushing (P = 0.001), and xerosis (P < 0.001). Onycholysis (P = 0.02), yellow skin (P = 0.04), periorbital edema (P = 0.03), psoriasis (P = 0.001), and palmoplantar hyperkeratosis (P = 0.007) were significantly more common in patients with autoimmune than nonautoimmune thyroid disease. A significantly higher percentage of patients with autoimmune rather than nonautoimmune thyroid disease had overall skin findings (P = 0.03) among the hyperthyroid patients.Conclusions: Our findings indicate that the presence of skin findings in a majority of thyroid patients significantly differs for certain cutaneous manifestations with respect to controls, autoimmune etiology, and thyroid functional status.

Autoimmune comorbidities in Hashimoto's thyroiditis: different patterns of association in adulthood and childhood/adolescence.

Hashimoto's thyroiditis (HT), the most common autoimmune thyroid disease at any age, is often associated with other autoimmune diseases. The present study was aimed to describe the type and frequency of non-thyroidal autoimmune diseases (NTADs) in HT patients and to delineate the clinical pattern of diseases clustering in pediatric/adolescent and adult age. Cross-sectional study. 1053 newly diagnosed HT patients (500 adults (467 F, mean age 40.2 ± 13.7 years) and 553 children/adolescents (449 F, mean age 11.1 ± 3.0 years)) were evaluated for common NTADs by means of careful recording of medical history, physical examination and assessment of selected autoantibody profiles. The prevalence of associated NTADs was significantly higher in adults than that in pediatric/adolescent HT patients (P < .0001). In addition, the number of adult patients suffering from two or more associated NTADs was significantly higher than that of children/adolescent (P < 0.0001). A female prevalence was evident in both cohorts, but was significant in the adults (P < 0.0001). The epidemiological distribution of NTADs was strongly different in the two cohorts, the most frequent associated diseases being arthropathies and connective tissue diseases in adults and type 1 diabetes and coeliac disease in children/adolescents. Skin diseases were represented with similar prevalence in both cohorts, vitiligo being the most common. Age at HT presentation may influence autoimmune diseases clustering, favoring the association of specific NTADs in different ages of life. Moreover, the association between HT and NTADs increases with age and occurs most frequently in adults.

Increased prevalence of autoimmune disease within C9 and FTD/MND cohorts: Completing the picture.

Objective:To determine the prevalence of autoimmune disease in symptomatic C9ORF72 (C9) mutation carriers and frontotemporal dementia with motor neuron disease (FTD/MND) cohorts.Methods:In this case-control study, we reviewed the clinical histories of 66 patients with FTD/MND and 57 symptomatic C9 carriers (24 overlapping cases), a total of 99 charts, for history of autoimmune disease. The prevalence of autoimmune disease in C9 and FTD/MND cohorts was determined by χ2 and Fisher exact comparisons between the combined C9 and FTD/MND group with normal control, Alzheimer disease, and progressive supranuclear palsy cohorts, as well as comparisons within C9 and FTD/MND cohorts.Results:Our combined C9 and FTD/MND cohort has a 12% prevalence of nonthyroid autoimmune disease. The prevalence of nonthyroid autoimmune disease in C9 and FTD/MND is similar to the rates in previously detailed progranulin and semantic variant primary progressive aphasia cohorts and elevated in comparison to previously collected normal control and typical Alzheimer disease cohorts, as well as a newly screened progressive supranuclear palsy cohort. Furthermore, the types of autoimmune disease in this combined C9 and FTD/MND cohort cluster within the same 3 categories previously described in progranulin and semantic variant primary progressive aphasia: inflammatory arthritides, cutaneous conditions, and gastrointestinal disorders.Conclusions:The association between selective autoimmune disease and neurodegenerative disorders unified by the underlying pathology frontotemporal lobar degeneration with TDP-43–positive inclusions (FTLD-TDP) extends to C9 and FTD/MND cohorts, providing further evidence that select autoimmune inflammation may be intrinsically linked to FTLD-TDP pathophysiology.

Thyroid Peroxidase Antibodies in Non-Autoimmune Hyperthyroidism Treated with Radioactive Iodine.

Introduction: Earlier studies suggest increased serum levels of thyroid peroxidase antibodies (TPOAb) in some cases with non-autoimmune hyperthyroidism. The aim of the study was to assess the incidence of hypothyroidism in patients with nodular toxic goitre and toxic adenoma at 12 months after radioactive iodine therapy in the relation to TPOAb levels. Patients & Measurements: The study comprised 100 patients (83 females; 17 males) treated with radioactive iodine therapy. Serum concentrations of thyrotropin, free thyroxin, TPOAb, and anti-TSH receptor antibodies were assessed at baseline and 12 months after radioactive iodine therapy. Results: High TPOAb level (>60.0 IU/mL) was found in 27% of patients at baseline and 32% at the follow-up. Baseline TPOAb values were higher in subjects with coexisting non-thyroid autoimmune disease (p=0.041). After radioactive iodine therapy, the mean TPOAb level increased in patients with normal baseline TPOAb (p=0.03) and the rates of euthyroidism and hypothyroidism were 61 and 34%, respectively. The rate of hypothyroidism after radioactive iodine therapy was not significantly different in groups with normal and high baseline TPOAb. Conclusions: 27% of patients with non-autoimmune hyperthyroidism were positive for TPOAb. However, baseline TPOAb level did not influence the rate of hypothyroidism at 12 months after radioactive iodine therapy. Our results suggest a more close surveillance after radioactive iodine therapy of patients harboring these antibodies.

Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population

The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients.

Can desalinated seawater contribute to iodine-deficiency disorders? An observation and hypothesis.

Over 300 million people rely on desalinated seawater and the numbers are growing. Desalination removes iodine from water and could increase the risk of iodine-deficiency disorders (IDD). The present study assessed the relationship between iodine intake and thyroid function in an area reliant on desalination. A case-control study was performed between March 2012 and March 2014. Thyroid function was rigorously assessed by clinical examination, ultrasound and blood tests, including serum thyroglobulin (Tg) and autoimmune antibodies. Iodine intake and the contribution made by unfiltered tap water were estimated by FFQ. The contribution of drinking-water to iodine intake was modelled using three iodine concentrations: likely, worst-case and best-case scenario. The setting for the study was a hospital located on the southern Israeli Mediterranean coast. Adult volunteers (n 102), 21-80 years old, prospectively recruited. After screening, seventy-four participants met the inclusion criteria. Thirty-seven were euthyroid controls. Among those with thyroid dysfunction, twenty-nine were classified with non-autoimmune thyroid disease (NATD) after excluding eight cases with autoimmunity. Seventy per cent of all participants had iodine intake below the Estimated Average Requirement (EAR) of 95 µg/d. Participants with NATD were significantly more likely to have probable IDD with intake below the EAR (OR=5·2; 95 % CI 1·8, 15·2) and abnormal serum Tg>40 ng/ml (OR=5·8; 95 % CI 1·6, 20·8). Evidence of prevalent probable IDD in a population reliant on desalinated seawater supports the urgent need to probe the impact of desalinated water on thyroid health in Israel and elsewhere.

Analytical Performance and Validation of a Bioassay for Thyroid-Blocking Antibodies.

A cell-based bioassay for the measurement of thyroid blocking autoantibodies (TBAb) has been recently reported. The analytical performance and validation of this bioassay is assessed and described. Chinese hamster ovary cells expressing a chimeric thyrotropin receptor were treated with bovine (b) TSH and different concentrations of an immunoglobulin G (IgG) monoclonal human TBAb (K1-70). TBAb was measured as a function of luciferase activity relative to bTSH alone and expressed as percent inhibition. Results obtained in the chimeric cell line were compared with those of a wild-type cell line. Analytical performance studies were subsequently performed with the chimeric cell line only. Immunodepletion of K1-70 IgG by using a protein G-Sepharose column showed that positive percent inhibition in the TBAb bioassay was detectable from K1-70 IgG only. The limit of blank was determined to be 12.2%. The limit of detection was 14% inhibition, equivalent to 0.4 ng/mL K1-70, while the limit of quantitation was 22% (coefficient of variation [CV] 12%) equivalent to 0.625 ng/mL K1-70. The dynamic range was between 14 ± 3.7 (mean % inhibition ± standard deviation) and 101 ± 2.6, equivalent to 0.4-10 ng/mL K1-70. The linear range was between 22 ± 2.6 and 93 ± 0.6 inhibition, equivalent to 0.625-5 ng/mL K1-70. The upper limit of the 99th percent reference range was 34% inhibition. In two laboratories, CV values for the intra- and inter-assay precisions for K1-70 ranged from 2% to 12% and from 1.7% to 14.5%, respectively. For patient sera, the CV values for the intra- and inter-assay precisions ranged from 3% to 9% and from 3% to 11%, respectively. No interference was found when follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotrophin were tested in the TBAb bioassay. The median of % inhibition values in 40 TBAb positive sera from patients with autoimmune thyroid disease were 93.5 (range 25-103) and 92 (range 64-107) for the wild type and chimeric cell lines, respectively. Further, all 40 samples of patients with various non-thyroidal autoimmune diseases were TBAb negative. This TBAb bioassay exhibits excellent analytical performance and high level of reproducibility.

Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure.

Abnormalities in peripheral blood natural killer (NK) cells have been reported in women with primary infertility and recurrent spontaneous abortion (RSA) and several studies have been presented to define cutoff values for abnormal peripheral blood NK cell levels in this context. Elevated levels of NK cells were observed in infertile/RSA women in the presence of thyroid autoimmunity (TAI), while no studies have been carried out, to date, on NK cells in infertile/RSA women with non-autoimmune thyroid diseases. The contribution of this study is two-fold: (1) the evaluation of peripheral blood NK cell levels in a cohort of infertile/RSA women, in order to confirm related data from the literature; and (2) the assessment of NK cell levels in the presence of both TAI and subclinical hypothyroidism (SCH) in order to explore the possibility that the association between NK cells and thyroid function is not only restricted to TAI but also to SCH. In a retrospective study, 259 age-matched women (primary infertility [n = 49], primary RSA [n = 145], and secondary RSA [n = 65]) were evaluated for CD56+CD16+NK cells by flow cytometry. Women were stratified according to thyroid status: TAI, SCH, and without thyroid diseases (ET). Fertile women (n = 45) were used as controls. Infertile/RSA women showed higher mean NK cell levels than controls. The cutoff value determining the abnormal NK cell levels resulted ⩾15% in all the groups of women. Among the infertile/RSA women, SCH resulted the most frequently associated thyroid disorder while no difference resulted in the prevalence of TAI and ET women between patients and controls. A higher prevalence of women with NK cell levels ⩾15% was observed in infertile/RSA women with SCH when compared to TAI/ET women. According to our data, NK cell assessment could be used as a diagnostic tool in women with reproductive failure and we suggest that the possible association between NK cell levels and thyroid function can be described not only in the presence of TAI but also in the presence of non-autoimmune thyroid disorders.

The upper reference limit for thyroid peroxidase autoantibodies is method-dependent: A collaborative study with biomedical industries

BackgroundThe determination of the upper reference limit (URL) for thyroid peroxidase autoantibodies (TPOAbs) is a contentious issue, because of the difficulty in defining the reference population. The aim of this study was to establish the URL (eURL) for TPOAbs, according to the National Academy of Clinical Biochemistry (NACB) guidelines and to compare them with those obtained in a female counterpart, by the use of six commercial automated platforms. Methods120 healthy males and 120 healthy females with NACB-required characteristics (<30years, TSH between 0.5 and 2.0mIU/L, normal thyroid ultrasound, without personal/family history of thyroid and non-thyroid autoimmune diseases) were studied. Sera were analyzed for TPOAbs concentration using six immunoassay methods applied in automated analyzers: Advia Centaur XP (CEN), Siemens Healthcare Diagnostics; Maglumi 2000 Plus, Shenzen New Industries Biomedical Engineering; Architect ci4100, Abbott; Cobas e411 (COB) Roche Diagnostics; Unicel DxI (UNI) and Lumipulse G1200, Fujirebio. ResultsWithin each method, TPOAbs values had a high degree of dispersion and the eURLs were lower than those stated by the manufacturer. A statistically significant difference (p<0.05) between medians of males and females was observed only for COB and for UNI. However, the comparison of the male and female proportions positive for TPOAbs using the eURL of the counterpart, showed the lack of clinical significance of the above differences (Chi-square test, p>0.05). ConclusionsDespite the analytical harmonization, the wide dispersion of the results and the differences of the eURLs between methods suggest the need of further studies focusing on TPO antigen preparations as the possible source of variability between different assays. In addition, the lack of clinical significant difference between males and females, in terms of TPOAb eURLs, confirms the suitability of the NACB recommendations.

The sodium iodide symporter is unlikely to be a thyroid/breast shared antigen.

Anti-thyroid peroxidase (TPO) autoantibodies (TPOAb) seem to be protective for patients with breast cancer (BC). Thyroid and breast tissues both express the sodium iodide symporter (NIS), similarly both have a peroxidase activity, TPO and lactoperoxidase (LPO) respectively. We hypothesize a common immune response to a thyroid/breast shared antigen suggesting three putative mechanisms: (1) TPOAb react to both TPO and LPO, (2) TPO could be expressed in BC and (3) patients with TPOAb could have autoantibodies to NIS (NISAb). Previous studies excluded NISAb that block NIS activity in sera of patients with thyroid autoimmunity (TA) and/or BC. This study investigates neutral NISAb (binding without affecting function). Clones of CHO cells stably expressing human NIS (hNIS; CHO-NIS) were isolated following transfection of hNIS in pcDNA3 vector. Expression of hNIS mRNA and surface protein was confirmed by PCR and flow cytometry respectively using a hNIS-mouse-monoclonal-antibody. CHO-NIS and controls transfected with the empty pcDNA3 vector (CHO-Empty) were incubated with 42 heat-inactivated human sera followed by an anti-human-IgG-AlexaFluor488-conjugate: 12 with BC, 11 with TA, 10 with both BC and TA and 9 with non-autoimmune thyroid diseases. The Kolmogorov-Smirnov Test was used to compare the fluorescence intensity obtained with CHO-NIS and CHO-Empty, using sera from six young males as a negative control population. None of the 42 sera were positive for NISAb. NISAb are rare and NIS is unlikely to be a common thyroid/BC shared antigen. We have recently demonstrated TPO expression in BC tissue and are currently investigating TPOAb cross-reactivity with TPO/LPO.

Post-lobectomy Hypothyroidism: Incidence and Risk Factors

Background: Risk factors for developing hypothyroidism after hemithyroidectomy have not been sufficiently studied and the incidence of this complication has probably been underestimated. One factor that has been associated is the autoimmune thyroiditis but hypothyroidism is a normal occurrence in the natural course of this disease and is independent of the surgical approach. Methods: Study cohort of patients subjected to thyroid lobectomy secondary to benign (non autoimmune) thyroid disease with a minimal 4-year postsurgical follow-up. Independent variables studied were age, gender, nutritional status as expressed by body mass index (BMI), and TSH levels, and the dependent variable was development or not of hypothyroidism. Incidence and relative risk for each variable were studied. Results: We included 179 patients, 164 women with a mean age of 41.9 years and 15 men with a mean age of 40.6 years. Pathological substrates were nodular colloid goiter in 115 cases, follicular adenoma in 33 cases, adenomatous colloid goiter in 26 cases, and simple cyst in 5 cases. Sixtyseven (37.4%) patients developed hypothyroidism, 45 (67.2%) of these cases within the first 6 weeks of surgery and 22 (32.8%) cases at 6-month follow-up. No further cases of hypothyroidism were identified after 6 months and up to a mean followup of 4 years. The only risk factor associated was a preoperative BMI over 25. Conclusion: For patients undergoing lobectomy for a benign non-autoimmune thyroid disease and Original Research Article Hurtado-Lopez and Alfaro-Zebadua; BJMMR, 6(2): 158-163, 2015; Article no.BJMMR.2015.192 159 a BMI over 25, there is a 1.8-fold higher risk of developing hypothyroidism. The incidence of hypothyroidism in patients undergoing hemithyroidectomy is 37.4% and occurs in the first 6 months after surgery.