Autoimmune Thyroiditis and Vitamin D.

Hashimoto's thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods.

Hashimoto's Encephalopathy: Case Series and Literature Review.

PURPOSE OF REVIEW: To describe the clinical manifestations of Hashimoto's encephalopathy (HE) and discuss its pathogenesis in light of recent research. RECENT FINDINGS: The pathogenesis of HE is uncertain. Available evidences point towards an autoimmune etiology due to vasculitis or other inflammatory process. Detection of thyroid antibodies - antithyroid peroxidase and anti-thyroglobulin are essential for diagnosis. Autoimmune encephalitis including Anti-IgLON5 disease needs to be excluded in suspected cases with appropriate tests for neuronal surface antibodies. Detection of thyroid autoantibodies is nonspecific, as these can be detected in some normal individuals and in other autoimmune diseases. In recent years, attention has turned to an aggressive form of Hashimoto's thyroiditis accompanied by elevated serum IgG4 levels in younger males with very high levels of thyroid antibodies. The role of the thyroid autoantibodies in the central nervous system (CNS) tissue damage remains unclear and these can act only as markers for diagnosis. Conversely, they have a role to play in determining the thyroid pathology - more glandular fibrosis associated with thyro-peroxidase antibody than with the thyroglobulin antibody. HE is a syndrome characterized by altered mental status, confusion, hallucinations, delusions, and sometimes seizures, in association with high serum anti-thyroid antibody concentration that is usually responsive to glucocorticoid therapy. Diagnosis requires the exclusion of other causes of encephalopathies and encephalitis including autoimmune encephalitis associated with neuronal surface antibodies and paraneoplastic ones. Diagnosis also is dependent on the demonstration of thyroid autoantibodies in serum. Since there is no direct pathophysiologic link between antithyroid antibodies, Hashimoto thyroiditis and the cerebral syndrome, the nomenclature HE could be misleading. The response to steroids led to a renaming of the syndrome to steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), though some cases do not respond to steroids. In recent years, attention has turned to an aggressive form of Hashimoto's thyroiditis accompanied by elevated serum IgG4 levels (IgG4-related disease). This is characterized by a higher incidence in men (5:1) than in women, onset at a younger age, more intense thyroid inflammation and higher antithyroid antibody titters. Such patients have excessive production of IgG4 + plasmacytes, which infiltrate various organs leading to their fibrosis and sclerosis, sometimes resulting in inflammatory tumors. HE is treated with corticosteroids along with treatment of the dysthyroid condition, if any. There are yet no guidelines regarding steroid dose and/or duration.

Autoimmune thyroid status in subclinical thyroid disorders in patients attending a tertiary care center in Nepal: a hospital-based cross-sectional study.

BACKGROUND: Thyroid dysfunction is the leading endocrine disorder worldwide. Iodine deficiency disorders, which were once the major etiology of thyroid dysfunctions, now have been succeeded by autoimmune thyroid diseases with the rise in aberrant salt ionization protocols. This study endeavors to access the level of thyroid autoantibodies viz. anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TGA), and anti-thyroid stimulating hormone receptor (TRAb) in individuals with subnormal thyroid profiles. METHODS: This hospital-based cross-sectional study was conducted at the Department of Clinical Biochemistry, Tribhuvan University for a period of six months. Using non-probability (purposive) sampling method, a total of 60 patients were enrolled with subnormal thyroid profiles to include the population who have not yet started medication. Thyroid hormones (free T3, free T4, TSH) and thyroid antibodies (anti-TPO, TGA, and TRAb) were measured. For non-parametric data, Chi-square test and Kruskal-Wallis test were used. Spearman's correlation was done to determine the association between variables. RESULTS: Out of 60 participants, the majority of the population between 25 and 44 years were diagnosed with thyroid dysfunction with female preponderance. Among all, 40% (n = 24) had subclinical hyperthyroid states while, 60% (n = 36) had subclinical hypothyroid states, and 75% (n = 45) of the total exhibited positive thyroid antibodies. In subclinical hypothyroid patients with TSH above 10 µIU/ml, anti TPO (58.5%) and TGA (66.7%) positivity were highly prevalent. On the other hand, TRAb was exclusively positive in hyperthyroid condition (50% among the group) which is by far the first of its kind reported in Nepal. CONCLUSION: The rise in autoimmune thyroid disease among the Nepalese population infers that addressing iodine deficiency simply through salt iodinization may not be adequate to deal with the rising burden of thyroid disorders, especially in iodine-depleted areas. Also, the increasing prevalence of thyroid autoantibodies positivity in subclinical hypothyroidism in the Nepalese population accounts for the arduous screening and monitoring of autoimmune thyroid disorders in Nepal.

Clinical correlates and thyroid hormones of metabolic syndrome in first-episode and drug-naïve major depressive disorder outpatients with and without hyperglycemia: a comprehensive cross-sectional study.

Hyperglycemia and metabolic syndrome (MetS) are common in patients with major depressive disorder (MDD). This study aimed to explore the prevalence and clinical factors of MetS in first-episode and drug-naïve MDD (FEDND) patients with and without hyperglycemia. A total of 1,718 FEDND patients' symptoms were assessed using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and positive subscale of the Positive and Negative Syndrome Scale (PANSS). Blood glucose levels, metabolic index, and thyroid hormones were measured during fasting. The prevalence of MetS in FEDND patients with hyperglycemia was 35.67 times higher than in FEDND patients without hyperglycemia. FEDND patients with MetS were older, had later age of onset, and were predominantly married than those without MetS (p < 0.05). Among FEDND patients without hyperglycemia, suicide attempts, severe anxiety, HAMD, HAMA, PANSS subscale scores, thyroid stimulating hormone, antithyroglobulin, and total cholesterol levels were all higher in patients with MetS than those without MetS (all p < 0.05). In FEDND patients without hyperglycemia, the combination of age and TgAb distinguished those patients with and without MetS. Our results suggest a high prevalence of MetS in FEDND patients with hyperglycemia. Several clinical variables and thyroid function-related hormones impact MetS in patients with FEDND.

Persistent or Recurrent Disease in Thyroid Cancer Survivors Who Have Elevated Serum Antithyroglobulin Antibodies.

OBJECTIVE: Detection of residual differentiated thyroid cancer is important but difficult. A variety of imaging modalities and biochemical markers has been used with moderately good success. We hypothesized that elevated perioperative serum antithyroglobulin antibody (TgAb) levels would also be a predictive marker for persistent or recurrent thyroid cancer. METHODS: We performed a retrospective analysis of 277 differentiated thyroid cancer survivors divided into 2 groups: (1) those with low or normal serum TgAb (TgAb-) and (2) those with elevated serum TgAb (TgAb+). All patients were seen at one major academic medical center. Patients were followed for a median of 7.54 years. RESULTS: Patients in the TgAb+ group were more likely to have positive lymph nodes at initial surgery, to be assigned to a higher American Joint Committee on Cancer stage, and to have significantly higher incidence of persistent/recurrent disease. The higher incidence of persistent/recurrent cancer was significant under univariable and multivariable (including TgAb status, age, and sex) Cox proportional hazards model analysis. CONCLUSION: We conclude that individuals with elevated serum TgAb at the outset should be followed with a higher index of suspicion for persistent/recurrent thyroid cancer.

Prognostic value of preoperative thyroid autoantibodies for post-thyroidectomy patient pathology: A retrospective cohort study.

OBJECTIVE: The aim of this study was to evaluate the clinical value of preoperative thyroid autoantibodies with reference to the post-thyroidectomy patient pathology. DESIGN: A retrospective cohort study. SETTING: Two tertiary care academic hospitals. MATERIALS AND METHODS: A total of (n = 473) subjects who underwent thyroidectomy from 2009 to 2019 were included. Preoperative serum thyroid autoantibodies (anti-thyroglobulin [anti-Tg] and anti-thyroperoxidase [anti-TPO]) were measured, and the potential predictors of postoperative pathological diagnosis (age, gender, and thyroid autoantibodies) were assessed using multivariable regression models. RESULTS: Patients with positive thyroid autoantibodies were more likely to have malignant disease than benign disease; adjusted odds ratio (AOR) = 1.6 (1.3-2.7, p = 0.002) for anti-Tg, and AOR = 1.6 (1.1-2.5, p = 0.027) for anti-TPO. A subset analysis of the same predictors performed on patients with cancer (malignant vs. microcarcinoma) showed that patients with ages ≥40 were more likely to develop microcarcinoma as opposed to malignant disease; AOR = 1.8 (1.1-3.1, p = 0.03) for anti-TPO, and AOR = 1.7 (1.0-2.9, p = 0.04) for anti-Tg. CONCLUSION: Preoperative thyroid autoantibodies could be used clinically to predict the risk of malignancy in thyroid nodules, thus helping guide treatment decisions in patients with thyroid nodules and speeding up the decision to undergo surgical intervention.

Indication for radioactive iodine in patients with papillary thyroid carcinoma without apparent disease after total thyroidectomy but with elevated antithyroglobulin antibodies.

OBJECTIVE: To evaluate a criterion for the selective indication of radioactive iodine (RAI) based on the short-term behaviour of antithyroglobulin antibodies (TgAb) in patients with papillary thyroid carcinoma (PTC) who have negative thyroglobulin (Tg) and neck ultrasonography (US) without abnormalities after total thyroidectomy but elevated TgAb. DESIGN: This was a prospective study that evaluated 216 patients with low- or intermediate-risk PTC who had nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities but elevated TgAb 3 months after thyroidectomy. RAI was not indicated in patients with negative TgAb or a >50% reduction in TgAb concentrations 6 months after initial assessment followed by a negative test or an additional reduction (also >50%) after 12 months. RESULTS: Only two of the 114 patients who did not receive RAI developed recurrences; another 108 patients met the criterion of an excellent response to therapy in the last assessment and TgAb persisted in four patients but there was an additional reduction in their concentration during follow-up. Among the 102 patients who received RAI, post-therapy whole-body scanning (RxWBS) detected persistent disease in 8 (8%). Two of the 94 patients without persistent disease on RxWBS developed recurrences. In the last assessment, in the absence of additional treatment, 54/92 patients (58.7%) without structural recurrence had negative TgAb. CONCLUSIONS: The indication for RAI can be based on the short-term behaviour of TgAb in patients with PTC and elevated TgAb after thyroidectomy who are not high risk and who do not have apparent disease (nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities).

Association between thyroid autoimmunity and the decline of ovarian reserve in euthyroid women.

RESEARCH QUESTION: Is thyroid autoimmunity (TAI) associated with the decline of ovarian reserve in euthyroid women? DESIGN: Case-control study. Data from 4302 euthyroid women with normal ovarian reserve (NOR) and low ovarian reserve (LOR), including biochemical premature ovarian insufficiency (POI) and overt POI, were retrospectively analysed. The prevalence and effect of TAI on ovarian reserve was evaluated between women with NOR and LOR. Status of ovarian insufficiency and TSH levels was further stratified for analysis. The correlation between anti-thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb) titres and ovarian reserve markers was also determined. RESULTS: The prevalence of positive TAI and TgAb was equally distributed between women with NOR and LOR (P = 0.080, P = 0.172); the prevalence of TPOAb positivity was higher in the LOR group (P = 0.005). After stratifying ovarian reserve and TSH, positive TAI, TPOAb and TGAb were significantly associated with overt POI when TSH was >2.5 µIU/ml (all P < 0.001); no association was observed with biochemical POI or overt POI when TSH was ≤2.5 µIU/ml. No correlation was found between TPOAb, TGAb titres and AMH (P = 0.218, P = 0.368, respectively), and bilateral AFC (P = 0.184, P = 0.315, respectively) in patients with LOR; only TPOAb titre was positively correlated with FSH (P = 0.039). CONCLUSIONS: Among the whole population of euthyroid women, TAI was not associated with low ovarian reserve but was significantly associated with overt POI in women with TSH>2.5 µIU/ml. Further basic studies on underlying mechanisms are needed.

Histology is more ιmportant than persistent anti-Tg antibodies for progression of differentiated thyroid cancer.

CONTEXT: Anti-thyroglobulin antibodies (anti-Tg), present in 20%-25% of differentiated thyroid cancer (DTC) patients, interfere with thyroglobulin measurements posing a challenge in the follow-up. OBJECTIVES: The aim of this study was to identify clinical-histological factors that may affect anti-Tg persistence and disease outcome in DTC with positive anti-Tg. METHODS: We retrospectively studied 234 DTC patients, with positive anti-Tg at diagnosis (females: 82.1%, age at diagnosis: 46.0 ± 14.4 yrs, median follow-up: 5 yrs (1.5-32 yrs). 221/234 (94.4%) received radioiodine (RAI) ablation. Patients were divided into two subgroups: those whose anti-Tg became undetectable (anti-Tg-NEG) and those whose anti-Tg remained positive (anti-Tg-POS) at the end of the follow-up period. RESULTS: Anti-Tg-POS patients (n = 80, 34.2%) compared to anti-Tg-NEG (n = 154, 65.8%) had more frequently lymph node infiltration (36.3% vs 20.1%, P = .01), extrathyroidal extension (ETE, 35.0% vs 22.1%, P = .04), poorly differentiated DTC and increased tumour size (P ≤ .004). They received higher total RAI dose (P < .001). In most cases, additional RAI administration and/or additional surgeries did not lead to anti-Tg elimination. These had more frequently structural disease persistence/progression compared to anti-Tg-NEG (remission: 78.8% vs 95.5%, persistence: 13.8% vs 3.9%, progression: 7.5% vs 0.6%, P < .001). In Kaplan-Meier analysis, the probability of disease progression was higher in anti-Tg-POS. In Cox proportional hazard analysis, the predictors of disease progression were size (P = .002) and ETE (P = .006). CONCLUSIONS: Worse histological features are more frequent in patients with anti-Tg persistence during follow-up. Further additional RAI administration and/or surgeries do not affect anti-Tg elimination in most cases. Anti-Tg persistence correlates with structural persistence although tumour size and extrathyroidal extension are the main predictors of disease progression.

Investigation of thyroid blood tests and thyroid ultrasound findings of patients with rosacea.

We aimed to investigate the relationship between rosacea and thyroid diseases by analyzing thyroid blood tests and ultrasound findings of our patients recently diagnosed with rosacea. This study was designed as a prospective, single-center study. Dermatological examination findings, lesion locations were recorded, and rosacea clinical scores were calculated for all study group patients. The control group consisted of completely healthy women presented to our hospital during the study period for check-up purposes. Serum-free thyroxine, free triiodothyronine, thyroid-stimulating hormone, antithyroglobulin antibody, antithyroid peroxidase antibody levels were measured, and thyroid ultrasound examinations were performed for all study participants. The entire study cohort consisted of 123 patients (63 cases and 60 controls). There was no significant difference between the groups in terms of mean patient age (P < .05). Cheek was the most common lesion location (96.8%). There was no difference between the groups in terms of thyroid-related laboratory parameters. However, anti-TPO levels differed significantly with increasing disease severity (ie, RCSs). There were significant relationships between cheek lesions and fT4 (P = .021), while nose and chin lesions were associated with fT3 (P = .01, P = .001). Thyroid ultrasound findings revealed that rosacea patients tended to have larger thyroid nodules and more heterogeneous thyroid parenchymas than controls. Our findings indicate that thyroid blood tests, including thyroid autoantibodies, should be tested and thyroid ultrasounds should be performed in patients diagnosed with rosacea. However, these findings need to be validated by prospective studies conducted in larger patient series with more extended follow-up periods.

Autoimmune thyroid disease in children with diabetes and adolescents: A single center study from south Punjab.

OBJECTIVE: To evaluate the prevalence of autoimmune thyroid disease in children with diabetes. METHODS: The descriptive cross-sectional study was conducted from January to December 2019 at the Children Hospital and the Institute of Child Health, Multan, Pakistan, and comprised paediatric type 1 diabetes mellitus patients of both genders. Blood samples were obtained for detailed testing of thyroid functions tests. Data was analysed using SPSS 20. RESULTS: Of the 161 paediatric subjects, 83(51.6%) were boys. The overall mean age was 9.7±4.3 years. Thyroid peroxidase antibody was positive in 34(21.1%) patients and thyroglobulin antibody in 27(16.7%). Both antibodies were positive in 17(10.5%) patients. Six (3.7%) patients had evidence of subclinical hypothyroidism, 8(4.9%) had overt hypothyroidism and 1(0.62%) had hyperthyroidism. CONCLUSIONS: The prevalence of autoimmune thyroid disease among children and adolescents with type 1 diabetes mellitus was 21%, with hypothyroidism being more prevalent compared to hyperthyroidism.

Prevalence of Thyroid Autoimmunity in Women with Recurrent Pregnancy Loss.

Background and objectives: Thyroid autoimmunity (TAI) has been associated with a significantly increased risk of miscarriage in women with recurrent pregnancy loss (RPL). The aim of this study was to determine the prevalence of TAI in women with RPL and compare the clinical characteristics of positive and negative TAI women. Materials and Methods: This is a retrospective cross-sectional study; 203 women with RPL were included. Thyroid profile, anti-thyroid peroxidase (TPO-Ab), and anti-thyroglobulin (TG-Ab) antibodies were measured in all participants. Clinical characteristics and causes of RPL were compared between positive and negative TAI. Results: Prevalence of TAI was 14.8%; prevalence of positive TPO-Ab and TG-Ab was 12.3% and 4.9%, respectively. Women with TAI had significantly higher concentrations of thyrotropin (TSH) compared to women without TAI (4.8 ± 3.8 versus 3.1 ± 1.1, p = 0.001). There was no significant difference in age, the number of gestations, miscarriages, state of antiphospholipid antibodies (aPL), or causes of RPL between women that were TAI-positive versus TAI-negative. Prevalence of positive TAI by cause of RPL was: endocrine 7/25 (28%), genetic 1/5 (20%), autoimmune 1/5 (20%), anatomic 8/55 (14.5%), and unexplained cause 13/112 (11.6%). Conclusions: The prevalence of TAI in women with RPL is 14.8%. Women with an endocrine cause have the highest prevalence of TAI.

Excellent diagnostic performance of FNA-Tg in detecting lymph nodes metastases from papillary thyroid cancer.

Background: Thyroglobulin washout of fine needle aspiration (FNA-Tg) has proved to be useful in detecting lymph node metastases from papillary thyroid cancer; however, the influences of thyroid gland, Hashimoto thyroiditis, serum thyroglobulin (Tg) and anti-TG antibody on the diagnostic performance of FNA-Tg are controversial. Patients & methods: We retrospectively collected the FNA-Tg results of 176 preoperative or postoperative patients (356 lymph nodes) who finally were diagnosed with papillary thyroid cancer. The diagnostic abilities of FNA-Tg were evaluated and compared under different circumstances. Results: The diagnostic performance of FNA-Tg was uninfluenced irrespective of the status of thyroid gland or serum anti-TG antibody. However, high serum Tg was positively correlated with FNA-Tg (Exp(B) = 1.57; 95% CI: 1.209-2.309; p = 0.001). Conclusion: FNA-Tg was an excellent diagnostic tool, but it should be interpreted with caution only if serum Tg is higher than 10 ng/ml.

Thyroid disorders in Taiwanese children with Down syndrome: The experience of a single medical center.

BACKGROUND/PURPOSE: Thyroid disorders are common in children with Down syndrome (DS), however, such data have rarely been reported in Taiwanese children. This study presents our experience with the management of these children. METHODS: Between 2006 and 2016, 51 children (31 boys and 20 girls) with DS were enrolled. Thyroid function was evaluated and natural course of thyroid status were analyzed. RESULTS: Of 51 patients with DS, 2 had congenital hypothyroidism due to dyshormonogenesis. Of the remaining 49 patients, 30 (61%) had euthyroidism (EuT), and 19 (39%) had subclinical hypothyroidism (SH). Eighteen (37%) had detectable thyroid antibodies. It occurred at any age and the incidence was not affected by sex. The mean follow-up duration for 39 DS children was 3.8 ± 2.4 years. Of the 26 children who had EuT at enrollment and were followed up, 22 remained EuT, 2 developed SH, 1 developed overt hypothyroidism, and 1 developed overt hyperthyroidism. Of the 13 patients with SH who were followed up, 1 was treated for high thyroid-stimulating hormone levels, 8 became EuT, and 4 maintained SH status. Children with DS and persistent SH had significantly higher maximum thyroid-stimulating hormone levels during follow-up than did those with transient SH. Fluctuation in thyroid status during follow-up was not uncommon in children with DS. CONCLUSION: The prevalence of thyroid disorders is higher in Taiwanese children with DS than in the general population. Because symptoms of hypothyroidism overlap those inherent to DS, regular follow-up of thyroid function in children with DS is indicated.

Implication of VDR Rs7975232 and FCGR2A Rs1801274 Gene Polymorphisms in the Risk and the Prognosis of autoimmune Thyroid Diseases in the Tunisian Population.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) that cause hypothyroidism and hyperthyroidism, respectively. The vitamin D receptor (VDR) and the Fey receptor IIA (FcγRIIA), are implicated in the etiology of AITD. This study was conducted to examine the implication of VDR rs7975232 and FCGR2A rs 1801274 variations in the susceptibility and the prognosis of AITD in the Tunisian population. The rs7975232 and rs1801274 (R131H) polymorphisms were analyzed in 162 controls and 162 AITD patients (106 HT and 56 GD) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification of refractory mutation system-PCR (ARMS-PCR), respectively. No significant difference was demonstrated for the rs7975232 between patients and controls. However, a significant association was shown between the rs1801274 polymorphism and AITD or HT in the dominant (p = 0.03 or p = 0.01), codominant (p = 0.019 or p = 0.026) and allelic (p = 0.011 or p = 0.012) models. The rs7975232 was associated with the absence or the presence of anti-thyroglobulin antibody, with the age of AITD and GD patients during the first diagnosis (p = 0.01 and p = 0.009, respectively) and with a high T4 level at the beginning of HT disease. However, the FCGR2A gene polymorphism was associated with a low T4 level at the beginning of GD disease. In conclusion, this study indicates that only the FCGR2A variation could be related to AITD and HT susceptibility and that VDR and FCGR2A gene variations constitute factors to prognosticate the severity of AITD, HT and GD.

Polymorphisms in TSHR gene and the risk and prognosis of autoimmune thyroid disease in Tunisian population.

BACKGROUND: Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. TSHR is considered as candidate gene in GD. This finding prompted us to investigate the association of TSHR gene polymorphism with the risk and the prognosis of AITD in Tunisia. METHODS: A total of 84 healthy controls and 91 patients with AITD (69HT and 22 GD) were genotyped for TSHR rs74067403A>G polymorphism and 134 healthy controls and 149 patients with AITD (98 HT and 51 GD) were genotyped for TSHR rs1054708 T>C polymorphism. RESULTS: For rs1054708, we found an association between HT, AITD and the heterozygous genotype TC, the mutated genotype CC and the genotypes presented the mutated allele C (TC+CC) and with mutated allele C. The heterozygous genotype TC and the genotypes that presented the mutated allele C of rs1054708 are associated with male patients with AITD evenly the heterozygous genotype TC is associated with age of onset of disease. CONCLUSIONS: These preliminary results suggest that TSHR rs1054708 polymorphism may be a protective factor against HT and AITD. This polymorphism can affect the etiology of AITD between men and women and also by age.

The value of preoperative antithyroidperoxidase antibody as a novel predictor of recurrence in papillary thyroid carcinoma.

The link between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is widely recognized. Considering the strong association between raised antithyroidperoxidase antibody (TPOAb) and CLT, we postulated that the preoperative TPOAb can predict the prognosis of PTC, particularly for recurrence. A total of 2,070 patients who underwent total thyroidectomy for classical type PTC with tumor size ≥1 cm and with available data on preoperative TPOAb and TgAb were enrolled to compare disease-free survival (DFS) according to the presence of preoperative TPOAb, TgAb, and coexistent CLT. Patients with positive preoperative TPOAb had a significantly better DFS compared to patients without positive preoperative TPOAb (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.30-0.94, p = 0.028) while no difference in DFS was found according to preoperative TgAb status. Positive preoperative TPOAb was an independent prognostic factor for structural persistent/recurrent disease after adjustment for major preoperative risk factors such as age, sex, and tumor size (HR 0.52, 95% CI 0.28-0.99, p = 0.048). Although the coexistence of CLT lowered the risk for structural persistence/recurrence in univariate analysis (HR 0.52, 95% CI 0.31-0.86, p = 0.012), it was not an independent favorable prognostic factor by multivariate analysis (HR 0.65, 95% CI 0.38-1.10, p = 0.106). However, when coexistent CLT was combined with positive preoperative TPOAb, it indicated an independent protective role in structural persistent/recurrent disease (HR 0.39, 95% CI 0.16-0.98, p = 0.045). Our study clearly showed that presence of preoperative TPOAb can be a novel prognostic factor in predicting structural persistence/recurrence of PTC.

Role of antithyroid autoimmunity as a predictive biomarker of chronic immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia. Pediatric ITP patients are prone to develop autoantibodies such as antithyroglobulin (TG) and antithyroperoxidase (TPO), even in the absence of clinical signs of autoimmune disease. The aim of this multicenter retrospective study was to evaluate (1) the prevalence of positivity of antithyroid antibodies (TPO and TG) in a large cohort of pediatric patients with chronic ITP; (2) the role of autoimmune thyroiditis as a prognostic factor for chronicity of ITP. PROCEDURE: For this retrospective study, we collected data from patients diagnosed as affected by chronic ITP between 2011 and 2014 in six centers belonging to the Italian Association of Pediatric Haematology and Oncology (AIEOP). RESULTS: From the analysis of data, we found a significantly higher prevalence of antithyroid antibodies in children with chronic ITP (11.6%) than in the pediatric population (1.2%-1.3%). No correlation has been found between the platelet count and the prevalence of positive antithyroid antibodies at any detection time of the study. CONCLUSIONS: The results of our study demonstrated that (1) the prevalence of positivity for antithyroid antibodies (anti-TPO and anti-TG) in pediatric patients with chronic ITP results is significantly higher than in the pediatric population; (2) autoimmune thyroiditis does not seem to play a role as a prognostic factor for chronicity of ITP in pediatric patients.

Thyroglobulin measurement in the management of patients with differentiated thyroid cancer.

The post-operative management of patients with differentiated thyroid carcinoma (DTC) relies on serial measurements of serum thyroglobulin. Current methodologies for thyroglobulin quantitation vary in their analytical and clinical performance. For years, thyroglobulin radioimmunoassays (RIA) and immunometric assays (IMA) have been used despite analytical interferences from anti-thyroglobulin autoantibodies (TgAb) as well as heterophile antibodies (HAb). TgAb interference limits Tg utility as a tumor marker in ∼30% of TgAb-positive patients. Consequently, additional studies are necessary to rule out persistent or recurrent disease in these patients. Recently, thyroglobulin mass spectrometry assays have been introduced as a solution to the interference problems observed in immunoassays. However, their analytical sensitivity is inferior to the high sensitivity immunoassays. The aims of this review are to: (i) review current thyroglobulin assays; (ii) discuss technical limitations of each assay; and (iii) discuss the clinical uses of thyroglobulin in serum and fine-needle aspirate biopsy washouts for the management of DTC patients. An understanding of the technical advantages and disadvantages of Tg assays is critical for clinicians and laboratorians to effectively use and interpret this test in the management of DTC patients.

Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab.

Thyroid dysfunction (TD) induced by immune checkpoint inhibitors is not sufficiently understood. The purpose of this retrospective observational study was to identify risk factors and the clinical course of TD induced by nivolumab. Patients with advanced solid tumors who were treated with nivolumab from March 2009 through to March 2016 at the National Cancer Center Hospital (Tokyo, Japan) were included. Thyroid function and antithyroid Abs from serum samples among all patients were evaluated at baseline and during nivolumab treatment. Overt hypothyroidism was defined as low serum-free T4 together with elevated thyroid-stimulating hormone (TSH) >10 µIU/mL. Thyrotoxicosis was defined as low TSH with elevated free T4 and/or free T3. We defined thyroid autoimmunity as the presence of antithyroid Abs at baseline, including antithyroid peroxidase Abs and antithyroglobulin Abs (TgAb). Twenty-three (14%) of a total of 168 patients developed TD, including 17 cases of hypothyroidism and 20 of thyrotoxicosis. Thyrotoxicosis followed by hypothyroidism occurred in 14 cases. Fourteen of 35 patients (40%) with thyroid autoimmunity developed TD vs 9 of 133 (7%) without (odds ratio 9.19; 95% confidence interval [CI], 3.53-23.9). In multivariate analysis, elevated TSH and TgAb at baseline were significantly associated with the development of TD, with odds ratio of 7.36 (95% CI, 1.66-32.7) and 26.5 (95% CI, 8.18-85.8), respectively. Association between TD and elevated antithyroid peroxidase Abs at baseline was not significant. These results suggest that patients with pre-existing TgAb and elevated TSH at baseline are at high risk of TD.