Positive Anti-thyroid Peroxidase Research Articles

TH1.10 Antithyroid peroxidase antibodies and histopathological outcomes in Egyptian patients subjected to total thyroidectomy for nonmalignant nodular goiter. Retrospective study

Abstract Introduction Thyroid is an endocrine gland. It produce T3 and T4 hormones through a series of enzymatic actions. These hormones regulate body metabolism and physiology. Immune disorders in this gland can cause hypo/hyperthyroidism. Objective The study aimed to assess antithyroid antibodies in patients with benign thyroid masses and the effect of total thyroidectomy on the antibodies titres. Patients and Methods This is a retrospective work of 112 cases managed with total thyroidectomy who have positive antithyroid peroxidase antibodies (TPO-Ab), antithyroglobulin antibodies (Tg-Ab), or both. All patients were euthyroid before surgery. Thyroid function tests and thyroid antibodies levels were measured before and 6 and 12 months after surgery. Results Histopathological evaluation revealed Hashimoto thyroiditis (47.3%), colloid nodules (22.3%), and lymphocytic thyroiditis (30.4%). All patients were TPO-Ab positive, while 96 patients (85.7%) were Tg-Ab positive before surgery. There was no considerable change in TPO-Ab and Tg-Ab after surgery (p = 0.817, and p=0.560, respectively). Also, there was no significant difference between the three histopathological diagnoses in the levels of TPO-Ab (p = 0.086) or Tg-Ab (p = 0.673). Conclusions Antithyroid antibodies are not valuable markers for diagnosis or prognosis of benign thyroid diseases subjected to total thyroidectomy. We do not recommend their use beyond being a supportive evidence of the possibility of autoimmune nature of the disease if other criteria are confirmed.

GWAS of Chronic Spontaneous Urticaria Reveals Genetic Overlap with Autoimmune Diseases, Not Atopic Diseases

Although chronic spontaneous urticaria (CSU) is a common disease, GWASs of CSU are lacking. We aimed to identify susceptibility SNPs by performing a GWAS in Chinese Han adults with CSU. The discovery cohort included 430 CSU cases and 482 healthy controls. The GWAS findings were validated in 800 CSU cases and 900 healthy controls. Genetic, functional enrichment, and bioinformatic analyses of genome-wide significant SNPs were performed to assess the association between CSU and autoimmunity or atopy. Five genome-wide significant SNPs were identified: rs434124/LILRA3, rs61986182/IGHG1/2, rs73075571/TDGF1, rs9378141/HLA-G, and rs3789612/PTPN22. The first four SNPs were in linkage disequilibrium with autoimmune-related diseases‒associated SNPs and were cis-expression quantitative trait loci in immune cells. The five SNPs-annotated genes were significantly enriched in immune processes. Higher polygenic risk scores and allele frequencies of rs3789612∗T, rs9378141∗C, and rs73075571∗G were significantly associated with autoimmune-related CSU phenotypes, including positive antithyroglobulin IgG, positive anti-FcεRIα IgG, total IgE <40 IU/ml, and positive antithyroid peroxidase IgG but not with atopic or allergic sensitized CSU phenotypes. This GWAS of CSU identifies five risk loci and reveals that CSU shares genetic overlap with autoimmune diseases and that genetic factors predisposing to CSU mainly manifest through associations with autoimmune traits.

The prevalence of thyroid dysfunction and thyroid autoantibodies among patients with rheumatoid arthritis

Background and objective: Rheumatoid arthritis is a chronic and inflammatory autoimmune systemic disease of unknown cause that may affect many tissues and organs. Rheumatoid arthritis and thyroid disorders may occur in the patient simultaneously. The main antigens that give rise to thyroid antibodies are thyroglobulin, thyroid peroxidase, anti-cyclic citrullinated protein, and thyroid hormone receptor. This study aimed to determine the frequency of thyroid dysfunction and seroprevalence of anti-thyroid antibody in patients with rheumatoid arthritis and its association with inflammatory marker C-reactive protein. Methods: A cross-sectional study was performed at Rizgari Teaching Hospital and CMC private hospital, Erbil, Iraq. From 15 January to15 October 2020. A hundred patients with rheumatoid arthritis were included in the study, in addition to 70 controls. The serum levels of biomarkers were determined by the chemiluminescent immunoassay method. Results: Patients with rheumatoid arthritis had 6% of thyroid dysfunctions. Regarding the prevalence of thyroid autoantibodies in patients with rheumatoid arthritis, 9% had positive anti-thyroid peroxidase, 13% had positive anti-thyroglobulin, and 6% were positive for a combination of both. There was a statistically significant (P &lt;0.001) high level of serum anti-cyclic citrullinated protein and C-reactive protein in rheumatoid arthritis than in control. Euthyroid profiles were 73% inrheumatoid arthritis patients and 82.9% in control. Conclusion: The study delineated the co-existence of thyroid disorder in rheumatoid arthritis patients with or without autoimmune origin, besides the increased prevalence of auto-thyroid antibody among rheumatoid arthritis with thyroid dysfunction.

Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria.

BackgroundChronic spontaneous urticaria (CSU) is a common autoimmune skin disease. Little is known about the role of epigenetics in the pathogenesis of CSU. This study aimed to investigate genome-wide DNA methylation profile in whole blood of patients with CSU.Patients and MethodsGenome-wide DNA methylation levels in whole blood samples of 95 Chinese Han ethnicity adult CSU patients and 95 ethnicity-, age- and sex-matched healthy controls were analyzed using Illumina 850K methylation chip. The differentially methylated genes (DMGs) were screened out and then functionally annotated by the gene ontology and the Kyoto encyclopedia of genes and genomes databases.ResultsA total of 439 differentially methylated positions (DMPs) (p < 0.01 and |Δβ| ≥ 0.06) were identified with 380 hypomethylated and 59 hypermethylated. The average global DNA methylation levels of the 439 DMPs in the CSU patients were significantly lower than those in the healthy controls (p < 0.001). The distribution of the 439 DMPs was wide on chromosome 1 to 22 and chromosome X. Chromosome 6 embodied the largest number of DMPs (n = 51) and their annotated genes were predominantly related to autoimmunity. The 304 annotated DMGs were mainly enriched in autoimmune disease- and immune-related pathways. A total of 41 DMPs annotated to 28 DMGs were identified when p < 0.01 and |Δβ| ≥ 0.1. Of the 28 DMGs, HLA-DPB2, HLA-DRB1, PPP2R5C, and LTF were associated with autoimmunity. CSU cases with elevated total IgE, positive anti-thyroid peroxidase IgG autoantibodies, positive anti-thyroglobulin IgG autoantibodies, angioedema, UASday > 4, or recurrent CSU showed phenotype-specific DMPs as compared with cases with normal total IgE, negative anti-thyroid peroxidase IgG autoantibodies, negative anti-thyroglobulin IgG autoantibodies, no angioedema, UASday ≤ 4, or non-recurrent CSU respectively.ConclusionThis study shows a distinct genome-wide DNA methylation profile in Chinese Han ethnicity adult CSU patients and indicates a role of epigenetics in the pathogenesis of CSU. The predominant enrichment of the CSU-associated DMGs in immunological pathways provides supportive evidence for the immunopathogenesis of CSU. Future research on the CSU-associated DMPs and DMGs will help discover potential therapeutic targets for CSU.

Hearing Impairment and Audiological Alterations in Euthyroid Hashimoto’s Thyroiditis

Introduction: Hearing loss may be associated with autoimmune diseases, but it was less studied in Hashimoto’s thyroiditis (HT). We aimed to evaluate hearing impairment and audiological alterations in adults with euthyroid HT. Methods: Adult patients with euthyroid HT (normal thyroid functions, positive antithyroid peroxidase (anti-TPO)/anti-thyroglobulin, and sonographic findings) were compared with controls. We excluded pregnant or older patients (>40 years), those with a history of otological/audiological disease or surgery, otitis media, acoustic trauma, chronic illnesses, use of alcohol, cigarette, medications, rheumatoid factor, antinuclear, antimitochondrial, antiparietal, antineutrophil cytoplasmic, anti-smooth muscle, or antigliadin antibodies, abnormal biochemical or otological findings. Tympanometry which indicates tympanic peak pressure (TPP, daPa), acoustic reflex testing (ART), pure-tone average (PTA), and transient evoked otoacoustic emission (TEOAE) were performed. We grouped the participants according to ART (positive/negative), TEOAE (normal/undetected), and PTA (≤20/>20 decibel). Results: Air conduction thresholds on the right ear at 500, 4,000, 6,000, and 8,000 Hz, PTA, and the left ear at 250, 4,000, 6,000, and 8,000 Hz were higher in euthyroid HT (n = 36) than in controls (n = 40) (p < 0.05). We found less negative TPP and a higher ratio of negative ART in euthyroid HT (p < 0.05). Euthyroid HT predicted undetected TEOAE and increased hearing threshold on the right ear at 500 and 8,000 Hz (p < 0.001). TEOAE detected audiological abnormality at a higher rate. Anti-TPO was positively correlated with TPP and air conduction thresholds, except the right ear at 8,000 Hz. Discussion/Conclusion: Hearing and audiological tests may be impaired in euthyroid HT. We recommend close monitoring of audiological functions in these patients. TE­OAE more specifically indicates audiological abnormality.

Rare Association of Adult Onset Still’s Disease with Autoimmune Thyroid Disease: A Case Report

Adult-onset Still’s disease (AOSD) is an uncommon inflammatory condition presenting with high grade fever, arthralgia, skin rash, and leukocytosis. Autoimmune thyroid disease (AITD) is commonly seen in females in their third to fifth decade and usually missed to screen in other autoimmune diseases. In this study, the case of a 17-year-old female patient from Pune is reported who presented to Bharati hospital in November 2020, with a six-month history of high-grade fever, arthritis, and elevated acute phase reactants along with hypothyroidism. She was diagnosed with AOSD (based on Yamaguchi criteria) and AITD with positive anti-thyroid peroxidase (anti-TPO) antibodies. She responded well to oral steroids and thyroid supplements. This case draws attention to the rare association between AOSD and AITD.

Outcomes of Pregnancy in Euthyroid Women with Positive Thyroid Peroxidase Antibodies

Thyroid disorders are among the most common endocrine disorders affecting pregnant women .Thyroid autoimmunity has been associated with poor pregnancy outcomes. Thyroid Peroxidase antibodies being the most common of thyroid antibodies and it can be considered as a surrogate marker for thyroid related adverse pregnancy outcomes. The present study was conducted to further elucidate the association between these antibodies and adverse pregnancy outcomes. A case control study including 150 randomly selected participant was carried out at AL-Khansaa Teaching Hospital in Mosul, Iraq. over the period of three months. All participants enrolled in the study were screened for Thyroid Function Tests TFTs including Thyroid Stimulating Hormone, Free thyroid hormones (Ft3 and Ft4) as well as Anti-Thyroid Peroxidase antibodies. Pregnant women were then classified depending on their Anti-Thyroid Peroxidase antibodies test results into two groups (positive and negative) groups. All women were followed till delivery to record their pregnancy outcomes. Our results showed that 10% of the screened pregnant women showed positive anti-Thyroid peroxidase antibodies. These women reported a higher incidence of cesarean section and preterm deliveries when compared to negative anti-Thyroid peroxidase antibodies control group. So a conclusion was drawn to recommend anti-Thyroid peroxidase antibodies as screening test during pregnancy especially those with bad obstetric history or history of thyroid disorders.

Antithyroid Peroxidase Antibodies and Histopathological Outcomes in Egyptian Patients Subjected to Total Thyroidectomy for Non-Malignant Nodular Goiter.

ObjectiveThe study aimed to assess antithyroid antibodies in patients with benign thyroid masses and the effect of total thyroidectomy on the antibodies titers.Patients and MethodsThis is a retrospective work of 112 cases managed with total thyroidectomy with positive antithyroid peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (Tg-Ab), or both. All patients were euthyroid before surgery. Thyroid function tests and thyroid antibodies levels were measured before and 6 and 12 months after surgery.ResultsHistopathological evaluation revealed Hashimoto thyroiditis (47.3%), colloid nodules (22.3%), and lymphocytic thyroiditis (30.4%). All patients were TPO-Ab positive, while 96 patients (85.7%) were Tg-Ab positive before surgery. There was no considerable change in TPO-Ab and Tg-Ab after surgery (p = 0.817, and p=0.560, respectively). Also, there was no significant difference between the three histopathological diagnoses in the levels of TPO-Ab (p = 0.086) or Tg-Ab (p = 0.673).ConclusionAntithyroid antibodies are not valuable markers for diagnosis or prognosis of benign thyroid diseases subjected to total thyroidectomy. We do not recommend their use beyond supporting evidence of the possibility of the autoimmune nature of the illness if other criteria are confirmed.

Insights From Prospective Follow-up of Thyroid Function and Autoimmunity Among Covid-19 Survivors

Objective: Occurrence of Graves’ disease and Hashimoto’s thyroiditis after coronavirus disease 2019 (COVID-19) raised the concern about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggering thyroid autoimmunity. Uncertainties remain regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. We carried out a prospective study to characterize the evolution of thyroid function and autoimmunity among COVID-19 survivors. Method: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for confirmed COVID-19 from 21 July to 21 September 2020 were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and anti-thyroid antibodies were measured on admission and at 3 months. Positive anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) was defined by >100 units. Results: Among 200 COVID-19 survivors, 122 had reassessment thyroid function tests (TFTs) (median age: 57.5 years; 49.2% men). Baseline characteristics of patients who did and did not have reassessment were comparable. Among the 20 patients with baseline abnormal TFTs on admission, mostly low fT3, 15 recovered. Of the 102 patients with normal TFTs on admission, two (2.0%) had new onset abnormal TFTs, which may represent TFTs in different phases of thyroiditis (one had mildly elevated TSH 5.8 mIU/L, with normal fT4 [16 pmol/L] and fT3 [4.3 pmol/L], the other had mildly raised fT4 25 pmol/L with normal TSH [1.1 mIU/L] and fT3 [4.7 pmol/L]). Among 104 patients with anti-thyroid antibody titers reassessed, we observed increases in anti-TPO (baseline: 28.3 units [IQR 14.0-67.4] vs reassessment: 35.0 units [IQR: 18.8-99.0]; p<0.001) and anti-Tg titers (baseline: 6.6 units [IQR 4.9-15.6] vs reassessment: 8.7 units [IQR: 6.6-15.4]; p<0.001), but no change in anti-TSHR titer (baseline: 1.0 IU/L [IQR: 0.8-1.2] vs reassessment: 1.0 IU/L [IQR: 0.8-1.3]; p=0.486). Of the 82 patients with negative anti-TPO at baseline, 16 had significant interval increase in anti-TPO titer by >12 units (2×6 [precision of the anti-TPO assay in normal range being 6 units per SD]), of these, four became anti-TPO positive. Factors associated a significant increase in anti-TPO titer included worse baseline clinical severity (p=0.018), elevated C-reactive protein during hospitalization (p=0.033), and higher baseline anti-TPO titer (p=0.005). Conclusion: Majority of thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis could occur during convalescence, though uncommon. Importantly, we provided the novel observation of an increase in anti-thyroid antibody titers post-COVID-19, suggesting the potential of SARS-CoV-2 in triggering thyroid autoimmunity, which warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

What Are the Common Characteristics of Pediatric Patients With Antibody Negative Primary Hypothyroidism?

Background: The most common cause of acquired primary hypothyroidism is autoimmune thyroiditis which is typically associated with positive anti-thyroid peroxidase and/or anti-thyroglobulin antibodies. However, some children present with primary hypothyroidism and negative antibodies. Whether there are differences between patients with acquired primary hypothyroidism who have positive vs negative anti-thyroid antibodies has not been systematically examined. Aim:To define the characteristics of patients with primary hypothyroidism and negative antibodies. Methods: A retrospective chart review of patients with hypothyroidism seen in the pediatric endocrine clinic at Riley Hospital for Children in Indianapolis, Indiana from August 2016 until December 2019 was performed. Variables examined included age at diagnosis, signs and symptoms at presentation, height, weight, BMI, TSH, FT4, T4, thyroid peroxidase and anti-thyroglobulin antibodies, family history of thyroid disease, physical exam at diagnosis, and associated diseases. Results: Of 173 patients aged 10.6 ± 3.9 years, 128 (74%) had positive antibodies and 44 (26%) had negative antibodies. Of those with positive antibodies, 80 % were female and 20% were male. Of those with negative antibodies, 53% were female and 47% were male. No differences were seen in the incidence of obesity or Down syndrome in patients with positive antibodies compared with those who had negative antibodies. A positive family history of thyroid disease was present in 45% of those with positive antibodies and in 22% of those with negative antibodies, P=0.006 Fifty-eight patients (45%) with positive antibodies reported excessive fatigue and 40 (31%) had a goiter. In contrast, 10 (22.7%) who had negative antibodies reported mild intermittent fatigue, P=0.006 and 7 (15.9 %) had a goiter, P=0.04 The average TSH in the antibody positive group was 129± 230 mcu/ml compared with 48 ± 131 mcu/ml in those with negative antibodies, p=0.04. A trend was also noted for a lower FT4 in those with positive antibodies (0.68±0.37 vs 0.85±0.27, p=0.050) No other differences in baseline characteristics were seen between patients with negative vs positive antibodies. Conclusion: Patients with positive anti-thyroid antibodies had more severe hypothyroidism and were more likely to report extreme fatigue than those with negative antibodies. It is unknown why some children with acquired primary hypothyroidism presumed due to autoimmune thyroid disease have negative antibodies. Long-term follow-up will be needed to determine whether the natural history of thyroid disease in children with primary hypothyroidism is associated with antibody status.

Inadvertent Excessive Soy Intake as Part of a Weight Loss Program Leading to Rapid Growth of Multinodular Goiter

Background: Over the past few decades consumption of soy products has gained popularity in the U.S. in part due to reports of potential health and weight loss benefits. However, concerns have emerged regarding soy as a potential endocrine-disrupting chemical (EDC) leading to thyroid dysfunction amongst other health issues. Studies have shown a potential association of high soy intake with risk of hypothyroidism and simple goiter (1), but less is known regarding its impact on multinodular goiter. Clinical Case: A 33-year-old female originally from Bolivia without significant medical history presented to our endocrine clinic with complaints of right-sided neck swelling. The swelling was insidious in onset, had gradually increased in size over the past 3-4 months, and become uncomfortable. She denied dysphagia, cough, or shortness of breath. Prior to the onset of symptoms, she had enrolled in a commercial weight loss program. The diet program consisted of limiting caloric intake to multiple meal replacement bars during the day followed by a light dinner of fish and non-starchy vegetables. Examination revealed a palpable right-sided thyroid mass and enlarged thyroid gland. Lab work showed normal TSH, fT4, and T3 levels, positive anti-thyroid peroxidase antibody (anti-TPO Ab) 588 (<=35.0 IU/ml), and negative thyroid-stimulating immunoglobulins (TSI). Ultrasound of the thyroid confirmed the presence of a 4 cm dominant right thyroid nodule and multinodular goiter. Subsequent fine-needle aspiration of thyroid nodule was consistent with benign nodular goiter. Upon further investigation, it was discovered that the meal replacement bars contained a significant amount of soy protein resulting in an excessive intake of 20-40 grams of soy protein daily. We discussed treatment options, and the patient declined thyroid surgery in favor of surveillance following discontinuation of the weight loss products. The patient was advised to consume a varied diet and given follow-up appointments for monitoring. Conclusion: Inadvertent excessive soy intake via meal replacement bars may have triggered the rapid growth of a multinodular goiter in our patient despite reported adequate dietary iodine intake. Soy products often contain isoflavones that may exert an adverse effect on the thyroid by inhibition of TPO, disruption of iodine metabolism, and/or estrogenic activity. We advise that caution be exercised with high soy protein consumption especially in patients with underlying risk factors for multinodular goiter.

Characteristics of Immune-Related Thyroid Adverse Events in Patients Treated with PD-1/PD-L1 Inhibitors.

BackgroundThyroid immune-related adverse events (IRAEs) have been reported in patients treated with programmed cell death protein-1 (PD-1) and programmed cell death protein-ligand 1 (PD-L1) inhibitors. We investigated the incidence and clinical course of PD-1/PD-L1 inhibitor-induced thyroid IRAEs, and identified predictable clinical risk factors of thyroid IRAEs, in particular, overt hypothyroidism (OH).MethodsWe retrospectively reviewed the medical records of 325 cancer patients receiving PD-1/PD-L1 inhibitor in a tertiary referral center.ResultsA total of 50.5% (164/325) of patients experienced at least one abnormal thyroid function following PD-1/PD-L1 inhibitor. Eighty-four patients (51.2%) of them recovered to normal thyroid function during follow-up. In overall population, 25 patients (7.7%) required thyroid hormone replacement therapy due to PD-1/PD-L1 inhibitor-induced OH. Patients who progressed to OH showed significantly higher baseline thyroid stimulating hormone level and longer duration of PD-1/PD-L1 inhibitor therapy than those without thyroid dysfunction or OH (both P<0.001). Median time interval to the development of OH was 3 months after the therapy. OH was significantly associated with positive anti-thyroid peroxidase antibody at baseline and anti-thyroglobulin antibody during the therapy than those without thyroid dysfunction or OH (P=0.015 and P=0.005, respectively). We observed no patients with OH who were able to stop levothyroxine replacement after the cessation of PD-1/PD-L1 inhibitor therapy.ConclusionPD-1/PD-L1 inhibitor-induced thyroid dysfunctions are considerably reversible; however, OH is irreversible requiring levothyroxine replacement even after stopping the therapy. Positive thyroid autoantibodies may predict the progression to OH.

Predicting positive anti-thyroid peroxidase antibody chance in vitamin D deficient patients

Introduction: The relationship between vitamin D deficiency and thyroid gland disorders is controversial. Objectives: Given the prevalence of vitamin D deficiency and the significance of thyroid disorders, the purpose of the study was to examine the relationship between anti-thyroid peroxidase (anti-TPO) antibody and vitamin D deficiency. Patients and Methods: This cross-sectional study was conducted on 35 patients with vitamin D deficiency and 35 people as a control group with normal vitamin D considered more than 20 ng/mL. Serum TSH and anti-TPO antibody tests were assessed for all subjects in both groups. The level of 25 [OH] D3 less than 20 ng/mL was considered as the deficiency of vitamin D and the serum level of anti-TPO antibody more than 40 IU/mL as positive level. Results: Mean age of patients with vitamin D deficiency was 37.00 ± 13.8 years and 46.3 ± 15.9 years in the control group. Mean age in the two groups was different (P=0.010). Around 51.4% of patients had vitamin D deficiency. There were no significant differences in TSH level among the groups (P=0.436). Anti-TPO antibody (anti-TPO Ab) level in 31.4% of the patients with vitamin D deficiency and in 11.4% of patients in the control group was positive with a significant difference (P=0.041). Logistic regression analysis showed the chance of positive anti-TPO Ab in people with vitamin D deficiency was 3.55% of the subjects without vitamin D deficiency (OR = 3.55, 95%, CI: 1.01-12.55, P=0.049). Conclusion: Considering the greater chance (three-fold) of positive anti-TPO Ab titers in patients with vitamin D deficiency in this study, more interventional studies are suggested concerning the effect of vitamin D deficiency on anti-TPO Ab.

Atypical case of VV1 Creutzfeldt‐Jakob disease subtype

AbstractBackgroundCreutzfeldt‐Jakob disease (CJD) is rare form of rapidly progressive dementia due to the presence of abhorrent prion protein and affects 1‐1.5 cases per million per year.1 An estimated 85% of these cases are sporadic, and the remaining 5‐15% develop CJD from inherited mutations of the prion gene.2 Sporadic CJD (sCJD) is further subdivided into six subtypes based on genetic polymorphisms, with the VV1 subtype occurring at a rate of 1 case per one‐hundredth million population per year. 3 These subtypes have been shown to correlate with age of onset, clinical course, disease features and duration4,5. Clinical characteristics of the VV1 subtype has been reported to show, early age of onset (39 years), disease duration of 15 months, elevated 14‐3‐3 and total tau in the CSF, absent PSWCs on electroencephalography (EEG), and magnetic resonance imaging (MRI) hyperintensities in the cerebral cortex with usual negative signal in the basal ganglia or thalamus.6,7, MethodWe present an atypical case of the rarest VV1 sCJD subtype. Contrary to current data on VV1, our patient presented with an unusual age at onset (63 years), longer disease duration (20 months), and positive signal in the basal ganglia on MRI. The real‐time quaking‐induced conversion (RT‐QuIC) was negative.ResultPresenting clinical symptoms included paranoid thoughts and agitation, progressing with rapid memory decline, prosopagnosia, and later development of myoclonus and mutism. Other findings showed positive antithyroid peroxidase antibodies (anti‐TPO), absent PSWCs on EEG, positive 14‐3‐3 and elevated tau on CSF. High dose steroid therapy treatment was administered based on positive anti‐TPO findings, which failed to illicit any improvement and the patient continued to decline.ConclusionTo our knowledge, only two confirmed cases with the VV1 subtype, including our patient, have been reported to have a negative result on RT‐QuIC.8 This may indicate a unique characteristic to VV1 and aid in the diagnostic work up in suspected sCJD cases with this finding. However, given the rarity of our patient’s subtype, and the relatively novel RT‐QuIC, current data is based on a small number of cases and larger cohorts of confirmed VV1 cases with RT‐QuIC testing need to be reported.

Refractory chronic urticaria in adults: clinical characterization and predictors of severity

BackgroundChronic urticaria (CU) is defined as recurrent urticaria lasting for more than 6 weeks.ObjectivesWe aimed to characterize the phenotypes of patients with CU refractory to standard dose anti-H1 antihistamine treatment and search for clinical predictors of poor disease control.MethodsRetrospective collection of data regarding clinical characteristics, comorbidities, treatment, and disease control of all adult refractory CU patients presenting to the Allergy and Immunology Department during 1 year.ResultsSixty-one adult patients were included, 74% females, average age 44.5 years (18 to 84 years old). Most patients (78.7%) had initiated CU less than 1 year before enrolment. Chronic spontaneous urticaria (CSU) accounted for 55.7% of the patients, CSU associated with chronic inducible urticaria (CIndU) as a comorbidity for 44.3%, and angioedema was present in 55.7%. Medically-confirmed psychiatric disorders were present in 78.7%. Complementary diagnostic tests were performed in cases with more severe presentation (UAS7 ≥ 28 and/or UCT < 12) or with longer evolution (> 1 year), corresponding to 42 tested patient. Evidence for autoimmunity (positive anti-thyroid peroxidase antibodies, anti-nuclear antibodies or autologous serum test) was found in 45.2% (n = 19/42), and high C-reactive protein was present in 14.3% (n = 6/42), half of these also had positive antinuclear antibodies. Forty-six patients (75.4%) had at least one significant exacerbation, requiring medical appointment, emergency room, hospitalization or job absenteeism. The number of exacerbations correlated with the presence of angioedema (p = 0.022), with a recent diagnosis (< 1 year), and with higher UAS7 severity (p = 0.006). Although ClndU was associated with poor symptom control (p = 0.022), it was also associated with less exacerbations requiring medical observation or hospitalization (p = 0.015). All patients were using antihistamines and 21.3% (n = 13) of them were also under treatment with omalizumab, ciclosporine or montelukast for disease control.ConclusionsAutoimmunity can affect about half of the patients with severe or long-term CU. UAS7 and angioedema are associated with disease exacerbations. UAS7 and UCT presented unequal accuracy, with UAS7 better associating with the occurrence of exacerbations and treatment doses. Patients with refractory CU frequently present psychiatric disorders. Accurate diagnostic tests, namely autoimmune parameters and inflammatory markers, should be recommended in some individual cases.

Women with Autoimmune Thyroiditis have Lower Reproductive Life Span or Not? A Cross- Sectional Study.

ABSTRACTBackground: Autoimmune diseases are a main cause of primary ovarian insufficiency. This study was designed to elucidate the relationship between ovarian reserve and anti-thyroid peroxidase antibodies in women of different ages.Methods: 98 women in a cross-sectional study was conducted at the infertility Center of Shiraz University of Medical Sciences, Hazrate Zeinab Hospital, from September 2018 to March 2019. Women with infertility and thyroid-stimulating hormone (TSH) > 3mIU/L were included in the study with convenience sampling. Data were collected by a form containing demographic characteristics, thyroid hormones, and ovarian reserve data. Participants were categorized based on the negative or positive anti-thyroid peroxidase (anti-TPO) antibodies. According to a pilot sample, and possible dropout of 20%, the sample size was determined to be 49 cases in each group. The results were compared between groups using SPSS, version 22. All statistical comparisons were performed using the t-test, and the data are presented as the mean±SD. P-values less than 0.05 were considered significant.Results: 49 women were analyzed in each group. There was no significant difference between the groups in the mean age (P=0.42), body mass index (BMI) (P=0.34), duration of infertility (P=0.99), mean prolactin (P=0.66), TSH (P=0.17), thyroxine (T4) (P=0.87) and follicle-stimulating hormone (FSH) levels (P=0.14). Ovarian reserve characteristics: antral follicular count (AFC) and anti-Müllerian hormone (AMH) levels in anti-TPO positive group were 10.61±7.29 and 1.98±2.38, respectively, and AFC and AMH in anti- TPO negative group were 16.46±6.38 and 2.94±2.22, respectively. There were significant differences between the two groups on AFC (P <0.001) and AMH (P=0.04). Conclusion: Patients with autoimmune thyroiditis were at higher risk for decreased ovarian reserve. They should consider their lower reproductive life span during their childbearing years.

A unique case of myxedema madness with suicidal attempts

Hypothyroidism has been associated with mood disorders, sometimes with acute psychosis, hence this report. A 45-year-old married female, working as a daily-wage laborer, was brought with marked irritability, suspiciousness, wandering about, decreased sleep, appetite, and personal care for the past 1½ years. She had attempted suicide three times in the initial 6 months of illness. She had an asthenic body type; dry, hairless skin; hoarse voice; and nonpitting pedal edema. Deep tendon reflexes were delayed. High thyroid-stimulating hormone levels and positive anti-thyroid peroxidase antibody led to the diagnosis of severe hypothyroidism. Based on her psychiatric evaluation, a diagnosis of organic schizophrenia-like disorder (myxedema madness) was made. She was managed with olanzapine and haloperidol along with thyroxine supplement. The patient improved significantly following thyroxine supplementation and modified electroconvulsive therapy sessions. Herewith, we present this unique case of myxedema madness with suicidal attempts for its uniqueness and rarity.

A study of Anti Thyroid Peroxidase (TPO) Antibody Titres in patients seeking treatment at a tertiary health care centre

Background: One of the main cause of thyroid disease is autoimmune thyroid disease and anti thyroid peroxidase (TPO) antibodies is a major marker of the condition. There are very few studies in the country regarding the etiology of thyroid disorders and hence this study is being conducted for it.&#x0D; Methods: This is retrospective cross sectional study from 28 January 2019 to 29 July 2019 done at National Academy of Medical Sciences, Bir Hospital, Kathmandu. The laboratory serum sample data of all Anti TPO antibody results from patients seeking treatment at the instituition were analyzed for age and gender variation. Anti TPO antibody titre of equal or more than 34 IU/ml was considered as positive.&#x0D; Results: Out of 768 samples analysed for study, 79.9% were of women and 20.1 % were of men. A total of 205 (26.7%) were positive for anti TPO antibodies of which 83.4% were women and 16.6% were men . Women had more patients with anti TPO antibodies positive as compared men (27.9 vs 21.1%). Mean Anti TPO titre were also more in women as compared to men (61.01 vs 48.20 IU/ml).&#x0D; Conclusions: About one fourth of the patients had siginificant titers of anti TPO antibodies suggestive of thyroid autoimmunity. Both prevalence of positive anti TPO antibody titres and the mean anti TPO antibody titre values were more in women as compared to men. Further well designed larger community studies are required.

A Literature Review of Painful Hashimoto Thyroiditis: 70 Published Cases in the Past 70 Years.

Painful Hashimoto thyroiditis (pHT) is a rare diagnosis, and optimal treatment remains unclear. To better characterize pHT, PubMed, Embase, Scopus, and Web of Science indexes were searched for case reports or case series reporting pHT, published between 1951 and February 2019. Seventy cases reported in 24 publications were identified. Female predominance (91.4%) and a median age of 39.00 years (interquartile range, 32.50-49.75 years) were observed. Among reported cases, 50.8% had known thyroid disease (including Hashimoto thyroiditis, Graves disease, and seronegative goiters), 83.3% had positive antithyroid peroxidase antibodies, and 71.2% had antithyroglobulin antibodies. Most cases did not have preceding upper respiratory tract symptoms or leukocytosis. Ultrasound features were consistent with Hashimoto thyroiditis. Thyroid function at initial presentation was hypothyroid (35.9%), euthyroid (28.1%), or thyrotoxic (35.9%). Cases evolved into hypothyroidism (55.3%) and euthyroidism (44.7%), whereas none became hyperthyroid after medical treatment. Thyroid size usually decreased after medical treatment. Most cases were empirically treated as subacute thyroiditis with corticosteroids, levothyroxine, or nonsteroidal anti-inflammatory drugs. However, no therapy provided sustained pain resolution. In subgroup analysis, low-dose oral prednisone (<25 mg/d) and intrathyroidal corticosteroid injection showed more favorable outcomes. Total thyroidectomy yielded 100% sustained pain resolution. Diagnosis of pHT is based on clinical evidence of Hashimoto thyroiditis and recurrent thyroid pain after medical treatment. The reference standard of diagnosis is pathology. Total thyroidectomy or intrathyroidal glucocorticoid injection should be considered if low-dose oral prednisone fails to achieve pain control.

MON-LB007 Incidence and Characteristics of Thyroid and Pituitary Dysfunction in Patients Treated with Immunotherapy

Background Endocrinopathies are well recognised immune-related adverse events associated with immunotherapy. Incidence rates of hypophysitis and thyroid dysfunction are widely variable in the literature. Hypophysitis has been reported in between 0.4% and 27% in patients treated with CTLA-4 inhibitors such as ipilimumab (1) while the incidence of thyroid dysfunction varies between 8% and 20% in patients treated with PD-1 inhibitors such as nivolumab and pembrolizumab (1). Aims Our aim was to determine real world rates of thyroid and pituitary dysfunction in patients treated with immunotherapy. We also sought to evaluate the characteristics of same-e.g. time to onset of adverse events and presence of autoantibodies. Methods A retrospective cohort study was performed in 347 patients who received treatment with PD-1 inhibitors nivolumab and pembrolizumab, anti-CD52 antibody alemtuzumab and CTLA-4 inhibitor ipilimumab between January 2013 and December 2017 at a tertiary referral metropolitan hospital in Melbourne, Australia. Patients were identified from pharmacy records and assessment of the clinical and biochemical records pertaining to thyroid function (TFT) and serum cortisol was performed. Results 45 patients (12.9%) had evidence of thyroid or pituitary dysfunction from the therapies. 34 of the 267 (12.7%) patients on PD-1 inhibitors developed thyroid dysfunction, 15 (5.6%) of whom had a clear thyroiditis picture-i.e. thyrotoxic phase with subsequent hypothyroidism. 3 of the 34 (8.8%) patients who received CTLA-4 inhibitor ipilimumab developed hypophysitis, all of whom were on combined treatment with a PD-1 inhibitor. Median time to onset of adverse effects was 30days. 12 out of 27 patients with thyroid dysfunction had positive anti-thyroid peroxidase antibodies. 25 of the 45 (55.6%) patients were reviewed in endocrine outpatient clinics. Only 2 of the 45 endocrinopathies were recorded in the hospital’s adverse drug reactions database. Conclusions In our tertiary centre, endocrinopathies are common in patients treated with immunotherapies; however reportage to the adverse drug reaction database is low and endocrinology services appear underutilised. Current guidelines suggest TFT monitoring every 4-6weeks on therapy (2) with baseline monitoring of early morning ACTH and cortisol concentrations to be considered in patients treated with CTLA-4 inhibitors. Greater clinician awareness and adherence to guidelines is needed for optimal patient care.