Positive anti-TPO Antibodies Research Articles

A study of autoimmune thyroid disease in pregnant women and its effect on fetal and maternal outcome

ABSTRACT Introduction: Anti-thyroid antibodies not only cause thyroid dysfunction but have independent adverse outcomes in the fetus and mother during pregnancy and after birth. Chronic lymphocytic thyroiditis as a presentation of immune system deregulation may be associated with a generalized activation of the immune system at the fetus–maternal unit, the placenta. This interference could be associated with pregnancy morbidities in m o t h e r a n d fetus. This study was done to find out the frequency of autoimmune thyroid disease and its effect on maternal and fetal outcomes in a tertiary care facility in Jharkhand. Method: This is an Observational Prospective Study done during an 18-month period on 254 pregnant women in their second trimester who came to the antenatal clinic (ANC) clinic with singleton pregnancy at RIMS Ranchi. Result: 222 (87.4%) out of the 254 pregnant women had anti- TPO antibodies less than 35 IU/ml. Anti-thyroid peroxidase (anti-TPO) antibody positivity with values greater than 35 IU/ml was found in 32 patients (12.6%). Anti-TPO antibody mean value was 22.54 ± 19.67 IU/ml. Among the 222 individuals who tested negative for the anti-TPO antibody, 7 (3.3%) had miscarriages, 182 (88.3%) gave birth vaginally, and 33 (14.9%) underwent a cesarean section. Of the 32 individuals who tested positive for the anti-TPO antibody, 2 (6.3%) had miscarriages, 24 (75.0%) had vaginal deliveries, and 6 (18.8%) had cesarean sections. Using the Chi-square test, a P value of 0.549 was calculated, indicating statistical insignificance (Pearson Chi-square test value = 0.200a). Conclusion: Anti-TPO antibody positivity was significantly related to miscarriage and anemia. Other complications like preterm delivery, pre-eclampsia, and low birth weight were higher in anti-TPO antibody-positive patients as compared to anti-TPO antibody-negative patients. However, these findings were not statistically significant.

6581 Case of Conversion from Hashimoto’s Thyroiditis to Graves’ Disease: An Unusual Sequence

Abstract Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: The two most common autoimmune thyroid diseases are Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). HT is a destructive thyroiditis, via autoantibodies most commonly against the thyroid peroxidase enzyme (anti-TPO), while GD results in hyperthyroidism, due to TSH-receptor stimulating antibodies (TSAb) and Thyroid Stimulating Immunoglobulin (TSI). Case Report: A 23-year-old male presented to the clinic with complaints of weight gain, dry skin and excessive hair loss. His physical examination was non-contributory and laboratory evaluation revealed a TSH of 130 uIU/ml (ref: 0.45-4.5), free T4 (fT4) 0.4 ng/dl (ref: 0.82-1.77), and positive anti-TPO antibodies, for which he was started on levothyroxine (LT4) supplementation for newly diagnosed HT. Over the first five months on treatment, his TSH and T4 progressively improved to 31.8 uIU/ml and 1.48 ng/dl, respectively. Six months later, his TSH rapidly decreased to 0.01 uIU/ml, with an fT4 elevation to 2.45 ng/dl, alongside developing hyperthyroid symptoms like weight loss, insomnia and palpitations. Due to persistently positive anti-TPO antibody titers, his hyperthyroidism was considered iatrogenic, and LT4 dose was gradually reduced, but eventually required to be discontinued. A thyroid ultrasound depicted generalized increase in vascularity, consistent with active thyroiditis. He continued to have a significantly suppressed TSH <0.005 uIU/ml and elevated fT4, off all medications, and was also found to have multiple positive antibody titers [TSI of 1.02 IU/L (ref: < 0.55), thyroglobulin antibody of 351 IU/ml (< 0.9) and anti-TPO Ab >600 IU/ml (ref< 34)]. He was then diagnosed with new GD, and thyroid suppression therapy with 10mg/day of methimazole was initiated, to which he rapidly responded, with a TSH of 0.059 uIU/ml and reduced fT4 of 1.37 ng/dl. His diagnosis of GD was confirmed via an I-123 thyroid uptake scan which revealed a homogenous increased tracer uptake of 57% at 24 hours (ref 15-35%), following which he received definitive therapy for GD, with radio-active iodine (RAI) ablation with 20.6 mCi of I-131. Discussion: As HT and GD have a common autoimmunity-based pathophysiology, conversions between the two clinical states have been described, though HT to GD, as seen in our patient is much less common than the reverse conversion. Some described mechanisms include an antibody switch from thyrotropin receptor blocking to stimulating action, HT-induced thyrotroph destruction resulting in GD antibody formation, and treatment with LT4. Simultaneously elevated levels of both TSI and anti-TPO can occur, and therefore treatment and diagnosis should be based on thyroid function tests and clinical presentation. Patients with autoimmune thyroid disease require close monitoring, due to the potential risk of conversion from one clinical end of the spectrum to the other, and early recognition is important. Presentation: 6/1/2024

6771 New onset Graves’ Disease in a Patient with Hashimoto's Thyroiditis and Positive Thyroid Peroxidase Autoantibodies. Case Report

Abstract Disclosure: M.M. Eid: None. J.L. Zapater: None. Introduction: Hashimoto’s Thyroiditis (HT) and Graves’ Disease (GD) are the most common thyroid autoimmune disorders. Transition of GD to HT is common, but transition of HT to GD is rare. Case: A 55 year old, female with depression, HTN and fibromyalgia. She was referred for evaluation of chronic fatigue and reduction in functional capacity. Five years earlier, she had also been evaluated for fatigue. Labs at that time: TSH 3.80 µIU/ml (0.35-3.74 µIU/ml), free T4 0.8 ng/dl (0.76-1.46 ng/dl), thyroid peroxidase antibody (anti-TPO) 605.6 U/ml (0-60 U/ml), and anti-thyroglobulin antibody (anti-TG) 37.2 U/ml (0-60 U/ml). Subclinical hypothyroidism was diagnosed, but no levothyroxine was initiated. Her TSH was found to be normal in 2019 and 2021. At the current clinical encounter, other than fatigue she denies weight/voice change, tremor, palpitation, anxiety, recent flu like illness or radiation exposure, neck swelling/pain, heat intolerance, or difficulty swallowing. Her daily medications are amlodipine 10mg and duloxetine 20mg. She had menopause 2 years ago. She has no known allergy. She has a brother with rheumatoid arthritis. She denies smoking or alcohol consumption. On exam, vital signs are normal, and BMI is 28.1. There is diffuse, firm thyromegaly without a palpable nodule. There is no cervical lymphadenopathy, tremor, neck tenderness, exophthalmos, or lid lag. Creatinine, liver enzymes are normal but hemoglobin is 9gm/dl. Anti-tissue transglutaminase and anti-gliadin antibodies were negative. Her thyroid labs were: TSH <0.008 uIU/ml, free T4 1.06ng/dl, free T3 4.07 pg/ml (2.3-4.2 pg/ml), total T3 1.74 ng/ml (0.60-1.81 ng/ml), anti-TPO antibody 12,414 U/ml, anti-TG antibody 22 U/ml, thyrotropin receptor antibody (TRAB) 15.24 IU/L (0-1.75 IU/L), and thyroid stimulating immunoglobulin (TSI) 331% (<130%). Thyroid uptake scan showed 49% iodine-131 uptake in symmetric and homogenous uptake, and no hot or cold nodules. GD was diagnosed, methimazole 5mg daily was initiated. Conclusion: Our case had subclinical HT with positive anti-TPO antibodies 5 years preceding the onset of GD. Causes of autoimmune conversion are not well understood. Viral infection or radiation exposure in genetic susceptible patients have been assumed as triggers (1). The blocking and stimulating action of TRAB on TSH receptors is considered as a possible mechanism of switching between hypothyroidism and hyperthyroidism. Clinical and biochemical evaluation for possible conversion to GD in patients with HT is recommended (2).

The prevalence of patients suffering from chronic spontaneous urticaria, in whom omalizumab cannot be stopped even after six years.

Omalizumab (OMA) was the first FDA-approved biological drug for severe chronic spontaneous urticaria (CSU), and until today is the only beneficial and truly safe one. The objectives were: To assess the prevalence of CSU patients in whom OMA cannot be stopped over time. We also asked if biomarkers (e.g., anti-TPO antibodies and total IgE) could assist in anticipating this issue. We used our prospective registry of 93 patients, which included CSU disease duration, the onset of OMA treatment, Urticaria Activity Score (UAS7) during follow-up, co-morbidities, serum IgE levels and the presence of anti-TPO antibodies. Finally, we assessed the response to OMA during a period of six years. Out of the 93 treated CSU patients, OMA was stopped in ten patients after six months being defined as failures. In another ten patients, OMA was discontinued after 2-4 years of therapy, achieving a remission. Seventy-three patients are still treated between 2 and 6 years, having different degrees of response. Of these, in thirty-eight (52%) patients, we could not stop OMA even after six years due to CSU relapses. The prevalence of lower serum IgE levels and anti-TPO antibody positivity was significantly higher in CSU patients in whom OMA could not be stopped. This is the first study where OMA-treated CSU patients were followed up to six years. In half of them, long-term therapy of six years is still required.

Factors affecting timing of hypothyroidism following radioactive iodine therapy (RAIT) for patients with Graves' disease: A 12-month observational study.

This retrospective study analyzed factors influencing hypothyroidism development after radioactive iodine therapy for Graves' disease. Three hundred and three patients with Graves' disease treated with radioactive iodine (RAI) from 2013 to 2022 at two Egyptian hospitals were included. Data collected included demographics, lab values, thyroid imaging, RAI doses, and outcomes. Patients were followed for ≥1 year to assess hypothyroidism onset. At the end of 1 year, around 79.5% of the individuals developed hypothyroidism while 12.5% continued to experience hyperthyroidism. The onset of hypothyroidism occurred earlier in those with thyroid volume (≤75.5 cm 3 ), lower thyroid weight (≤84.7 g), thyroid uptake (≤18.8%), and higher RAI dose/volume (≥0.1022 mCi/ml) ( P < 0.001). Additionally, there was a correlation between anti-thyroid peroxidase (anti-TPO) antibodies and faster development of hypothyroidism compared to those who were negative for antibodies (2.9 vs 8.9 months, P = 0.001). When considering factors in analysis it was found that anti-TPO antibodies were the only independent predictor, for developing hypothyroidism (hazard risk 30.47, P < 0.001). Additionally, thyroid volume and uptake independently predicted successful treatment outcomes ( P < 0.05). Positive anti-TPO antibodies strongly predict hypothyroidism risk after RAI therapy for Graves' disease. Smaller thyroid size, lower uptake, and higher RAI dose/volume correlate with earlier hypothyroidism onset but are less significant predictors than anti-TPO status. Findings can guide RAI therapy personalization to optimize outcomes.

Biochemical evaluation of thyroid hormone level in infertile women: A case control study

Introduction: Infertility in women is an important health problem which imposes psychological stress and affects the wellbeing of couples. Thyroid disorders is the most frequently encountered endocrine problem among the women in the age reproductive and it can lead to infertility and miscarriage. The objective of the study was to evaluate the thyroid hormone level in infertile women and compared to the healthy controls. Materials and methods: The study was conducted on 50 infertile women (cases) and 50 fertile healthy women (controls). Thyroid stimulating hormones (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and Anti-thyroid peroxidase (Anti-TPO) levels were estimated and compared between the cases and controls. Results: The mean TSH level was significantly higher in infertile women (cases) as compared controls (6.76±0.87 vs 2.54±0.12mIU/L; p=0.002).The prevalence of hypothyroidism among the infertile women in the present study was 28%. The anti-TPO antibody level was significantly higher was in infertile women as compared to controls (4.87±0.8 vs 2.32±0.05 IU/ml; p=0.000). In addition the number of positive Anti-TPO antibody cases was higher in infertile women as compared to controls (24% vs 4%; p=0.02). Conclusion: Therefore, women planning for pregnancy and infertile women must be evaluated for thyroid profile and if there are any abnormalities they should undergo proper treatment for better pregnancy outcome.

Subclinical hypothyroidism and anti-thyroid peroxidase antibodies in primary open-angle glaucoma: A case-control study.

To evaluate the association among subclinical hypothyroidism, anti-thyroid peroxidase (anti-TPO) antibody, and primary open-angle glaucoma (POAG). Case-control study. The cases consisted of patients with POAG and controls were age- and sex-matched patients from the general eye clinic with no history of glaucoma. Blood samples were taken from the participants' antecubital veins and sent for measurement of thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and anti-thyroid peroxidase (anti-TPO) antibody. Data was analyzed using the Mann-Whitney U test and the Chi-square test. Odds ratio with 95% confidence interval (CI) was calculated. A two-tailed P value less than 0.05 was considered for statistical significance. There were a total of 63 cases and 63 controls. Subclinical hypothyroidism was present in 20.6% of patients in the glaucoma group and 4.8% of patients in the control group ( P < 0.01). The odds of subclinical hypothyroidism in patients with POAG compared to controls was 5.2 (95% CI 1.7-22). Anti-TPO antibody positivity was higher in the glaucoma group (22.2%) than in the control group (14.3%), but this did not reach statistical significance ( P = 0.25). This study suggests an association between POAG and subclinical hypothyroidism. Further research is needed to establish the cause-and-effect relationship between these two conditions.

Efficacy and Safety of Recombinant Thrombopoietin Combined with Immunosuppressive Therapy for Primary Treatment of Severe Aplastic Anemia: A Single-Center, Open-Label, Randomized, Clinical Trial

Standard immunosuppressive therapy (IST) combined with eltrombopag is the first-line treatment regimen for severe aplastic anemia patients who are ineligible for allo-hematopoietic stem cell transplantation (allo-HSCT). However, there was no second-generation TPO receptor agonist available in China before 2019, and only a first-generation TPO preparation was available for clinical treatment. Although rhTPO and eltrombopag act on different receptor binding sites, the differentiation pathways are similar, so rhTPO can theoretically also stimulate hematopoietic stem cells and promote hematopoietic recovery in AA. In 2015, we used rhTPO combined with IST as the first-line treatment for SAA. The results showed that the OR and quality of response in the rhTPO group were significantly higher than those in the control group. Multivariate analysis showed that the application of rhTPO was an independent prognostic factor affecting the efficacy of IST. Based on these results, we performed a single-center, randomized, open-label, parallel-controlled clinical trial to assess the hematologic response rate and long-term safety 3, 6, and 12 months after treatment. The study was conducted between 2015 and 2019 with 188 patients with primary SAA who were randomly assigned to the control or rhTPO group (95 with IST alone and 93 with rhTPO). For rhTPO, 15000 IU was administered subcutaneously starting on day 14 after p-ATG administration and then once every other day for a total of 14 injections. The median age of the 93 patients in the rhTPO group was 33 years (range 16-67). These included 58 patients with SAA and 35 patients with very severe aplastic anemia (VSAA), which were comparable to the control group. There were no significant differences in baseline clinical parameters between groups. No significant differences were observed in the overall hematologic response rates at 3, 6, and 12 months between the rhTPO and control groups (3 months: 40.9% vs 41.1%, P = 0.979; 6 months: 52.7% vs 52.6%, P = 0.994; 12 months: 65.6% vs 63.2%, P = 0.782, respectively). The median time of platelet transfusion independent was 49 (0-376) days in the rh-TPO group and 47 (0-195) days in the control group, which was not different between the two groups ( P = 0.757). The median time of RBC transfusion independence was 47 (5-404) days and 49 (0-295) days, respectively ( P = 0.592). The median follow-up time was 64 (1.3-86.2) months. The 5-year overall survival was 86.4% (95% confidence interval [CI], 77.2-92.0%) in the rh-TPO group and 84.1% (95% CI, 74.5-90.3%, P = 0.898) in the control group. The 5-year event-free survival was 51.7% (95% CI, 41.0-61.5%) and 54.1% (95% CI, 43.5-63.6%, P = 0.947) in the two groups, respectively. No significant differences were observed in the relapse rate and clonal evolution rate between the two groups (11.5% vs. 11.7%, 4.3% vs.3.2%, repectively). Subcutaneous rhTPO injection was well tolerated by patients, with no significant adverse effects other than mild localized pain at the injection site. The patients in the rhTPO group did not have concomitant thrombotic or embolic complications; moreover, reticulo-fibrillary or collagen fibrillary hyperplasia in bone marrow was not detected in any patients at three and six months after IST. Ten patients had anti-TPO antibodies at the end of TPO treatment, with no positive anti-TPO antibodies. In conclusion, our study is the only prospective randomized controlled clinical trial in China of rhTPO combined with IST for the treatment of SAA, with no difference in the hematologic response rate of the 28-day rhTPO combination regimen compared to standard IST; however, we did confirm the safety of rhTPO at this dose. Further clinical studies are required to determine the most effective dosage and duration of rhTPO treatment.

Do elevated thyrotropin levels increase the risk of miscarriages: yes or no?

Background To examine correlation between elevated levels of thyrotropin with the frequency of miscarriages. Methods A cross-sectional study was conducted on the 380 respondents and it investigated TSH (thyrotropin), thyroid peroxidase antibody(anti-TPO) and free thyroxine (FT4) in pregnant women who had a miscarriage (N = 179) and pregnant women with normal pregnancies (N = 201). Results The incidence of subclinical hypothyroidism in the miscarriages group was higher than in control group (61.4% vrs 15.79% (p < 0.001). In the miscarriages group with hypothyroidism (first trimester) mean value of TSH was significantly higher 4.31 ± 2.55 mIU/L compared to the control group 1.95 ± 0.86mIU/L (p < 0.001). Logistic multivariate regression revealed that TSH and body mass index (BMI) have a significant influence on the miscarriage; TSH level has a higher odds ratio (OR) 1.47 CI (95% 1.22–1.78) than BMI (OR) 1.14 CI (95% 1.06–1.23)) (p < 0.001). The combination of thyroid autoimmunity and TSH > 2.5mIU/L increase the risk of miscarriage (65.75%) compared to positive anti-TPO antibodies and TSH < 2.5mIU/L(14.15%)(p < 0.001). Conclusions Higher TSH levels correspond with obesity during early pregnancy and may be a sign of maternal thyroid dysfunction. Physiological thyroid function in the first trimester of pregnancy is important for perinatal outcome.

THU237 A Case Of Primary Hypothyroidism, Dysglycemia And Epilepsy With PAX8 And SETD1A Mutation

Abstract Disclosure: S.K. Singh: None. KEYWORDS: PAX8, SETD1A, DYSGLYCEMIA INTRODUCTION: Hypothyroidism is associated with dysglycemia linked with insulin resistance and shared common genetic determinants.PAX 8 gene regulates the development of thyroid gland as well as the expression of TG,TPO and NIS genes.It impacts glucose homeostasis by favoring beta-cell survival and through thyroid hormones.Epilepsy in hypothyroid patients can be idiopathic or due to Hashimoto’s Encephalopathy (HE). Thyroid hormones can impact epileptogenesis through mitochondrial dysfunction, oxidative-stress and GABAergic transmission. THE INDEX PATIENT: A 13 year old female(weight and height age 1.5 years below her chronological age by Indian growth chart and a further lag of 18 months and 6 months, respectively by CDC chart)was diagnosed as a case of thyroprivic hypothyroidism with TSH - 100 mIU/L and positive anti-TPO antibody. She was euthyroid on 112 ug/d L-T4.She is on anticonvulsant since 12 years of age for tonic-clonic epilepsy. The MRI of brain showed focal gliosis with few small encephalomalacic streaks in right occipital lobe. On evaluation at 12.5 years of age, her fasting plasma glucose was 80 mg/dl and her HbA1c was 4.8% but 2-h post glucose was 233 mg/dl with another value of 270 mg/dl. Her father has T2DM and Hypothyroidism. Her mother is Hypothyroid. Her genetic study showed SETDIA and PAX8(-) mutations. DISCUSSION: PAX8 regulates development of thyroid gland and biosynthesis of thyroid hormones. It can impact glucose homeostasis by enhancing beta-cell survival by inhibiting apoptosis, immunomodulation, maintaining local anti-inflammatory milieu in pancreas, ensuring systemic levels of thyroid hormone to stimulate insulin secretion and protect beta-cells from environmental stressors.PAX8 mutation in a family has been shown to be associated with a spectrum of disorders encompassing Gestational Thyroid Dysfunction(GTD),Gestational Diabetes Mellitus(GDM) and T2DM.[1] Although mutation analysis was done only in the index patient, Hypothyroidism and Dysglycemia (post- glucose&amp;gt;200 mg/dl)in the patient and family history of Hypothyroidism and T2DM could be linked with PAX8 mutation.SETD1A mutation has been linked with early-onset epilepsy with or without developmental delay. The mutation study can aid in deciding appropriate therapy including steroids for HE. CONCLUSION: This case highlights the significance of evaluation for PAX8 mutation in hypothyroid patients, even if anti-TPO positive, particularly when there is family history of thyroid dysfunction, GDM, T2DM. It also underlies the importance of SETD1A mutation analysis in hypothyroid patients with epilepsy. Presentation: Thursday, June 15, 2023

The association between thyroid dysfunction, autoimmune thyroid disease, and rheumatoid arthritis disease severity

BackgroundRheumatoid Arthritis (RA) and autoimmune thyroid disease (AITD) are the two most prevalent coexisting autoimmune diseases due to their similar pathogenesis. Considering the potential effect of AITD on the severity of RA disease, this study aimed to determine the association between thyroid dysfunction, anti-thyroid peroxidase (anti-TPO) positivity, AITD, and RA disease severity in the Iranian population.MethodsThree hundred and fifty RA patients who presented to Shahid Beheshti tertiary care center, Qom, Iran, were included in this cross-sectional study. The data were collected through the patient’s medical records, interviews, physical examinations, and laboratory tests. The RA disease activity score in 28 joints for RA with erythrocyte sedimentation rate (DAS-28-ESR) was used to divide patients into three subgroups, remission (DAS-28-ESR ⩽ 2.6), mild-to-moderate (2.6 < DAS-28-ESR ⩽ 5.1), and severe disease activity (DAS-28-ESR > 5.1).ResultsUsing the aforementioned method, 111, 96, and 138 patients were put into remission, mild-to-moderate, and severe disease activity groups, respectively. Anti-TPO antibody positivity rate was 2.93 times more prevalent among patients with severe disease compared to the remission subgroup (OR: 2.93; P-value < 0.001). Patients suffering from a more severe disease were almost 2.7 times more probable to have AITD (OR = 2.71; P-value < 0.001) and they were 82% more likely to have thyroid dysfunction compared to patients in remission (OR = 1.82; P-value = 0.006).ConclusionsIt was demonstrated that thyroid dysfunction, anti-TPO antibody positivity, and AITD were significantly more common among RA patients with more severe disease activity.

THU348 Thyroid Dysfunction And Diabetes In Pregnancy - Is There A Link?

Abstract Disclosure: R.K. Sahay: Speaker; Self; Novo Nordisk, Roche Diagnostics. S.A. Kalam: None. N. Kudugunti: Speaker; Self; Novo Nordisk. S. Togarla: None. Background: The Indian subcontinent has shown higher prevalence for both thyroid dysfunction and diabetes complicating pregnancy when compared to the Western population. The association between both has been studied in multiple small studies which have however shown discordant results. Hence the need for exploring this further. Aims: To assess the proportion of women with thyroid autoimmunity and thyroid dysfunction in pregnancy complicated by diabetes mellitus and determine association of the same with diabetes in pregnancy and maternal and perinatal outcomes. Methods: 150 pregnant women with gestational/pregestational diabetes were enrolled in this cross sectional study and the proportion of those with thyroid dysfunction were assessed. Thyroid autoimmunity was evaluated in the same population using antiTPO and anti-thyroglobulin antibodies. The proportion of women with thyroid autoimmunity as well as thyroid dysfunction was calculated and the association of these with diabetes in pregnancy was evaluated along with maternal and perinatal outcomes. The same tests were done on 26 pregnant women without diabetes who served as controls. Results: The mean age of the study population was 26.62 ± 4.34 years. 56% were diagnosed with GDM and the rest had pre-GDM. 26.6% of the study population were diagnosed with hypothyroidism. Of these,45% were newly diagnosed during the current pregnancy. The prevalence of antiTPO antibody positivity was found to be 9.33% whereas that of anti-thyroglobulin antibody was 3.33%. Maternal and perinatal complications were higher in the group with combined endocrinopathy with gestational hypertension and preterm delivery showing statistically significant increase among the latter group. Among those women with combined endocrinopathy who developed gestational hypertension,76.9% had GDM. All of them were found to have subclinical hypothyroidism which was newly diagnosed in third trimester. Conclusion: The prevalence of hypothyroidism in pregnancy complicated by diabetes is higher than the prevalence in normal pregnancy. Undiagnosed subclinical hypothyroidism was found to be strongly associated with development of gestational hypertension. Our study emphasises the fact that women with diabetes in pregnancy should receive early and periodic screening for thyroid dysfunction in pregnancy. Presentation: Thursday, June 15, 2023

Achievements in Hypothyroidism Treatment with Herbal Medicine: A Systematic Review of Randomized Controlled Trials.

Background Hypothyroidism is a common endocrine disease in the world that causes morbidity and mortality due to its association with metabolic diseases, especially in old age, and long-term treatment with levothyroxine causes many side effects for patients. Treatment with herbal medicine can regulate thyroid hormones and prevent side effects. Objective The purpose of this systematic review is the evaluation of the effect of herbal medicine on the signs and symptoms of primary hypothyroidism. Method PubMed, Embase, Google Scholar, Scopus, and Cochrane Central Register of Controlled Trials were searched until 4 May, 2021. We selected randomized clinical trials (RCTs) that have assessed the effect of herbal medicine on hypothyroidism. Result Out of 771 articles, 4 trials with 186 participants were included. In one study, Nigella sativa L. caused a significant decrease in weight (P=0.004) and body mass index (BMI) (P=0.002). TSH levels were reported to be decreased and T3 increased in the treatment group (P =0.03) (P=0.008), respectively. In another study on Nigella sativa L., results did not show a significant difference between the two groups (p=0.02). A significant decrease in total cholesterol (CHL) and fasting blood sugar (FBS) was reported in participants with negative anti-thyroid peroxidase (anti-TPO) antibodies. In patients with positive anti-TPO antibodies, a significant increase in total cholesterol and FBS was observed in the intervention group (p=0.02). In the third RCT, T3 in the ashwagandha group at 4 and 8 weeks significantly increased by 18.6% (p=0.012) and 41.5% (p < 0.001), respectively. A noticeable increase was found in the T4 level from baseline by 9.3% (p= 0.002) and 19.6% (p < 0.001) at 4 and 8 weeks, respectively. TSH levels fell remarkably in the intervention group compared to placebo at 4 weeks (p <0.001) and 8 weeks (p <0.001), respectively. In the last article selected, Mentha x Piperita L. showed no significant difference in fatigue scores between intervention and control groups at the midpoint (day 7), while fatigue scores improved in the intervention group in all subscales compared to the control group on day 14. Conclusion Some herbal remedies, including Nigella sativa L., ashwagandha, and Mentha x Piperita L., can improve the signs and symptoms of primary hypothyroidism, but using a more extensive and advanced methodology will provide us with more complete results.

STUDY AND CORRELATION OF ANTI THYROID PEROXIDASE ANTIBODY AND ULTRASONOGRAPHY FINDINGS OF THYROID IN PATIENTS OF THYROID DISEASES

Aim: To determine Anti thyroid peroxidase antibody and ultrasonography features of thyroid gland in thyroid disorder patients and study their correlation. Design: This is an observational, cross sectional study and techniques used are clinical and non-invasive. Method: Thyroid function tests, Anti-thyroid peroxidase (Anti-TPO)antibody and ultrasonography neck were performed in 150 patients .Eligible participants were adults of age group 15-70 years with deranged thyroid function tests . Pregnant patients and patients already on thyroid medications were excluded from the study The participants were classified as overt , subclinical hypothyroid or overt, subclinical hyperthyroid. Anti thyroid peroxidase antibody and ultrasonography neck findings obtained were analyzed and correlated using statistical methods. Statistical Analysis: Frequency and percentage were calculated and test of significance such as Chi square test, T test were used. Correlation was assessed using Spearmans correlation coefficient p=&lt;0.05 is considered significant. Result: From January 2020 to August 2021, 150 patients participated in the study in which 50%(n=75) patients were found to be subclinical hypothyroid, 21.3%(n=32) were overt hypothyroid, 21.3% (n=32) were overt hyperthyroid , 6% (n=09) were subclinical hyperthyroid and 1.3%(n=2) were euthyroid with thyroid swelling. 51.3%(n=77) patients had diffuse thyroid disease on ultrasonography neck, normal gland in 19.3%(n=29) patients, thyroiditis in 11.3%(n=17) patients ,Multinodular goiter in 10.6%(n=16) patients, nodule in 6%(n=09) and atrophic gland in 1.34%(n=02) patients. Anti thyroid peroxidase was positive in 62%(n=93) patients. Among patients with diffuse hypoechogenecity on ultrasonography 85%(n=80) patients had positive Anti-TPO antibody with p value 0.05. Conclusion: Maximum number of patients with thyroid diseases had a positive Anti thyroid peroxidase antibody that suggests autoimmunity as a major etiology of thyroid disease.Among patients with diffuse hypogenecity on USG,85%(n=80)patients had positive Anti-TPO antibody with statistical significance(p 0.05). Ultrasonography neck is non invasive ,safe and cost effective method to ascertain the cause of thyroid disease and has a major role in predicting prognosis of the disease. Abbreviations: Anti thyroid peroxidase antibody-Anti-TPO antibody Ultrasonography-USG.

A Curious Case of Cocaine-Induced Hypokalemic Periodic Paralysis Mimicking Guillain-Barre Syndrome (P10-5.003)

<h3>Objective:</h3> To describe a rare cause of progressive ascending paralysis resembling Guillain-Barre Syndrome (GBS). <h3>Background:</h3> Cocaine inhibits the reuptake of monoamines at the synaptic cleft to prolong sympathetic output. This adrenergic hyperresponsiveness mimics thyrotoxicosis as it replicates sodium/potassium ATPase hyperactivity, causing a cellular influx of potassium (hypokalemia), hyperpolarization, and sodium channel inactivation that presents as sudden, painless muscle weakness and paralysis. <h3>Design/Methods:</h3> Consent obtained from patient. <h3>Results:</h3> A 30-year-old female with no past medical history was evaluated in the ED for acute lower extremity weakness that ascended to the upper extremities within &lt; 12 hours. Labs were significant for hypokalemia at 1.6, elevated inflammatory markers, elevated Free T4 at 2.58, and low TSH at &lt; 0.015. Urine drug screen was positive for cannabis and cocaine. Serum toxicology was negative. MRI of the T-spine and L-spine were unremarkable. Lumbar puncture was unremarkable. Cranial nerves were intact. Strength was 1/5 throughout, including at the neck. Flaccid tone. Lower extremity reflexes were 2+. Negative Babinski. Positive Hoffman bilaterally. Preserved sensation. The patient was admitted to the ICU, intubated for impending respiratory distress, and treated with IVIg. MRI of the C-spine was unremarkable. Further labs demonstrated elevated Free T3 at 7.13 and positive anti-TPO antibodies, significant for Grave’s disease. Urine labs were substantial for distal RTA. Anti-SSA and SSB antibodies were positive, indicating likely Sjogren’s syndrome (SS). Ganglioside panel was negative. Potassium was aggressively repleted. By day 1, the patient was moving all four extremities, and IVIg was discontinued. By day 2, she was successfully extubated. She was ambulating without difficulty on discharge. <h3>Conclusions:</h3> Secondary hypokalemic periodic paralysis may mimic Guillain Barre syndrome (GBS), a life-threatening demyelinating neuropathy that presents as rapidly progressive, symmetric, ascending paralysis or paresthesia with loss of reflexes. In our case, cocaine was the most plausible trigger for hypokalemia. <b>Disclosure:</b> Dr. Baumann has nothing to disclose. Dr. Rizvi has nothing to disclose. Ms. Alayon has nothing to disclose. Mr. Kendall has nothing to disclose. Dr. Shaffer has nothing to disclose. Dr. Mouhanna has nothing to disclose. Dr. Kenniff has nothing to disclose.

Association between antithyroid peroxidase antibody and recurrent miscarriage.

Thyroid disease is the second most commonly affected disease in childbearing women, after diabetes, and thyroid autoimmunity in pregnancy has been connected with adverse pregnancy outcomes such as miscarriage, recurrent miscarriage, preterm birth, and low IQ. The study seeks to determine the correlation between anti-thyroid peroxidase antibodies and unexplained recurrent miscarriage. 124 women were included in this case-control study, divided into 62 women who have experienced unexplained recurrent miscarriages and 62 healthy women without a history of miscarriage. Screening for TSH and anti-TPO antibody were done for both groups. The prevalence rate of positive anti-TPO antibody in women with recurrent miscarriage was 19.4%, while in women without miscarriage was 6.5% (which is considerably higher in cases than in women without recurrent miscarriage with a p-value of 0.03 and an odd ratio of 3.48 (95% CI; 1.06-11.48). A statistically significant relationship between anti-TPO antibodies and recurrent miscarriage has been detected. We recommend screening for TSH and thyroid antibodies for women with recurrent miscarriages and further studies on the effect of levothyroxine therapy for euthyroid women with antibody positive.

A Rare association of Mauriac syndrome and Van-Wyk Grumbach syndrome found in a young Saudi girl with poorly controlled type 1 Diabetes and Hypothyroidism: A Case Report and Brief literature review

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insufficient insulin production of the pancreatic beta-cells. Patients with T1DM will have a higher risk of other autoimmune disorders like celiac and thyroid diseases. Hypothyroidism is the failure of the thyroid gland to secrete an adequate amount of thyroxine, which is required for physical growth, brain development, and cellular metabolism. Most studies reported that children with T1DM have a higher incidence of hypothyroidism than normal children, with 9.6% having hypothyroidism and 19% having positive anti-TPO antibodies. Hypothyroidism will aggravate the condition in a child with T1DM and vice versa. Uncontrolled diabetes for a long time might increase insulin resistance due to complete depression of the hypothalamus-pituitary thyroid axis. A rare complication of poorly controlled T1DM is Mauriac syndrome, characterized by elevated liver enzymes, hyperlipidemia, cushingoid features, growth retardation, and hepatomegaly due to glycogenic hepatopathy. Van Wyk–Grumbach syndrome is also a rare complication of long-standing, untreated hypothyroidism, manifested by breast development, multicystic ovary, uterine bleeding associated with lack of pubic and axillary hair growth, and delayed bone age. Here, we report a case with two rare complications of Mauriac syndrome and Van Wyk–Grumbach syndrome in a child with hypothyroidism and poorly controlled T1DM.

O-149 Personalized probiotics and food supplementation according to microbiome miRNA test improves the conception rate in multiple IVF failure patients

Abstract Study question Can the microbiota play a role in the development of infertility by affecting the epigenetic, immunologic, and/or biochemical functions of the host? Summary answer The customization of diet and a nutraceutical and probiotic supplementation according microbiome miRNA signature could increase the pregnancy and live birth rates. What is known already The normal gut microbiota has an impact on the normal function of the male and female reproductive tract by regulating the immunological changes associated with conception. Several miRNAs -a class of small noncoding RNA molecules that control gene expression at the post-transcriptional level- have been described to be associated with dysbiosis and an immune imbalance. We previously demonstrated that women with unexplained infertility could have a gut and vaginal microbiome imbalance with increased intestinal permeability linked to an overexpression of miR-21 and miR-155. Study design, size, duration Observational study including 287 multiple IVF failure infertile patients. They had an average age of 40y and they performed 4 IVF-ET within 10 years on average. Swab samples were collected from the vagina and rectum. Participants/materials, setting, methods Microbial composition by NGS and miRNA expression by real time PCR of vaginal and rectal samples were measured. Immunometabolic markers from blood (TPO, vitamin D and B12, insulin, LDL) were analyzed. Patients followed a customized food supplementation, according to the tested biomarkers, for 90 days. Main results and the role of chance We found that 80% of women showed increased miRNA levels associated with gut and vaginal microbiome imbalances. Deficient values of Vitamin D and/or B were found in 73.2% of tested patients, whereas 56.1% showed high LDL and or insulin values and 19.9% showed positive anti thyroid TPO antibodies. Based upon the elevated levels of miRNAs and immunometabolic markers (insulin, vitamin D, autoantibodies, LDL cholesterol and secretory IgA), patients completed a 60-90 day therapy prior to their next IVF-ET attempt with no clinical side effects. BMI measurements before and after the therapy were not significantly different. After normalization of the blood biomarkers, each patient underwent a next IVF -ET attempt. The total pregnancy rate resulted in 75% (215/287) of positive chemical pregnancy (hCG) and 73% (157/215) of clinically confirmed pregnancy (ultrasound). The live birth rate per intended egg retrieval (all embryos transfers) was 60% (129/215); 27 pregnancies resulted in first trimester losses and one fetal death after a severe preeclampsia. Limitations, reasons for caution A future study should be performed testing miRNA expression before and after the food supplementation to achieve a direct correlation between the microRNA test and the supplementation in a placebo control study in order to evaluate the efficacy of the personalized supplementation on improving pregnancy and live birth rates. Wider implications of the findings Immune system and microbiome modulation could be adress by customizing different strains of probiotics and nutraceuticals selected for their immunomodulatory capacity. An anti-inflammatory dose-specific effect to maintain a delicate immune balance and favor endometrial mucous vascularization and the subsequent placentation, should be personalized to achieve a healthy pregnancy. Trial registration number CEI 1590

Cord blood metabolomics reveals gestational metabolic disorder associated with anti-thyroid peroxidase antibodies positivity

BackgroundThyroid disease is one of the common endocrine disorders affecting the pregnant women, in which thyroid autoimmunity can alter the progress and the outcome of pregnancy. Women with euthyroid status but anti-thyroid peroxidase (anti-TPO) antibodies positivity before pregnancy are prone to subclinical gestational hypothyroidism. However, the connections between anti-TPO antibodies positivity and gestational hypothyroidism remain largely unknown. The aim of the present study is to investigate the differences of fetal metabolic profile at birth according to maternal anti-TPO status.MethodsWe performed 1H-NMR metabolomics on cord blood of a nested case control cohort of 22 pregnant women with matched thyroid hormone levels and demographic data, including 11 women with euthyroid status but anti-thyroid antibodies positivity (into the anti-TPO antibodies positivity group) and 11 matched women as controls with euthyroid status and negative anti-thyroid antibodies (into the control group).ResultsDistinct metabolic profiles were observed between the anti-TPO antibody positivity group and the nested control group, from which a total of 10 metabolites with between-group altered abundances were structurally identified. Five out of the 10 metabolites were up-regulated in the anti-TPO antibodies positivity group, including D-Glucose, L-Glutamine, 3-Hydroxybutyric acid, Myo-Inositol, Creatinine. The other 5 metabolites were down-regulated in the anti-TPO antibodies positivity group, including L-Leucine, L-Lysine, L-Glutamic acid, L-Tyrosine, and L-Phenylalanine. All the 10 metabolites have been previously reported to be correlated with hypothyroidism. Metabolite set enrichment analysis and pathway analysis suggested that amino acid metabolism pathways (especially the phenylalanine metabolism) were associated with anti-TPO antibodies positivity.ConclusionThe results of this study suggested that fetal metabolic disorder is correlated with anti-TPO antibodies positivity, representing by abundance alteration of hypothyroidism associated metabolites and the related disturbance of amino acid metabolism pathways.

Short-Term Adverse Pregnancy Outcomes in Women with Subclinical Hypothyroidism: A Comparative Approach of Iranian and American Guidelines

Introduction Subclinical hypothyroidism during pregnancy can be associated with numerous adverse outcomes. The purpose of this study was to compare short-term adverse pregnancy outcomes in treated versus nontreated patients who fall within the numerical range of thyroid-stimulating hormone (TSH) between the Iranian and American reference ranges. Materials and Methods Eighty pregnant women with a known level of antithyroid peroxidase (anti-TPO) and TSH levels of 2.5–3.9 mIu/L in the first trimester and 3–4.1 mIu/L in the second and third trimesters were enrolled in the study and randomly assigned into two groups including 41 patients in the intervention group and 39 in the control group. The intervention group was treated with levothyroxine at least 50 μg/day and the control group received no treatment. The data were analyzed by SPSS software version 23. Results The only significant findings were a correlation between pregnancy loss frequency (p − 0.011) and/or increased TSH level in the follow-up period (p = 0.008) with anti-TPO antibody positivity. Forty-four percent of mothers with positive anti-TPO Ab needed treatment initiation with levothyroxine, based on Iranian guidelines, due to increased TSH level during the follow-up period. Conclusion Untreated pregnant women with subclinical hypothyroidism, who were placed in the intermediate range of TSH, recommended by Iranian and American guidelines, did not show any significant difference in short-term adverse pregnancy outcomes compared to the treated patients. Positive anti-TPO Ab may play a role in the development of short-term complications in mothers with subclinical hypothyroidism or it may increase the likelihood of an increase in TSH level during pregnancy.