Thyroid Status Research Articles

The impact of CTLA-4 gene polymorphism on the content of organ-specific antibodies in patients with autoimmune thyroiditis among the population of Azerbaijan

BACKGROUND: The risk of developing immune tolerance to self-antigens in autoimmune thyroiditis is largely associated with a mutation in the CTLA-4 gene, the product of which negatively regulates T-cell activity. AIM: To study the A49G (rs231775) CTLA-4 polymorphism in patients with autoimmune thyroiditis in a sample of Azerbaijani residents and the effect of the frequency of identified alleles and genotypes on the level of antibodies to thyroid peroxidase and thyroglobulin. MATERIAL AND METHODS: A study was conducted in 2021–2023 involving 170 patients with autoimmune thyroiditis and 65 individuals without thyroid pathology or other autoimmune diseases, who formed a comparison group. The groups were matched by gender and age. Based on the patient history, thyroid status study results, thyroid ultrasound data, and organ-specific antibody assessment, the patients were diagnosed with autoimmune thyroiditis. The routine thyroid status study results in the comparison group were within normal limits. Genotyping of the A49G (rs231775) polymorphism was performed using polymerase chain reaction followed by digestion of the reaction product with PspEI restriction endonuclease. The results of the quantitative studies were presented as the median (Me) and interquartile range (25th quartile; 75th quartile). The correspondence of genotype frequencies to the Hardy–Weinberg equilibrium was assessed using the χ2 criterion. RESULTS: The results revealed a statistically significant increase in the frequency of the G allele (48%) compared to the control group [33.8%; p=0.039, χ2=4.27, odds ratio (OR) 1.865, 95% confidence interval (CI) 1.028–3.382] and a decrease in the frequency of the A allele (51.2%) relative to the control group (66.1%; p=0.0389, χ2=4.27, OR=0.536, CI=0.296–0.973). In 22.4% of patients with the GG genotype (p=0.005, χ2=7.86, OR=0.237, 95% CI=0.088–0.635) and 55.6% of patients with the G allele (p=0.0012, χ2=10.43, OR=0.360, 95%, CI=0.192–0.674), thyroglobulin antibody titers were more than 100 IU/ml. Thyroid peroxidase antibody levels of 100 IU/ml or more were recorded in 22.7% of study participants with the GG genotype (p=0.030) and 50.0% with the G allele (p=0.048). CONCLUSION: Elevated titers of antibodies to thyroid peroxidase and thyroglobulin were detected in patients from the population of Azerbaijan with the G allele and homozygous genotype GG of the +49A/G polymorphism of the CTLA-4 gene.

Correlation of thyroid function and sensitivity to thyroid hormone with spinal bone mineral content, bone mineral density, and osteoporotic vertebral fracture: A cross-sectional study based on NHANES.

Previous studies have demonstrated that thyroid hormone plays an important role in normal bone development, bone metabolism, and establishment of peak bone mass. However, the correlation of thyroid status with bone mineral content (BMC), bone mineral density (BMD), and osteoporotic vertebral fracture (OVF) is rarely discussed. The current study probes into the potential association between thyroid status and spinal BMC, BMD, and OVF from a novel perspective of thyroid function (TF) and sensitivity to thyroid hormone based on the National Health and Nutrition Examination Survey database. A total of 1844 participants were included in this study. The association of thyroid status with outcome variables, like spinal BMC, BMD, and OVF, was analyzed using thyroid function indices and sensitivity to thyroid hormone indices as influence factors. The correlation of them were assessed using univariate and multivariable weighted linear regression, weighted logistic regression models, restricted cubic spline model, and subgroup analyses. The results of this study showed that the association of free triiodothyronine (FT3)/free thyroxine (FT4) with BMC remained negatively associated after adjustment for all covariates. Higher thyroid peroxidase antibody (TPOAb) was significantly associated with an increased risk of developing OVF in both unadjusted and adjusted models. In addition, the results of the restricted cubic spline model were consistent with the weighted multivariate regression analysis after adjustment. The results of this cross-sectional study showed that higher FT3/FT4 and TPOAb were associated with decreased spinal BMC and the increased risk of OVF, indicating a complex link between thyroid status and bone health. Therefore, patients with hyperthyroidism, hypothyroidism, autoimmune thyroid disease, or abnormal peripheral thyroid sensitivity, especially who with elevated TPOAb or FT3/FT4, should focus on the prevention of vertebral osteopenia, osteoporosis, and OVF.

A SIMBA CoMICs Initiative to Cocreating and Disseminating Evidence-Based, Peer-Reviewed Short Videos on Social Media: Mixed Methods Prospective Study.

Social media is a powerful platform for disseminating health information, yet it is often riddled with misinformation. Further, few guidelines exist for producing reliable, peer-reviewed content. This study describes a framework for creating and disseminating evidence-based videos on polycystic ovary syndrome (PCOS) and thyroid conditions to improve health literacy and tackle misinformation. The study aims to evaluate the creation, dissemination, and impact of evidence-based, peer-reviewed short videos on PCOS and thyroid disorders across social media. It also explores the experiences of content creators and assesses audience engagement. This mixed methods prospective study was conducted between December 2022 and May 2023 and comprised five phases: (1) script generation, (2) video creation, (3) cross-platform publication, (4) process evaluation, and (5) impact evaluation. The SIMBA-CoMICs (Simulation via Instant Messaging for Bedside Application-Combined Medical Information Cines) initiative provides a structured process where medical concepts are simplified and converted to visually engaging videos. The initiative recruited medical students interested in making visually appealing and scientifically accurate videos for social media. The students were then guided to create video scripts based on frequently searched PCOS- and thyroid-related topics. Once experts confirmed the accuracy of the scripts, the medical students produced the videos. The videos were checked by clinical experts and experts with lived experience to ensure clarity and engagement. The SIMBA-CoMICs team then guided the students in editing these videos to fit platform requirements before posting them on TikTok, Instagram, YouTube, and Twitter. Engagement metrics were tracked over 2 months. Content creators were interviewed, and thematic analysis was performed to explore their experiences. The 20 videos received 718 likes, 120 shares, and 54,686 views across all platforms, with TikTok (19,458 views) and Twitter (19,678 views) being the most popular. Engagement increased significantly, with follower growth ranging from 5% on Twitter to 89% on TikTok. Thematic analysis of interviews with 8 out of 38 participants revealed 4 key themes: views on social media, advice for using social media, reasons for participating, and reflections on the project. Content creators highlighted the advantages of social media, such as large outreach (12 references), convenience (10 references), and accessibility to opportunities (7 references). Participants appreciated the nonrestrictive participation criteria, convenience (8 references), and the ability to record from home using prewritten scripts (6 references). Further recommendations to improve the content creation experience included awareness of audience demographics (9 references), sharing content on multiple platforms (5 references), and collaborating with organizations (3 references). This study demonstrates the effectiveness of the SIMBA CoMICs initiative in training medical students to create accurate medical information on PCOS and thyroid disorders for social media dissemination. The model offers a scalable solution to combat misinformation and improve health literacy.

Thyroid Function in the Time of COVID-19: A Systematic Review of Disease Progression and Vaccination Effect

Objectives: This systematic review sought to address three key questions: (1) what differences in abnormal thyroid function test results are observed between COVID-19 patients and healthy individuals? (2) How does the severity of COVID-19 infection influence the development of thyroid dysfunction? (3) What impact do COVID-19 vaccines have on thyroid function and autoimmune processes? Methods: A literature search was conducted in PubMed, Web of Science, and Scopus from December 2019 to April 2023 to identify studies on thyroid dysfunction in COVID-19 patients without pre-existing thyroid conditions. The search focused on observational and case-control studies. Results: The literature search yielded 329 reports, from which duplicates and unrelated publications were excluded. Ultimately, 21 studies met the inclusion criteria and were selected for review. A second literature search yielded 605 reports, from which 5 studies were selected for inclusion in the systematic review. Conclusions: The findings suggest that SARS-CoV-2 infection can induce transient and reversible thyroid dysfunction, possibly through direct viral effects on the thyroid gland or via indirect immune-mediated mechanisms. Clinicians should be mindful of the potential, albeit rare, thyroid-related adverse effects of COVID-19 vaccines and monitor thyroid function, particularly in high-risk individuals.

Thyroid function status in patients with hypothyroidism on thyroxine replacement and associated factors: a retrospective cohort study in primary care

BackgroundLong-term management of patients with hypothyroidism on thyroxine replacement requires thyroid function test (TFT) monitoring once every six–12 months as recommended by clinical practice guidelines. This study determined their thyroid function status during two-year follow-up visits in primary care, and the factors influencing their thyroid status, and assessed the optimal interval for TFTs.MethodsA retrospective cohort study was conducted on adults with a clinical diagnosis code for hypothyroidism in their electronic health records taken from a group of polyclinics in Singapore between July 2017 and June 2020. The follow-up thyroid status was categorized as under-replacement (TSH ≥ 3.70mIU/L), over-replacement (TSH ≤ 0.65mIU/L) or euthyroid (TSH 0.65–3.70mIU/L). The patients’ demographic, clinical and TFT data were analyzed using appropriate statistical tests during the two-year follow-up. Stepwise logistic regression analysis identified the factors associated with suboptimal thyroid control. Kaplan–Meier analysis was used to compare their thyroid function status in association with the interval between TFT monitoring.ResultsData from 5,749 eligible subjects (mean age 62.1 ± 13.29 years; 79% female; 79.7% Chinese) were analyzed. After a two-year follow-up, 61.9% (n = 3558) of all subjects were euthyroid, with 29.5% (n = 1694) being under-replaced and 8.6% (n = 497) over-replaced. However, thyroid status did not differ significantly with the various dose regimen (daily, segmented, or alternate days) (p = 0.193). Stepwise logistic regression showed that thyroxine under-replacement was significantly associated with the male gender (AOR = 1.25,95%CI = 1.03–1.51,p = 0.02) and obesity (AOR = 1.34,95%CI = 1.08–1.66,p = 0.008). Every unit (μg/kg body weight) increase in the mean daily thyroxine dose was associated with 2.72 times greater odds of over-replacement. When comparing thyroid function monitoring at intervals of 13-24 months, monitoring at shorter intervals (≤ 12 months) was less likely to detect thyroxine under-replacement (AOR = 0.57,95%CI = 0.44–0.74,p < 0.001) and over-replacement (AOR = 0.62,95%CI = 0.41–0.97,p = 0.033). Among the 3,312 adults who were euthyroid at baseline, 22.2%, 41.7% and 59.6% had suboptimal thyroid control at 6, 12 and 24 months respectively (Kaplan–Meier analysis).ConclusionAround six in ten patients were euthyroid with thyroxine replacement for hypothyroidism in primary care over two years. Thyroxine under-replacement was associated with male gender and obesity. The proportion of euthyroid patients developing abnormal thyroid function doubled with TFTs at six, 12 and 24-month intervals.

Low Serum Fibroblast Growth Factor 21 Level and Its Altered Regulation by Thyroid Hormones in Patients with Hashimoto's Thyroiditis on Levothyroxine Substitution.

Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism exerting protection against atherosclerosis by multiple actions on the blood vessels, liver, and adipose tissues. We aimed to investigate serum FGF21 level and its relation to thyroid hormones and metabolic parameters among patients with Hashimoto's thyroiditis (HT). Eighty patients with HT on levothyroxine treatment and eighty-two age- and BMI-matched adults without thyroid disease serving as controls were enrolled. Serum FGF21 concentrations were determined with an enzyme-linked immunosorbent assay. Median serum FGF21 level was significantly lower in HT patients compared with controls (74.2 (33.4-148.3) pg/mL vs. 131.9 (44.8-236.3) pg/mL; p = 0.03). We found a positive correlation between FGF21 and age, triglyceride, total cholesterol, and low-density lipoprotein cholesterol in both groups, while thyroid stimulating hormone and C-reactive protein showed a positive correlation, and thyroxine had an inverse correlation with FGF21 only in control subjects. According to multiple regression analyses, thyroid status is the main predictor of FGF21 in healthy controls, while it is not a significant predictor of FGF21 among HT patients on levothyroxine supplementation therapy. Our results indicate that the physiological role of thyroid function in the regulation of FGF21 synthesis is impaired in HT patients, which may contribute to the metabolic alterations characteristic of HT patients.

Investigating thyroid function and iodine status in adolescents with and without paediatric major depressive disorder.

Depression has been associated with subclinical hypothyroidism and altered hypothalamic-pituitary-thyroid axis functioning. Adequate iodine nutrition is essential for healthy thyroid functioning. We therefore determined associations of iodine and thyroid status with paediatric major depressive disorder (pMDD) among Swiss adolescents and explored whether associations are sex-specific and mediated by stress. We conducted a matched case-control study in 95 adolescents with diagnosed pMDD and 95 healthy controls. We assessed depression severity using the Children's Depression Rating Scale-Revised and stress using the perceived stress scale (PSS) and measuring hair cortisol levels. We determined iodine status by measuring urinary iodine concentrations (UIC) and thyroid status by thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in serum. Median (IQR) UIC did not differ between cases (121 (87, 174) µg/l) and controls (114 (66, 183) μg/l, P = 0·3). Median TSH and FT4 were lower in cases than controls (TSH: 1·36 (0·91, 2·00) mlU/l v. 1·50 (1·18, 2·06) mlU/l, P = 0·039; FT4: 14·7 (12·9, 16·9) pmol/l v. 15·7 (14·3, 17·2) pmol/l, P = 0·004). The prevalence of hypothyroxinaemia (normal TSH; low FT4) was higher among female cases than controls (21 % v. 4%, P = 0·006). PSS scores were higher while hair cortisol was lower in cases than controls (PSS: 25 (20, 28) v. 11 (7, 15), P < 0·001; cortisol: 2·50 (1·34, 3·57) pg/mg v. 3·23 (1·79, 4·43) pg/mg, P = 0·044). After adjusting for confounders, the associations of TSH and hair cortisol with pMDD were no longer significant. Furthermore, TSH and FT4 were not associated with PSS scores and hair cortisol levels. Summarising, iodine nutrition was adequate for adolescents with and without pMDD. However, FT4 concentrations were lower in those with pMDD, and 1 in 5 female adolescents with pMDD were hypothyroxinaemic.

Patient satisfaction and operator proficiency in gasless transaxillary endoscopic thyroidectomy under IONM: a retrospective cohort study.

This study aims to evaluate the surgical safety and effectiveness of gasless transaxillary endoscopic thyroidectomy (GTET), assess patients' short-term perceptions and long-term outcomes, and delineate the learning curve and key surgical techniques of the operators. Clinicopathological and postoperative follow-up data from patients with unilateral thyroid cancer in the same period were collected. These patients were divided into the GTET group and the traditional open surgery group to compare and analyze the differences and explore the factors affecting the learning curve of GTET. Patients who chose GTET had better general health and thyroid conditions than those in the open group, and the quality of postoperative life was better in the GTET group than in the open group, with the main differences between the two groups being appearance and neck and shoulder function. The GTET learning curve in this study peaked at 19 cases, with slight differences between left and right, and a larger sample size is still needed to explore the factors affecting the learning curve. GTET has a reliable safety and efficacy profile for patients with unilateral thyroid cancer. Intraoperative nerve monitoring (IONM) techniques require some adaptation in GTET. In some respects, patients' postoperative experience and quality of life are superior to those of conventional open surgery. There is a learning curve for GTET, but large samples are still needed to explore its true significance.

8806 A Case of Autoimmune Thyroid Switching

Abstract Disclosure: J. Case: None. R.V. Chemitiganti: None. D. Suravajjala: None. Autoimmune thyroid disease comprises both hyper- and hypothyroid states including Graves' disease and Hashimoto's thyroiditis, respectively. The predominant antibody activity, demonstrable by thyrotropin receptor antibody, predicts the clinical presentation and treatment; thyrotropin receptor antibodies may act as a stimulatory or inhibitory stimulus upon the thyroid gland recognized as thyroid stimulating antibody(TSAb) and thyroid blocking antibody(TBAb). Rarely patients may transition from a hyperthyroid to a hypothyroid state and vice versa if the predominant antibody activity shifts which may occur due to a variety of mechanisms and characteristics related to each individual patient and treatment course. A 29 year old female presented to establish care for autoimmune thyroiditis. She was diagnosed with Graves' disease at age 19 when pregnant and treated with propylthiouracil; she switched to methimazole for the next six years when her thyroid function normalized and therapy discontinued. Two years later she became concerned with weight gain and her thyroid function was reevaluated demonstrating hypothyroidism and she was treated with levothyroxine 25mcg daily until presentation. Further labwork revealed undetectable TSI, and TPO antibody elevated at 177 u/mL. She became clinically and biochemically euthyroid on levothyroxine 50mcg daily. Switching between hyper- and hypothyroid states is a rare occurrence among patients with may attributable factors. Both antithyroid drugs including methimazole as well as replacement therapy with levothyroxine may alter the antibody milieu and so the predominant ratio and activity among TSAb and TBAb thereby leading to a shift in clinical presentation and thyroid state. Pregnancy may lead to hemodilution contributing to lessening of autoimmune activity which may return following delivery leading typically to a shift from TSAb to TBAb. Uncontrolled hyper- and hypothyroidism may affect dendritic activity leading to altered presentation and increased immune reactivity. The unlikely occurrence of switching from a hyperthyroid to a hypothyroid state based upon autoimmunity as in this patient was likely affected these factors. Recognition of this potential transition and associated factors would lead to beneficial monitoring and possibly development of assays more attuned to this phenomenon with better capability in maintaining a euthyroid state and potentially predicting a transition. Presentation: 6/3/2024

7308 A Case of Thyroid Hormone Resistance Associated With a Novel Mutation in the THRA Gene

Abstract Disclosure: J.A. Siddiqui: None. M. Barbosa: None. V. Fettig: None. C.J. Romero: None. Introduction: Thyroid hormone resistance (THR) is a syndrome leading to decreased response of target organs to thyroid hormone. Normal thyroid hormone action is mediated by thyroid hormone nuclear receptors and is essential for normal development and metabolism. Two isoforms are encoded by the thyroid hormone receptor α and β genes (THRA and THRB). Mutations in THRB are commonly reported with limited cases of THRA mutations. We report a 15-month-old and her mother with a pathogenic variant in the THRα receptor leading to thyroid hormone resistance. CASE: A 15-month-old ex-39-week gestation female was born small for gestational age (birth weight: 2450 grams,3rd %ile and birth length: 17 inches,1st %ile). The newborn screen was normal. She presented with macroglossia, low tone and global developmental delay. She had severe constipation complicated by rectal prolapse that required surgical correction. There are multiple relatives (mother, maternal half-brother and maternal grandparents) with neurodevelopmental issues. The mother’s previous genetic evaluation was non-diagnostic. Mother reports a thyroid condition but without treatment. The patient was initially referred to genetics and whole exome sequencing revealed a heterozygous c.1205 T&amp;gt;C p. (L402P) variant in the THRα gene, which was maternally inherited and reported as a variant of uncertain significance. On physical exam, Heart rate was 112 bpm; height &amp;lt;1%ile (Z-score -3.22 SD), weight 3%ile (Z-score -1.89 SD). Patient has a wide anterior fontanelle (4x3 cm), macroglossia and delayed teeth eruption. Other exam findings: non-palpable thyroid and postaxial polydactyly on the 5th digit of the right toe. Thyroid hormone testing: normal TSH 1.829 uIU/mL, low total T4 4.4 mcg/dL, low Free T4 of 0.58 ng/dL and high free T3 of 4.24 pg/mL. Levothyroxine treatment was initiated(25 mcg daily). After 1 month treatment, TSH level was 0.23 uIU/mL, total T4 was 6.1 mcg/dL and low reverse T3 of 5.8 ng/dL. DISCUSSION: Thyroid hormone resistance due to THRα mutations are rare and under-recognized. The main clinical phenotype includes growth retardation, delayed development, decreased muscle tone, delayed tooth eruption and constipation. Unlike patients with THRβ mutations, the hypothalamus-pituitary-thyroid axis in patients with THRα mutations is minimally affected with a normal TSH level. Total T3 levels are elevated with slightly low total T4 and free T4:T3 ratio is low. Treatment with levothyroxine leads to suppressions of TSH levels, therefore confirming intact central T3 feedback loop. Reports, however, show minor clinical improvements with treatment; therefore further research is needed in these patients to explore more effective therapeutic options. We present a case of a novel congenital THRA mutation leading to a clinical phenotype consistent with THR. She continues care in our clinic with hopes to further study her mutation. Presentation: 6/2/2024

8518 Prevalence of Hearing Dysfunction in Patients with Autoimmune Thyroid Disorders, Thyroid Eye Disease and the General US population: A Claims Database Analysis

Abstract Disclosure: T.J. Smith: Consulting Fee; Self; Amgen Inc, Viridian, Minghui, Lassen, Lundbeck. Other; Self; US patents covering the use of IGF-1 receptor inhibitors in TED which are held by UCLA and the Lundquist Institute. A. Meyers: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. Q. Fu: Stock Owner; Self; Amgen Inc. Other; Self; Amgen Inc, former employee. R.J. Holt: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. K. Zhu: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. Background: Autoimmune thyroid conditions including Graves’ disease (GD) have been associated with hearing impairment.([1]-3) Approximately 90% of patients (pts) with thyroid eye disease (TED) have hyperthyroidism/GD. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, significantly improves TED signs/symptoms and became the first FDA-approved treatment for TED in 2020. Hearing-related adverse events were identified in pivotal trials of teprotumumab in TED.4 This epidemiology study aims to describe the prevalence of hearing loss/ototoxicity via claims data in commercially insured pts with autoimmune thyroid conditions, TED, and those receiving teprotumumab, as well as the general population (gen pop). Methods: Five mutually exclusive cohorts were created using deidentified claims data (Merative MarketScan®): GD pts (index is first GD diagnosis [dx] code), TED pts (index is later of both GD dx or eye symptom codes within 1 yr), teprotumumab pts (index is first claim for teprotumumab), other Thyroid Disorders (TD) pts (index is TD dx), and gen pop pts. Pts with teprotumumab claim were excluded from other cohorts. Eligible pts were ≥18 years (yrs) of age, continuously enrolled for ≥6 months pre and post index, between 1/1/2020-12/21/2021. Demographics (age, sex) were described between the cohorts and the gen pop. Proportions of pts with inpatient and outpatient claims for hearing loss/ototoxicity claims and proportions with hearing loss/ototoxicity claims in the 3 yrs preceding index were calculated. Age-standardized prevalence was presented using gen pop as the reference. Results: Of 21,256,714 eligible pts, 82,629 GD, 4,455 TED, 2,758 teprotumumab, 1,261,250 TD and 4,857,408 gen pop pts were identified. 47% pts in the gen pop cohort were female vs 72.1-75.7% in the other cohorts. Gen pop cohort was younger (mean [SD] age: 53 [15.1] yrs) vs 58.0-61.5 [15.1-15.6] yrs in other cohorts. Age-standardized prevalence of hearing loss/ototoxicity claims on/after index date was 3.3% for GD, 5.2% for TED, 4.3% for teprotumumab, 3.9% for TD, and 3.9% for gen pop pts. Hearing loss/ototoxicity claims were prevalent in the 3 years prior to index among these patients: 30.8% GD, 36.6% TED, 35.4% teprotumumab, 31.5% TD, and 27.3%) gen pop pts had a hearing loss/ototoxicity claim. Conclusions: In this descriptive unadjusted analysis, we observed similar prevalence of hearing loss/ototoxicity claims across thyroid disorders, TED pts, teprotumumab pts, and the gen pop group. Between 27%-37% had claims prior to thyroid diagnosis or receiving teprotumumab. It is expected that future analyses could adjust the rates for potential confounders across cohorts.

7699 Unanticipated Harmony: PD-L1 Inhibitor Treatment for Urothelial Cancer Resolving Graves' Disease in a Patient - A Case of Immune Modulation Surprises

Abstract Disclosure: K. Tiwari: None. C.A. Resta: None. Introduction: Programmed death ligand 1(PD-L1) inhibitors constitute a class of immune checkpoint inhibitors (ICI) employed in treating various cancers. Thyroid-related immune-related adverse events (irAEs), such as hypothyroidism, are found to be in 3.9% of patients with PD L1 treatments. This case explores a unique scenario where a patient with pre-existing Graves' disease, undergoing PD-L1 inhibitor therapy for cancer, experienced an unexpected sequence of events leading to the default treatment of Graves' disease and subsequent progression to hypothyroidism. Case Presentation: A 59-year-old male, who had been effectively managed on methimazole for Graves' disease over two years and had chosen not to pursue definitive therapy for the condition, presented with tremors and a bilaterally enlarged thyroid gland during treatment for urothelial carcinoma. Laboratory findings included a TSH of 0.03 mIU/L (nl 0.40-4.50 mIU/L), fT4 of 3.4 ng/dL (nl 0.8-1.8 ng/dl), and tT3 of 284ng/dl (nl 76-181 ng/dl). The patient had recently started treatment with Avelumab, a PD-L1 inhibitor, as maintenance therapy following 4 cycles of gemcitabine/cisplatin cycles. Concerned about worsening Graves' disease, the methimazole dose was increased, and follow-up labs were performed after three weeks. These results showed low-normal fT4 of 0.8 ng/dL, TSH of 1.01 mIU/L(N), and low T3 of 58 ng/dL. TSI was mildly elevated at 168%. Due to rapidly changing thyroid function tests and suspicion of thyroiditis, methimazole was stopped. A PET scan a week later indicated diffuse thyroid uptake consistent with thyroiditis. Repeat labs 10 days later revealed a TSH of 67.36 mIU/L(H) and fT4 of 0.4 ng/dL(L), indicative of overt primary hypothyroidism. The patient exhibited symptoms including fatigue, constipation, and cold intolerance. The patient was initiated on levothyroxine therapy to address overt primary hypothyroidism, likely secondary to destructive thyroiditis from ICI. Discussion: Thyroid irAEs are typically incidentally discovered during routine monitoring of ICI treatment. It includes thyrotoxicosis, subclinical hypothyroidism, and overt hypothyroidism. These events commonly occur in patients lacking pre-existing thyroid conditions. In contrast, our patient, with a history of Graves' disease, experienced resolution of Graves' disease following treatment with PD-L1 inhibitor use with subsequent progression to hypothyroidism. Conclusion: This case emphasizes the importance of recognizing atypical presentations of thyroid irAEs in individuals with pre-existing thyroid disorders undergoing ICI treatment. Presentation: 6/3/2024

8640 Thyroid Orbitopathy in Pregnancy

Abstract Disclosure: Z. Maisonet -Feliciano: None. M. Alvarado: None. L.A. Gonzalez-Rodriguez: None. M. Ramirez: None. L. El Musa Penna: None. J. Segarra-Villafane: None. I.C. Arroyo: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. Thyroid orbitopathy, often associated with Graves' disease, is characterized by the inflammation and swelling of ocular tissues. Its occurrence or exacerbation during pregnancy is infrequent, primarily due to the immunosuppressive state inherent in pregnancy. In most instances, the immunosuppression associated with pregnancy leads to a reduction in TRAb levels, although they continue to be present in women who have an active form of the disease. The course and severity of ocular manifestation do not always correlate with thyroid hormone levels. Strict control of thyroid function is crucial in patients with thyroid eye disease. This report sheds light on the rare occurrence of thyroid orbitopathy during pregnancy, a condition that complicates treatment due to potential risks to both the mother and the child. In this case, a 35-year-old pregnant woman with no prior history of thyroid issues exhibited symptoms of hyperthyroidism in her first trimester, including unintended weight loss, anxiety, and tremors in the upper limbs. She also presented with ocular discomfort, diplopia, and eyelid lag. Thyroid tests confirmed Graves Disease, with a significant elevation in Thyroid Stimulating Immunoglobulin (TSI): 243 %, Free thyroxine (T4): 1.08 ng/dl and Triiodothyronine (T3): &amp;gt;1.89 units and decreased Thyroid Stimulation Hormone (TSH): 0.001 uIU/ml. Ophthalmic examination revealed mild Graves orbitopathy due to bilateral exophthalmos (measured by Hertel’s exophthalmometer) 21mm on both sides, Marginal reflex distance (MDR) 1: right eye 9 mm and left 7mm. MDR 2: right eye 6mm and left eye 7mm. Right upper eyelid retraction, lagophthalmos of the right eye, limitation in the upward movement of the left eye, and vertical diplopia on extreme gazes without signs of orbital compression. Considering her normal FT4 levels and the mild nature of her hyperthyroidism, the decision was made to prioritize the mother's treatment while minimizing fetal risk, thus opting not to initiate antithyroid medication but to closely monitor her thyroid function. Symptomatic management of her orbitopathy was provided including lubricating eye drops and an eye patch. Throughout the progression of her pregnancy, her TSI levels exhibited a decreasing trend while FT4 remained within normal limits. Following delivery, there was a notable improvement in her ocular symptoms, and her TSH started increasing up to normal values of 1.29 uIU/ml and FT4 remained in range. This report underscores the importance of recognizing uncommon presentations of autoimmune thyroid conditions, such as thyroid orbitopathy, during pregnancy. It emphasizes the complexities and necessary considerations in treating these cases. A collaborative approach involving endocrinology, ophthalmology, and obstetrics is essential to safeguard the health of both the mother and the fetus. Presentation: 6/1/2024

Foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations.

FOXE1 mutations in humans are associated with cleft palate and hypothyroidism. We previously developed a foxe1 mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we investigate the thyroid status and skeletal phenotype of adult foxe1 mutants. Mutant fish have increased expression of tshβ in the pituitary, and of hepatic dio1 and dio2. In plasma, we found higher Mg levels. Together these findings are indicative of hypothyroidism. We further observed mineralization defects in scales due to enhanced osteoclast activity as measured by increased expression levels of tracp, ctsk, and rankl. Gene-environment interactions in the etiology of FOXE1-related craniofacial abnormalities remain elusive, which prompts the need for models to investigate genotype-phenotype associations. We here investigated whether ethanol exposure increases the risk of developing craniofacial malformations in foxe1 mutant larvae that we compared to wild types. We found in ethanol-exposed mutants an increased incidence of developmental malformations and marked changes in gene expression patterns of cartilage markers (sox9a), apoptotic markers (casp3b), retinoic acid metabolism (cyp26c1), and tissue hypoxia markers (hifaa, hifab). Taken together, this study shows that the foxe1 mutant zebrafish recapitulates phenotypes associated with FOXE1 mutations in human patients and a clear foxe1-ethanol interaction.

Diffuse Enlargement of the Thyroid Gland as a Result of the Impact of Adverse Factors on the Pituitary-thyroid Cystem of Children

The problem of diffuse goiter has attracted the attention of many researchers in recent years. The main reason for the formation of endemic goiter is iodine deficiency in the environment. Epidemiological studies conducted in recent years have shown that almost all regions of Kazakhstan are regions of endemic goiter with natural iodine deficiency. Some of them are characterized by an increase in the severity of endemic goiter. The reasons contributing to the progression of goiter endemicity are the cessation of iodine prophylaxis, the deterioration of the environmental situation and the social situation of a significant part of the population. The purpose of this work was to study the features of thyroid status in children with diffuse goiter. Material and methods There were 38 children under our supervision, 20 (main group) had diffuse (endemic) goiter (5 boys and 15 girls), 18 children (control group) - 5 boys and 13 girls, children in the control group were considered healthy. Results As a result of comparing indicators of the functional state of the pituitary-thyroid system in patients with diffuse goiter, a relatively increased level of thyroid-stimulating hormone is noted, which indicates the negative impact of diffuse goiter on the thyroid status of children. Conclusions As a result of the manifestation of diffuse goiter in children, metabolic disorders of the pituitary-thyroid system occur. Signs of thyroid deficiency are most often observed in children living in iodine-deficient areas. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1213-1218

Interpretation of TSH results can be improved by reference values fluctuating in time.

The secretion of thyroid stimulating hormone (thyrotropin, TSH), is characterized by a marked circadian rhythm. Plasma or serum TSH values are significantly lower in the afternoon and in the evening as compared to the early morning. As in clinical practice, blood sampling time shows an important variation, a reliable assessment of thyroid status is often not an easy task for the clinician. The biological variation of TSH plays a major role in the intra-individual variability of TSH results in serum or plasma. The observed intra-day variation largely exceeds the reported inter-vendor variation and the coefficient of variation of clinical TSH assays. Therefore, a mathematical solution was sought for correcting interpretation of TSH results for sampling time. We have developed a cosinor model which allows to compensate TSH decision values for the fluctuating serum or plasma TSH concentrations throughout the day. The following mathematical function could be derived: corrected TSH cutoff_value (mIU/L)=0.40+0.24*cos(((π/12) *T)+6) in which T represents the time (hours). This mathematical function can be easily implemented into a laboratory's informatics system and furthermore allows a better tailored diagnosis of (subclinical) hyperthyroidism, regardless the blood sampling time. Implementing the corrected cut-off values result in a marked reduction of apparent (false positive) hyperthyroidism diagnosis, in particular in the afternoon.

Prevalence of thyroid dysfunction among pregnant women in the horn of Africa: A systematic review and Meta-analysis

BackgroundThyroid dysfunction ranks among the most prevalent endocrine disorders. This disorder during pregnancy has been linked to adverse effects on both the mother and the baby. However, there is a scarcity of data and inconsistent documentation regarding thyroid issues in pregnant women in low-income nations. ObjectiveThe aim of this systematic review and meta-analysis was to determine the general prevalence of thyroid disorders in pregnant women. MethodsTo identify relevant studies, a comprehensive search was conducted across Scopus, PubMed, Science Direct databases, and Google Scholar and repository registers from January 1, 2000 to December 31, 2023. Ten pertinent publications were chosen for the final meta-analysis. Relevant data was extracted using Microsoft Excel and analyzed using STATA software version 17, employing a random-effect model. Sensitivity analysis was conducted to evaluate each study's impact on the outcome, and Egger's test was utilized to detect publication bias. A trim-and-fill analysis was executed to adjust for bias in the effect estimate. Heterogeneity across studies was assessed using Cochran's Q statistic and I2 statistics. Subgroup analysis was carried by study design, country and publication year. ResultsIn this systematic review and meta-analysis, the prevalence of thyroid dysfunction among 2538 pregnant women was 12.0 % (95 % CI: 8.00 %–17.00 %). To account for the significant heterogeneity observed, a random effect model was utilized. Specifically, the prevalence of hypothyroidism in pregnant women was determined to be 10.00 % (95 % CI: 4.00–16.00 %) with a high level of heterogeneity (I2 = 94.27 %, p < 0.001). Notably, the sensitivity analysis conducted did not reveal any substantial impact on the overall pooled prevalence of thyroid dysfunction. ConclusionThe meta-analysis revealed a significantly higher rate of thyroid disorders among pregnant women compared to global estimates. To assess the effects of treating thyroid conditions on pregnancy outcomes and inform clinical decisions, it is recommended to implement cost-effective thyroid-stimulating hormone screening during pregnancy.

TO STUDY THYROID DYSFUNCTION IN PATIENTS WITH METABOLIC SYNDROME

Background: Metabolic syndrome (MetS) is a cluster of risk factors associated with increased cardiovascular disease and diabetes risk. Thyroid dysfunction (TD), especially hypothyroidism, has been observed more frequently in individuals with MetS. However, the relationship between thyroid function and metabolic syndrome components remains debated. This study aimed to explore the prevalence of thyroid dysfunction and its association with metabolic syndrome components in patients. Methods: A cross-sectional study was conducted at Sri Aurobindo Medical College &amp; P.G. Institute, Indore. A total of 120 patients meeting the International Diabetes Federation (IDF) criteria for metabolic syndrome were included. Detailed history, anthropometric measurements, blood pressure recordings, fasting blood sugar, lipid profile, and thyroid assays were performed. Statistical analysis using SPSS22 and Excel was employed to assess thyroid dysfunction prevalence and its correlation with metabolic syndrome components. Results: Among 120 patients with metabolic syndrome, 28% had thyroid dysfunction. Hypothyroidism was predominant, with subclinical hypothyroidism being the most common type. Females and older individuals (&gt;45 years) showed a higher prevalence of thyroid dysfunction. Patients with thyroid dysfunction exhibited altered metabolic syndrome components, including increased waist circumference, decreased HDL-C, elevated blood pressure, fasting glucose, and triglyceride levels. Conclusion: The study highlights a high prevalence of thyroid dysfunction, especially hypothyroidism, among patients with metabolic syndrome. These findings suggest a potential association between thyroid status and metabolic syndrome components. Screening for thyroid dysfunction in individuals with metabolic syndrome could aid in optimizing clinical management strategies. Further research with larger sample sizes and prospective designs is warranted to explore the impact of thyroid dysfunction management on metabolic syndrome outcomes.

Navigating the thyroid-gynecologic interplay: a systematic review and meta-analysis thyroid-gynecologic interaction.

Thyroid disorders are considered to be linked to various health issues, including gynecologic cancers. Studying this association is crucial in clinical practice. This approach was applied through searches in Scopus, WOS, PubMed, and Google Scholar. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed. The quality assessment was checked. The meta-analyses were performed using R-4.3.2 (COMPANY, CITY, STATE, COUNTRY) and SPSS version 28 (COMPANY, CITY, STATE, COUNTRY). The results demonstrated that 19 studies investigated the association between thyroid disorders and gynecologic cancers in adult females. The studies were categorized into two groups: group 1 examined thyroid status in various gynecologic cancers, while group 2 comprised case-control studies examining gynecologic cancer incidence in females with thyroid disorders compared to control. Among females with gynecologic cancers, 13% (95% confidence interval [CI], 10-17%) had hypothyroidism. When comparing hypothyroidism and hyperthyroidism across studies, the overall percentage for hypothyroidism was 14% (95% CI, 9-22%), while for hyperthyroidism, it was 3% (95% CI, 2-5%). The odds ratio for hypothyroidism in females with uterine cancer was 2.65 (P<0.05). Additionally, hypothyroidism showed a significant risk ratio of 1.3 (P<0.05) for different gynecologic cancers. However, hyperthyroidism was significantly associated with increased ovarian cancer mortality (RR, 2.14; P=0.03); conversely, hypothyroidism showed no significant relationship (RR, 1.35; P=0.26). The findings concluded that hypothyroidism is significantly associated with various gynecologic cancers, suggesting a potential role in its pathogenesis. Conversely, hyperthyroidism is linked to an increased risk of ovarian cancer mortality. Further research is needed to clarify whether hyperthyroidism predisposes females to ovarian cancer.

Neonatal Hyperthyroidism: Case Report and Literature Review

The onset of Graves' disease during pregnancy exposes the newborn to the risk of neonatal hyperthyroidism due to the transplacental passage of anti-thyroid-stimulating hormone (TSH) receptor antibodies. We report the case of a child whose mother was diagnosed with Graves' disease during pregnancy. Clinical hyperthyroidism appeared only a few days after birth and was confirmed by hormonal tests. Thanks to treatment with synthetic antithyroid drugs, the child's clinical and biological course was favorable. It is essential to systematically screen for neonatal hyperthyroidism in newborns of mothers with Graves' disease, as the absence of immediate clinical signs after birth does not rule out the diagnosis. The pediatrician must be aware of this thyroid condition even in the absence of an identified maternal history, in order to enable rapid therapeutic management.