Elevated Thyroid-stimulating Hormone Research Articles

The level of thyroid stimulating hormones in different gender and age and the association with the risk of coronary heart disease in cohort population

Objective: To analyze the thyroid stimulating hormone (TSH) levels in different genders and ages, and the association between TSH level and the risk of coronary heart disease. Methods: The baseline survey was conducted using a multi-stage cluster random sampling method from September to December 2015, in Jurong City, Jiangsu Province. A total of 10 703 participants were included in the analysis. The proportion of participants with abnormally elevated TSH defined by three cut-off values (4.5, 7.0, and 10.0 mU/L) were calculated. The cohort was followed up until August 2023 to collect and verify new cases of coronary heart disease. The population was divided into age-and gender-specific quintile subgroups based on TSH. Multivariate Cox regression analysis was used to examine the relationship between TSH and the risk of coronary heart disease. Results: The median age was [M (Q1, Q3)] 61.1(51.8, 67.9) years-old, and there were 4 168 males (38.94%) in the study. The proportions of participants with abnormally increased TSH rose with aging in different genders, and was higher in females than in males (all Ptrend0.05). A total of 206 participants with coronary heart disease at baseline were excluded, and the other 10 497 were followed up for an average of (7.33±1.49) years, during which 350 new cases of coronary heart disease occurred, and the cumulative incidence rate was 3.34%. The cumulative incidence rates among TSH quintile Q1-Q5 groups were 3.62%, 3.32%, 3.56%, 3.28% and 2.57% respectively. Multivariate Cox regression analysis indicated that compared with TSH Q1 group, participants in Q5 group had a lowest risk of coronary heart disease (HR=0.704, 95%CI: 0.498-0.994). The TSH Q5 group was associated with a reduced risk of coronary heart disease in individuals60 years old (HR=0.484, 95%CI: 0.243-0.965), and the risk of coronary heart disease decreased as TSH levels increased (Ptrend=0.008). Conclusions: TSH level increases with aging, and is higher in females than in males. In individuals 60 years old, higher levels of TSH may assaciate with a lower incidence rate of coronary heart disease.

Elevated thyroid-stimulating hormone levels, independent of Hashimoto's thyroiditis, increase thyroid cancer risk: Insights from genetic and clinical evidence.

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disorder and thyroid cancer (TC) is the most prevalent endocrine malignancy. Recent debates have focused on whether HT increases the risk of developing TC. This study combined Mendelian randomization (MR) and observational methods to investigate the potential causal relationship between HT and TC risk. First, we performed two-sample MR and multivariable MR (MVMR) analysis using the genome-wide association studies (GWAS) data from multiple databases, including European and East Asian populations, to estimate the effect of HT and thyroid-stimulating hormone (TSH) levels on TC risk. Second, we conducted an observational study using data from the National Health and Nutrition Examination Survey (NHANES) database and evaluated the association between HT, TSH, and TC prevalence through logistic regression model and restricted cubic spline model. Our MR findings revealed no significant association between HT and TC risk in both populations. However, elevated TSH levels significantly increased TC and papillary thyroid carcinoma (PTC) risk, while lower TSH levels were associated with reduced TC risk. Further MVMR analysis and an observational study confirmed this. Additionally, our observational study also indicated no significant relationship between HT and TC prevalence and abnormal TSH levels correlated with higher TC risk. HT was not a TC risk factor, but high TSH levels increased TC risk. Controlling TSH within normal ranges through thyroid hormone replacement was recommended to reduce TC risk in HT patients with elevated TSH levels, even those without symptoms.

Diagnostic Utility of Cord Thyroid-Stimulating Hormone (TSH) in Congenital Hypothyroidism and Its Association With Perinatal Factors: A Study From a Tertiary Referral Centre in Hyderabad, India.

Introduction Congenital hypothyroidism (CH) is one of the most common, easily treatable, causes of long-term neurodevelopmental complications in children. The prevalence of CH in India is much higher compared to other countries. Although developed countries have well-established neonatal screening programs, a uniform nationwide screening program at birth is still not established in India. Cord blood thyroid-stimulating hormone (TSH) screening is crucial in diagnosing congenital hypothyroidism even with advancements in expanded newborn screening programs. The aim of this study was to determine the prevalenceof elevated cord blood TSH levels and factors associated with it among newborns and to analyze the false positive rates ofelevated cord blood TSH levels among the study population and factors associated with it. Methods This retrospective cross-sectional studywas conducted among 51,251 live newborn babies born at Fernandez Hospital, Hyderabad, India, over a period of five years from January 2019 to December 2023.The data of all the mothers and newborns was retrieved from medical records and details of maternal age, parity, co-morbidities, mode of delivery, gestational age of the newborn at delivery, gender, number of babies, APGAR score, and birth weight were obtained. As per hospital policy, 5 ml of cord blood sampleof all newborn babies was collected from the umbilical cord at the time of birth. Samples were analysed for cord TSH batchwise by the enzyme-linked immunosorbent assay (ELISA) method. As per the manufacturer, the normal biological reference intervals are <20 uIU/mL. All the cord TSH values > 20 uIU/ mL were considered abnormaland advised a repeat serum TSH test within 14 days of life. Cord TSH values that were higher than the biological reference range after retesting were considered positive for CH. All the initial and repeat results were retrieved from the neonatal digital database. Results Out of 51,251 live newborn babies, 71 (0.14%) were confirmed with a diagnosis of congenital hypothyroidism.The prevalenceof CH in our study population was 1.4 per 1000 live births. Anaemia was found to be a statistically significant predictor of true positive cases (p<0.05).In our study, while evaluating risk factors for elevated cord TSH levels, we found that the babies born by vaginal delivery had higher cord TSH levels than babies born by lower segment caesarean section (LSCS) (p<0.001). The other variables considered in the study which include maternal age, BMI, parity of mother, gender of the baby, birth weight, gestation age and APGAR score were not statistically significant for CH. Conclusion The prevalence of congenital hypothyroidism was 1.4 in 1000 in our study. Mode of delivery and maternal anaemia had an impact on elevated cord TSH levels. These factors should be considered while interpreting cord TSH values.Cord TSH testing is an effective screening tool for CH.It helps in the early detection of thyroid dysfunction in newborns, enabling timely intervention and treatment to prevent developmental delays and other complications. This study presents evidence supporting the inclusion of cord blood TSH as a predictive factor in CH screening programs.

CONGENITAL HYPOTHYROIDISM IN NEWBORN AND ASSOCIATION WITH SOCIODEMOGRAPHIC PARAMETERS AMONG NEONATE DELIVERED AT MILITARY HOSPITAL IN A CITY OF CENTRAL INDIA

Objectives: The present study aims to assess the incidence of congenital hypothyroidism (CH) among neonates in a tertiary care hospital in central India, examining its association with various sociodemographic parameters. Methods: This cross-sectional study, conducted between January and December 2022, included all live births at a tertiary care center in Jabalpur, Madhya Pradesh. Cord blood thyroid-stimulating hormone (TSH) levels were measured for all newborns as part of routine screening. Sociodemographic data, including maternal age, gestational age, birth order, and newborn sex, were collected. Universal sampling was employed, encompassing all consenting parents and their neonates. Results: Among 388 live births, TSH values ranged from 0.23 to 35.59 mIU/L, with a mean TSH of 8.76±5.92 mIU/L. Of the neonates, 95.9% had normal TSH levels, while 4.1% exhibited elevated levels. Subsequent follow-up identified CH in two neonates (5.2 per thousand live births). Analysis revealed no significant association between elevated TSH levels and maternal age or newborn sex. However, a significant association was observed with gestational age. Birth order also displayed significance, with the third birth order having a higher proportion of neonates with raised TSH levels. Conclusion: This study highlights the importance of CH screening in preventing long-term complications and the various sociodemographic factors linked to CH, such as maternal age, gestational age, and birth order.

Obesity-related subclinical hypothyroidism in childhood: Elevated triglycerides but not basal metabolicrate.

Studies on the associations between obesity-related subclinical hypothyroidism with basal metabolic rate and risk factors of cardiovascular disease in children and adolescents are scarce. Retrospective cohort study of children with obesity (n = 294) from the Uppsala Longitudinal Study of Childhood Obesity cohort. Differences in basal metabolic rate quantified by indirect calorimetry, and the cardiovascular risk factors; body mass index, blood lipids, fasting and 2 h oral glucose tolerance test glucose, glycated haemoglobin and insulin resistance, between subjects with and without subclinical hypothyroidism were investigated. The associations of baseline thyroid stimulating hormone (TSH) and ΔTSH with change in cardiovascular risk factors over time were assessed. Subjects with subclinical hypothyroidism had elevated triacylglycerides but no alterations in basal metabolic rate or other measured cardiovascular risk factors. ΔTSH was positively associated with Δtriacylglycerides, Δtotal-cholesterol and ΔLDL-cholesterol, independently of age, sex, Δbody mass index and ΔT4. In the subclinical hypothyroidism group, 92% of individuals normalised their TSH 0.9-2.9 years later. Children with obesity and subclinical hypothyroidism did not have an altered basal metabolic rate but elevated triacylglycerides. During the follow-up period, TSH changed in parallel with several blood lipids. Elevated TSH often normalised without pharmaceutical intervention within 3 years. The present study found that subclinical hypothyroidism in paediatric obesity is related to elevated triglycerides. The present study found that subclinical hypothyroidism is not associated to basal metabolic rate in paediatric obesity. TSH change over time correlated with the change in triglycerides and LDL and total cholesterol. Among subjects with subclinical hypothyroidism at baseline 92% normalised without pharmaceutical intervention within 3 years. This research adds to the knowledge of the longitudinal, natural course of elevated TSH in paediatric obesity which is expected to help to make informed decisions regarding follow-up and evaluation of this patient group.

Valifenalate-induced non-adverse thyroid changes via adaptive induction of uridine 5′-diphospho-glucuronosyltransferase (UGT) in the liver of dogs and rats but not humans

Some rat and dog toxicology studies with the fungicide valifenalate showed minimal, non-adverse thyroid changes, mostly above the maximum tolerated dose, and concomitantly with liver effects. This publication describes their mode of action (MOA), combining in vivo and new approach methodologies (NAMs), in a weight of evidence approach.Data demonstrate a MOA of liver enzyme induction via nuclear receptor CAR/PXR activation, increased thyroxine (T4) metabolism and elevated thyroid stimulating hormone (TSH) level, leading to thyroid follicular cell hypertrophy and increased thyroid weight. Non-human relevance of the MOA was demonstrated in in vitro cross species assays in rat, dog and human hepatocytes. Increased gene expression and activity of cytochrome P450s (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) were observed in rat and dog hepatocytes exposed to valifenalate, with increased T4 clearance and/or T4 glucuronidation/T4-UGT activity. Therefore, a causal relationship between increased liver enzyme induction and thyroid effects in dogs and rats is concluded. Rat hepatocytes were most sensitive, while valifenalate did not increase T4-UGT activity above 2-fold of vehicle control or T4 glucuronidation and T4 clearance in human hepatocytes. Consequently, valifenalate exposure in humans is unlikely to lead to decreased T4 levels, and subsequent thyroid and developmental neurotoxicity effects. Alternative human-relevant thyroid MOAs were excluded, i.e. inhibition of deiodinases (DIO), thyroperoxidase (TPO) or the sodium iodide symporter (NIS).Due to known species differences in thyroid homeostasis between humans and laboratory animals and, importantly, based on the presented data, this liver enzyme mediated MOA is considered not relevant for human hazard assessment.

Evaluation of Thyroid Activity in Patients with Liver Cirrhosis

Abstract Background: Liver cirrhosis is increasingly becoming a public health problem. The aim of study is to evaluate the relationship levels thyroid stimulating hormone (TSH), triiodothyronine (T3), free thyroxine (fT4) and and liver cirrhosis(LC) severity, measured by Child-Pugh (CP) and MELD scores. Methods: 419 patients diagnosed with liver cirrhosis were included in the study. Biological tests for TSH, T3, fT4 on admission and discharge were used. All analysis was performed using, One-Sample Wilcoxon test and Kruskal-Wallis test. Results: The mean values for TSH were statistically significant higher compared to normal values only at admission (p&lt;.05), and the mean values for T3 were statistically significant lower both on admission (p&lt;.001) and on discharge (p&lt;.001). No effect was observed for fT4. TSH on the admission and discharge moments were statistically significant differences (p&lt;.001), T3 (p&lt;.001) and fT4 (p&lt;.004). The CP also influenced the hormone's values for TSH at admission (p&lt;.01 and discharge (p&lt;.001), and T3 at admission (p&lt;.001) and discharge (p&lt;.001) but not for fT4. For MELD score, a low power positive associations were observed only with TSH, on admission and discharge and negative associations with F3, in both situations. Conclusions: Elevated TSH levels at admission, coupled with their negative correlation with the CP score and differences between TSH-CP group C and groups A and B, highlighting the necessity for vigilant endocrine monitoring in hepatic patients. Also, admission T3 levels are lower than normal and negatively correlate with cirrhosis severity and MELD scores underscore potential clinical utility of monitoring thyroid function in assessing disease progression and improving patient survival outcomes.

Hyperthyroidism, hypothyroidism, thyroid stimulating hormone, and dementia risk: results from the NHANES 2011-2012 and Mendelian randomization analysis.

As the world ages, dementia places a heavy burden on society and the economy, but current methods of diagnosing dementia are still limited and there are no better therapies that target the causes of dementia. The purpose of this work is to explore the relationship between thyroid disease, thyroid stimulating hormone (TSH) concentrations, free tetraiodothyronine (FT4) concentrations and cognitive function. This study utilized cognitive function and thyroid data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) to assess the relationship between different groups of TSH and FT4 concentrations and cognitive function using weighted logistic regression and restricted cubic spline (RCS), and then used two-sample Mendelian Randomization (MR) to assess the causal relationship between hyperthyroidism, hypothyroidism, TSH and FT4 concentrations with dementia. Our analysis of the 2011-2012 NHANES data showed that the individuals with low TSH concentrations had higher Alzheimer's Disease Word List Registry Consortium1 (CERAD1) and CERAD.delay.recall scores than individuals with high TSH concentrations, and individuals with low FT4 concentrations had higher CERAD3 and Animal Fluency Test scores than individuals with high FT4 concentrations. Our results also showed a non-linear relationship between serum TSH and FT4 concentrations and the Animal Fluency Test. The TSH concentrations within the range of 1.703 to 3.145 mIU/L exhibit a positive correlation with Animal Fluency Test, whereas concentrations outside this range are negatively correlated with Animal Fluency Test. The FT4 concentrations exhibited a positive correlation with Animal Fluency Test to the left of the FT4 concentrations inflection point (0.849 ng/L), whereas to the right of this inflection point, correlation was negative. MR analysis results further indicate that genetic predisposition to hyperthyroidism may be associated with a reduced risk of dementia and vascular dementia(VaD). Conversely, genetic predisposition to hypothyroidism appears to be linked with an increased risk of dementia and VaD. Additionally, genetic predisposition to elevated TSH concentrations may be correlated with a heightened risk of risk of Alzheimer's disease (AD). This study provides evidence of a nonlinear relationship between TSH and FT4 concentrations and cognitive function, with hyperthyroidism decreasing the risk of dementia and VaD, hypothyroidism increasing the risk of dementia and VaD, and elevated serum TSH concentrations increasing the risk of AD. Furthermore, prioritizing early detection, diagnosis, and treatment through the assessment of thyroid function in individuals at high risk for developing dementia is of paramount importance. This strategy has the potential to significantly contribute to the prevention and deceleration of dementia progression.

Identification and determination of the urinary metabolite of iodotyrosine invivo

BackgroundCongenital hypothyroidism screening traditionally relies on detecting elevated thyroid-stimulating hormone levels, yet this approach may not detect a specific type of congenital hypothyroidism caused by iodotyrosine dehalogenase-1 (Dehal1) deficiency. The deficiency of this enzyme prevents the deiodination of mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) in the process of iodine recycling. This underscores the potential use of iodotyrosine or its metabolites as non-invasive urinary biomarkers for early diagnosis of congenital hypothyroidism. However, the urinary metabolites of MIT/DIT have not yet been discovered. Thus, this study aimed to identify the urinary metabolites of iodotyrosine in experimental models. MethodGas chromatography mass spectrometry was used to identify the urinary metabolites of iodotyrosine following intraperitoneal injection of MIT in rats. An isotope dilution mass spectrometric assay was developed for assessment of identified metabolites. Urine samples from Dehal1 knockout mice were used to confirm the results. ResultsWe identified novel iodotyrosine metabolites, 3-iodo-4-hydroxyphenylacetic acid (IHPA), and 3,5-diiodo-4-hydroxyphenylacetic acid (Di-IHPA) as the primary urinary metabolites of MIT and DIT respectively. The concentrations of urinary IHPA and Di-IHPA were significantly higher in Dehal1 knockout mice. ConclusionOur findings suggest that IHPA is detected in larger quantities and may hold more clinical significance than previously identified biomarkers like MIT and DIT, making it a promising candidate for diagnosing congenital hypothyroidism or other conditions associated with iodine recycling inhibition.

Approach to Newborns with Elevated TSH: A Different Perspective from the International Guidelines for Iodine-Deficient Countries.

Lowering of thyroid-stimulating hormone (TSH) cutoffs in newborn screening programs has created a management dilemma by leading to more frequent detection of neonates with elevated TSH concentrations due to false-positive results, transient neonatal hyperthyrotropinemia (NHT), and milder forms of congenital hypothyroidism. Current consensus guidelines recommend starting treatment if the venous TSH level is >20 mU/l in the face of a normal free thyroxin (FT4) level, which is an arbitrary threshold for treatment decisions. In countries such as Türkiye, where transient NHT may be more common due to iodine deficiency and/or overload, putting this recommendation into daily practice may lead to unnecessary and over treatments, long-term follow-ups, and increased workload and costs. In this review, we addressed alternative approaches for infants with elevated TSH concentrations detected at newborn screening. Our management approach can be summarized as follows: Infants with mild NHT (TSH<20 mU/l) should be followed without treatment. In moderate NHT (TSH 20-30 mU/l), treatment or monitoring decisions can be made according to age, TSH trend and absolute FT4 level. Moderate cases of NHT should be treated if age at confirmatory testing is >21 days or if there is no downward trend in TSH and FT4 level is in the lower half of age-specific reference range in the first 21 days. In in-between cases of moderate NHT, thyroid ultrasound can guide treatment decision by determining mild cases of thyroid dysgenesis that require life-long treatment. Otherwise, monitoring is a reasonable option. Infants with compensated hypothyroidism (TSH>30 mU/l) and persistent hyperthyrotropinemia (>6-10 mU/l after neonatal period) should receive L-thyroxine treatment. But all treated cases of isolated TSH elevation should be closely monitored to avoid overtreatment, and re-evaluated by a trial off therapy. This alternative approach will largely eliminate unnecessary treatment of infants with transient NHT, mostly caused by iodine deficiency or excess, and will reduce workload and costs by preventing unwarranted investigation and long-term follow-up.

6983 Pembrolizimab Induced Hypophysitis: Uncommon Side Effect Leading To Late Diagnosis

Abstract Disclosure: T. Chaudhary: None. O. Syed: None. A. Shridar: None. R. Kaur: None. O. Chaudhary: None. M.S. Zubair: None. Background: Pembrolizumab, an immune checkpoint inhibitor, has shown efficacy inducing remission in various malignancies. Associated immune-related adverse effects (irAEs) have been recorded but cases of concomitant hypophysitis and thyroiditis are rare. Clinical case: The patient is a 41-year-old male with a past medical history significant for metastatic melanoma of the left calf, status post sentinel lymph node biopsy and left inguinal lymph node dissection, treated with pembrolizumab for one year. He initially presented with a severe headache that was preceded by two months of fatigue and impaired concentration. CT and MRI head were both unremarkable while lab work was significant for cortisol 0.2 ug/dL and adrenocorticotropic hormone (ACTH) 1.1 pmol/L. A full hormone panel was ordered which showed normal insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Free testosterone was at the lower end of normal. Prolactin was elevated at 27.3 ng/mL. The thyroid function tests showed primary hypothyroidism with elevated thyroid stimulating hormone (TSH) at 109 uIU/mL, low T4 at 1.5 ug/dL, and low free T4 at 0.4 ng/dL. There were no signs or symptoms of posterior pituitary dysfunction. The patient was diagnosed with hypophysitis and started on hydrocortisone 20 mg once daily along with levothyroxine 175 mcg once daily. DEXA scan showed normal bone mineral density. Subsequently, the patient presented to our care and reported symptom improvement after taking the prescribed medication however he continued to develop fatigue by the end of the day. Therefore, hydrocortisone prescription was switched to 15 mg in the morning and 10 mg at noon. A repeat thyroid function panel, sex hormone binding globulin, and LH were ordered, to be followed up at the patient's next visit. The patient was also advised to wear a medical alert bracelet at all times moving forward. Conclusion: Due to non-specific symptoms at onset, hypophysitis can be undiagnosed or misdiagnosed therefore it is important to have a high clinical suspicion with patients on PD-1 inhibitors presenting with such symptoms. It is also imperative to order a full set of hormones as this patient had concomitant primary hypothyroidism. Presentation: 6/1/2024

8208 Unexpected And Significant Rise In TSH In The Setting Of Relugolix Use

Abstract Disclosure: A.Y. Groysman: None. A. Poloju: None. P. Majety: None. T. Abraham: None. Background: Relugolix is a gonadotropin-releasing hormone antagonist used as androgen deprivation therapy for metastatic and nonmetastatic castration-resistant prostate cancer that was FDA-approved in December 2020. Common side effects include hot flashes, increased glucose and triglycerides, and decreased hemoglobin. We report a case of Relugolix interference with the absorption of levothyroxine, which has not been reported in the literature. Case: A 79-year-old white man with high-risk, Gleason 9 prostate cancer and Hashimoto’s hypothyroidism presented for evaluation of elevated thyroid stimulating hormone (TSH) level- 52.87 mIU/L (0.28-4.10 mIU/L). He did not have cold intolerance, constipation, fatigue, or weight gain. He was diagnosed with hypothyroidism in 1998 and was on a stable dose of levothyroxine 88mcg daily from 2016 until the time of this presentation. He is adherent and reports following a routine of having breakfast with coffee soon after taking levothyroxine for many years. In June 2022, his TSH was 4.48 mIU/L. In July 2022, he started taking Relugolix along with levothyroxine. Following this, his TSH levels increased to 30.08 mIU/L (FT4: 0.67 ng/dL), 35.43 mIU/L (FT4: 0.57 ng/dL), 52.87 mIU/L (FT4: 0.48 ng/dL) on 2/24/23, 3/3/23, and 3/14/23, respectively. No new medications were reported. His other medications were atorvastatin, tamsulosin, and vitamin D, which he took at night. He did not take calcium or biotin supplements. He had gradual weight gain (8 lbs) over the last 9 months. Levothyroxine dose was increased from 88 to 125 mcg daily and he was instructed to separate Relugolix from levothyroxine so he started taking Relugolix at bedtime. Repeat TSH was low at 0.12 mIU/L. The levothyroxine dose was eventually titrated back to 88 mcg daily and TSH was 5.2 (appropriate for age). Conclusion: Several medications are known to interfere with the absorption of levothyroxine. Our case suggests that Relugolix may be one of them. The significant rise in TSH and levothyroxine requirements months after starting Relugolix and the ability to return to the previous dose of levothyroxine only by separating Relugolix from levothyroxine strongly suggests that there is an interference between these medications that has not been reported. Presentation: 6/2/2024

7915 A Case of Severe Hypothyroidism in a Patient with Nephrotic Syndrome presenting with Rhabdomyolysis requiring Levothyroxine and Liothyronine combination therapy

Abstract Disclosure: S.S. Mohammed: None. E.T. Ngo: None. S. Tadisina: None. B.M. Drees: None. Background: Nephrotic syndrome is known to worsen hypothyroidism via urinary loss of thyroid binding globulin, transthyretin, albumin and other proteins, often requiring escalating levothyroxine doses. Severe uncontrolled hypothyroidism can result in rhabdomyolysis, although this presentation is quite rare. Clinical case: We present a case of a 50-year-old male with long-standing Hashimoto’s hypothyroidism, biopsy-proven minimal change disease with nephrotic syndrome, dyslipidemia, and hypertension, who was admitted for generalized myalgia, weakness, and progressive swelling of bilateral hands and feet for one month. He had been off levothyroxine 3 months prior to presentation. He previously required large doses of oral levothyroxine, as high as 350mcg daily, but never achieved a euthyroid state despite reported adherence to therapy with the high levothyroxine doses.Laboratory workup showed severe hypothyroidism (free thyroxine &amp;lt;0.25ng/dL [0.6-1.6ng/dL] with markedly elevated thyroid stimulating hormone 282.03 mIU/mL [0.3-5.6mIU/mL]), along with acute kidney injury and rhabdomyolysis (Creatine kinase 4882 U/L[38-234U/L]). He was hemodynamically stable with intact mentation and was not deemed to be in myxedema coma. Physical examination was consistent with hypothyroidism with periorbital swelling, dry skin, deep hoarse voice, bilateral hand and feet edema, and delayed deep tendon reflexes. Thyroid function tests and clinical symptoms failed to improve after 8 days, despite high doses of levothyroxine IV (200mcg). Creatine kinase remained high at 4994 U/L [38-234U/L] despite adequate fluid hydration. Liothyronine 5mcg orally was started in addition to levothyroxine 200mcg IV. Repeat thyroid function tests after 2 days of combined IV levothyroxine and oral liothyronine therapy showed significant downtrend in TSH to 154.12 uIU/ml [0.3-5.6mIU/mL] and increase in free thyroxine to 0.44ng/dl [0.6-1.6ng/dL]. Creatine kinase also down trended to 3181U/L[38-234U/L] on D4 of IV levothyroxine 200mcg IV with liothyronine 5mcg daily. He was discharged stable and clinically improved on oral levothyroxine and liothyronine. Laboratory evaluation 10 days later showed further improvement in TFTs (TSH 66.0[0.3-5.6mIU/mL]), free thyroxine 0.6 [0.6-1.6ng/dL] Conclusion: This case presents a unique and unusual clinical course in symptomatic primary hypothyroidism with rhabdomyolysis and AKI. Rhabdomyolysis due to hypothyroidism, without an obvious precipitating factor, has been previously reported, but is very rare. There is limited evidence regarding combination treatment with levothyroxine and liothyronine in primary hypothyroidism; however, as demonstrated in this patient, combination therapy resulted in clinical and biochemical improvement of thyroid function. Presentation: 6/2/2024

8141 A Rare Case of Follicular Adenoma with Osseous Metaplasia and Mature Bone Formation- Is Surveillance Important?

Abstract Disclosure: K. Madani: None. Y. Al-Khazraji: None. D.H. Sacoto: None. G.K. Rai: None. R. Belokovskaya: None. A.A. Franco-Akel, MD: None. Osseous metaplasia and mature bone formation (MBF) are common in malignant thyroid and parathyroid tumors. It is very unusual to have MBF in a benign tumor-like follicular adenoma, as in the case we describe. We found only twelve such cases reported in the literature, and none addressed the cancer risk or need for surveillance for the development of potential malignancy. Thus, further studies are required to investigate the need for surveillance in patients not undergoing excision and in those with remnant thyroid tissue post-removal of the adenoma for recurrence. A 43-year-old female with history of hyperlipidemia and hypothyroidism had an incidental finding of midline neck mass during the evaluation of a left upper extremity lipoma. Ultrasound of the neck showed two nodules in the Left (L) thyroid lobe: a complex nodule measured 2.2 x 1.2 x 2.1 cm and a calcified nodule measuring 1.5 x 0.8 x 0.6 cm. MRI of the neck revealed a 1.9 cm heterogeneously enhancing nodule in the mid to lower pole of the L thyroid lobe. The patient had symptoms suggestive of compression, such as dysphagia, odynophagia, and hoarseness; thus, left hemothyroidectomy was performed. Tissue biopsy was notable for follicular adenoma with osseous metaplasia and mature bone formation. The patient remained clinically and biochemically euthyroid, with only mildly elevated thyrotropin level, and treatment with levothyroxine 25 mcg once daily was initiated. On post-surgical follow-up, there was a lack of data to support close monitoring modality and strategy for the remnant thyroid lobe and neck nodal compartments. We concluded with the patient to follow up in a clinical visit for a physical exam of the neck and to obtain a follow-up sonogram at an interval of six months, in addition to monitoring TSH levels to guide hypothyroidism therapy. Osseous metaplasia has not been established as a premalignant condition, but in certain tissues like the esophagus, metaplasia is a risk factor for malignant conversion, for instance, in Barrett’s esophagus leading to esophageal adenocarcinoma. Moreover, MBF in thyroid tissue has been attributed to the activity of basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2), which are linked with mitogenesis and tumorigenesis. Thus, the question arises if post-excision surveillance is required in patients with a history of osseous metaplasia in remnant thyroid tissue post-lobectomy or partial thyroidectomy. At this point, more epidemiological data on similar cases may help us understand the true risk of this clinical scenario, in order to develop a reasonable approach for surveillance. Presentation: 6/3/2024

Thyroid dysfunction prevalence in high-risk pregnant women and maternal and neonatal consequences after delivery: A retrospective cohort study

Objective: To evaluate thyroid dysfunction prevalence and its consequences in high-risk pregnant women and their children. Methods: In this retrospective cohort study, data from high-risk pregnant women who were referred to a governmental referral hospital in Qom, Iran from March to August 2022 were collected. The thyroid disorders were determined according to the 2017 American Thyroid Association guidelines. The predictors of a mother’s hypothyroidism and its fetal and maternal consequences were assessed. Independent t-test, Chi-square test, and logistic regression were used for bivariate and multivariate analysis. Results: 293 women were included. The prevalence of hypothyroidism and hyperthyroidism based on the thyroid stimulating hormone classification was 32.5% and 2.0%. The prevalence of subclinical and overt hypothyroidism was 6.1% and 4.1%, and the prevalence of subclinical and overt hyperthyroidism was 2.4% and 1.4%, respectively. Family history of thyroid disorders was the most important predictor of hypothyroidism during pregnancy (OR=2.6, 95% Cl=1.0-6.6, P=0.002), while preterm delivery (OR=2.2, 95% CI=1.3-6.8, P=0.220) and elevated neonate thyroid stimulating hormone (OR=1.2, 95% CI=1.1-1.3, P=0.041) were the most important consequence of hypothyroidism. Conclusions: Hypothyroidism is a highly prevalent thyroid disorder in high-risk pregnant women. Thyroid function screening should be performed in all pregnant women to increase the detection of subclinical and overt hypothyroidism during pregnancy.

Clinical values of preoperative red blood cell distribution width and platelet parameters in patients with papillary thyroid carcinoma.

The prevalence of thyroid carcinoma is increasing, and papillary thyroid carcinoma (PTC) is the most frequent subtype. More and more attention is being concentrated on the association between inflammation indicators and malignant tumors. The aim of the present study was to analyze whether the preoperative red blood cell distribution width (RDW) and platelet parameters, including mean platelet volume (MPV) and platelet distribution width (PDW), can be applied to distinguish between patients with PTC or papillary thyroid microcarcinoma (PTMC) and healthy controls, and to explore the associations with clinicopathological characteristics. The study retrospectively compared the RDW, MPV and PDW values of 780 patients with PTC or PTMC against a healthy control group. Receiver operating characteristic (ROC) curves were conducted to determine diagnostic accuracy. Furthermore, the clinicopathological features of the patients with PTC or PTMC were compared between higher and lower platelet parameter groups based on the RDW, MPV and PDW values. Significantly higher preoperative RDW, MPV and PDW values were found in patients with PTC or PTMC compared with those of the healthy group. ROC curve analysis showed that the area under the curve (AUC) plus 95% confidence interval (95% CI) values of RDW, MPV and PDW were 0.808 (0.780-0.835), 0.771 (0.743-0.799) and 0.711 (0.681-0.742), respectively. When RDW and MPV were combined together, the AUC (95% CI) value was enhanced to 0.858 (0.835-0.881) for the patients with PTC. For the patients with PTMC, RDW, MPV and PDW had AUC (95% CI) values of 0.812 (0.783-0.840), 0.779 (0.749-0.808) and 0.718 (0.685-0.751), respectively. When RDW and MPV were combined together, the AUC (95% CI) value was enhanced to 0.858 (0.835-0.881). A higher RDW was significantly associated with being female, deeper tumor infiltration, and normal FT3 and FT4 levels. A higher PDW was significantly associated with elevated thyrotropin receptor antibody levels. In conclusion, as convenient and available inflammation indicators, RDW, PDW and MPV have diagnostic ability and can distinguish between patients with PTC or PTMC and healthy controls. In addition, the combined application of RDW and MPV can improve the diagnostic power. The values of RDW and MPV were associated with clinicopathological characteristics. To the best of our knowledge, this is the first study to prove the usefulness of preoperative RDW combined with MPV in diagnosing patients with PTC or PTMC.

Thyroxine Replacement Therapy during Ramadan Fasting: A Narrative Review

Abstract Introduction Ramadan fasting-induced changes in eating and sleeping patterns pose a risk of influencing thyroid hormone levels. There is a recognition of the potential impact of fasting and feasting on levothyroxine (L-T4) absorption. Materials and Methods A narrative, nonsystematic literature review from two major medical online databases (PubMed and Google Scholar) from their inception to the search day (February 22, 2024). A relevant combined search term was used. The retrieved literature is narrated in a concise account. Results There is a relationship between metabolism and thyroid-stimulating hormone (TSH). This relationship contributes to transient metabolic disturbances that influence the pharmacodynamics and pharmacokinetics of various drugs, adding complexity to the management of hypothyroidism during Ramadan fasting. Several observational studies have studied the changes in thyroid function levels during unmodified L-T4 regimens. Experimental trials explored the impact on body weight, well-being, and thyroid functions when the timing of L-T4 administration changes. Findings are far from homogeneous due to different study protocols. A recent meta-analysis demonstrated a significant post-Ramadan increase in TSH levels among euthyroid patients. L-T4 timing points, encompassing pre-Iftar, post-Iftar, and pre-Suhoor, are associated with elevated TSH levels after Ramadan fasting. The emphasis on individualized L-T4 regimens during Ramadan fasting is underscored, with recommendations for patients to refrain from food for at least 3 hours before and 30 minutes after L-T4 intake to ensure optimal compliance by most experts. The association between adherence to L-T4 during Ramadan fasting and maintaining euthyroid status is highlighted, encouraging patients to follow prescribed regimens diligently. Modified dosing frequencies, such as weekly regimens, exhibit promising results, especially in patients grappling with compliance issues. Proactive consultations with physicians before Ramadan are needed to review the latest thyroid function test and make possible dose adjustments. Conclusion Managing hypothyroidism during Ramadan necessitates an understanding of medication timing, food-drug interactions, and prior regimens. Adherence, facilitated by flexibility, plays a critical role in achieving euthyroid status.

Associative Learning in Subclinical Hypothyroidism at Different Ranges of Thyroid Stimulating Hormone: A Cambridge Neuropsychological Test Automated Battery (CANTAB) Study of Visual Paired Association Learning Task.

Associative learning deficits are constantly found in subclinical hypothyroidism (SCH). Despite achieving normal thyroid stimulating hormone (TSH) levels, a considerable number of patients undergoing levothyroxine (LT-4) treatment frequently complain about memory retrieval. The Paired Association Learning (PAL) task involves computerised testing on the CANTAB- Cambridge Neuropsychological Test Automated Battery, also considered a screening tool for Alzheimer's disease (AD). This study aimed to investigate the impact of different levels of TSH on visual associative learning in SCH and determine if these impairments were reversed with LT-4. A total of 134 participants were included in this cross-sectional study. Group 1: 35 healthy controls; patients with SCH (Group 2: 33 newly identified cases; Group 3: 32 patients on LT-4 with elevated TSH; Group 4: 34 euthyroid but on LT-4). A thyroid profile and a neuropsychological clinical assessment were done. The visual PAL task was performed on CANTAB. PAL was significantly impaired (p = <0.05) in all 3 patient groups as compared to Group 1. The PAL total errors (adjusted) scores were significantly higher in Groups 2 and 3, indicating that associative learning is definitely impaired in SCH, reaching levels previously seen in patients with AD. Our findings encourage screening for visual associative learning or memory retrieval in patients with SCH. The study present has established a more reasonable threshold of TSH 2.5mIU/L to encourage examination of associative learning and the initiation of LT-4 in SCH. Poor PAL task performance in patients with SCH may have significant implications in clinical settings for suspecting AD.

Pathological correlation between eosinophils and thyroid nodules based on medical image testing

Thyroid nodule is a common thyroid disease, but the study of its pathology and pathogenesis is still limited. As a non-invasive diagnostic method, medical image examination is of great value to study the pathological correlation of thyroid nodules. The purpose of this study was to investigate the expression of eosinophils in medical image examination and the pathological correlation between eosinophils and thyroid nodules. The study analyzed the pathological reports of a group of patients with thyroid nodules examined by medical images and performed corresponding imaging scans or examinations. The imaging data is processed, including image reconstruction, data transmission and other steps, to generate images that can be diagnosed by doctors. Thyroid function and parameters of leukocyte were collected and compared.The serum levels of TT4 and fT4 were observed lower in G2 group, while thyroid stimulating hormone (TSH) was higher compared to G1 group before surgery. Compared to G2 group, eosinophils count and percentage were lower in G1group (p < 0.05) post-surgery and lower ratio of eosinophils count with lymphocyte count (ELR) were observed in G1 group patients (p < 0.05).Elevated TSH is closely related to malignant TN per surgery, while lower ELR suggesting that TN removed thoroughly. Relevant cut-off values required further study to guide the diagnosis, treatment and follow-up of TN.

Causal role of thyroid function in functional outcome after ischemic stroke: A Mendelian randomization study

BackgroundPrevious observational studies have suggested that thyroid function may be associated with functional outcome after ischemic stroke (IS). Nevertheless, the causal relationship remains unclear. This study aimed to explore the causal effect of thyroid function [thyroid-stimulating hormone (TSH), free thyroxine (FT4), hyperthyroidism, and hypothyroidism] on functional outcome (based on the modified Rankin scale) after IS by two-sample Mendelian randomization (MR) analysis. MethodsInverse variance weighted (IVW) was the primary method for evaluating causal associations. In addition, six additional MR methods (MR-Egger regression, weighted median, maximum likelihood, simple mode, weighted mode, and MR-PRESSO) were employed to supplement IVW. Furthermore, various sensitivity tests were conducted to assess the reliability: (i) Cochrane's Q test for assessing heterogeneity; (ii) MR-Egger intercept test and MR-PRESSO global test for evaluating horizontal pleiotropy; (iii) leave-one-out sensitivity test for determining stability. ResultsThe results of IVW indicated that elevated TSH levels significantly improved functional outcome after IS (OR = 0.74, 95 % CI: 0.57-0.97, P = 0.028). In addition, six additional MR methods suggested parallel results. However, no causal effect of FT4, hyperthyroidism, and hypothyroidism on functional outcome after IS was identified. In addition, sensitivity tests demonstrated the reliability of the MR analyses, suggesting that the MR analysis was not influenced by significant heterogeneity and horizontal pleiotropy. ConclusionsOur MR study supported that elevated TSH levels might improve functional outcome after IS. Therefore, regular monitoring and maintenance of stable TSH levels may benefit patients recovering from IS.