Elevated TSH Levels Research Articles

Association of pre-op TSH levels with Thyroid Carcinoma in a Tertiary Care Setup in Karachi, Pakistan

Objectives: This study aimed to explore the relationship between pre-operative TSH levels and the presence of thyroid cancer in patients with nodular thyroid disease in the Pakistani population, using data gathered from patients treated at Dr. Ruth K. M. Pfau Civil Hospital Karachi. Study Design & Setting: A cross-sectional study was conducted at the Dow University of Health Sciences and Dr. Ruth K. M. Pfau Civil Hospital Karachi from January 2022 to December 2022. Methodology: Patients with thyroid swellings (presenting with either solitary nodules or with multinodular goiter), both benign as well as suspected/confirmed malignancy based on FNAC results were recruited in the study. Preoperative TSH levels, along with other clinical data, were collected. Thyroidectomy was carried out in patients fulfilling the criteria for surgery, with specimens sent for histopathology. An independent t-test was used to compare TSH levels between malignant and benign nodules. Results: A total of 82 patients were enrolled. Malignancy was confirmed in 41.5% (25 papillary carcinoma, 9 follicular carcinoma). Significantly higher mean TSH levels were observed in patients with malignant nodules (4.76 IU/mL) compared to those with benign nodules (2.48 IU/mL) (p < 0.001). Conclusion: This study suggests a potential association between elevated pre-operative TSH levels and thyroid cancer in the Pakistani population. These findings warrant further investigation to explore causality and potential underlying mechanisms. The study highlights the value of TSH monitoring, particularly in resource-constrained settings.

7165 A Case of Severe Myxedema Coma with Levothyroxine Allergy

Abstract Disclosure: A. Rothstein Costris: None. A. Yaseen: None. S. Levy: None. Introduction: Myxedema coma is a life threatening condition with a mortality rate of 25-60%. Untreated, it can lead to fatal physiological changes. The treatment is thyroid hormone replacement therapy, alongside supportive care for complications. Clinical Case: A 65-year-old woman, who has been dealing with untreated hypothyroidism since 2012 and reported allergies to various levothyroxine brands, presented with falls, weakness, and exacerbated leg numbness. During the examination, she exhibited periorbital edema, non-pitting edema in the lower extremities, bradycardia, and hypothermia. The blood work revealed an elevation in TSH levels at 301 uIU/L (0.45-5.33 uIU/mL). The patient was administered IV Synthroid (200 mcg), Atropine, and Hydrocortisone due to concerns about myxedema coma. After four hours, the patient experienced angioedema and hypotension, necessitating intubation. This situation was complicated by a pulseless electrical activity (PEA) arrest. Following cardiopulmonary resuscitation and the administration of epinephrine, the patient achieved return of spontaneous circulation. The allergy team assessed the patient for potential anaphylactic shock from IV Synthroid. Subsequently, the patient was initiated onIV Liothyronine and Hydrocortisone, leading to improvement in mental status over a period of a few weeks, and no adverse effects were reported. Thyroid labs improved to TSH of 53 (0.45-5.33 uIU/mL), FT3 of 3.3 (2.5-4.4 pg/mL) and total T3 of 133 (87-178 ng/dl). Upon discharge, the patient was prescribed Liothyronine, with plans to perform a Levothyroxine desensitization test in the outpatient setting. Conclusion: Myxedema coma is an endocrine emergency. Patients usually present with deteriorating mental status, hypothermia, and multiple organ system abnormalities. The diagnosis relies more on the clinical presentation and physical examination than on laboratory results. Thyroid replacement therapy serves as the cornerstone of treatment, with a preference for T4 due to its greater availability and lower likelihood of adverse events compared to Liothyronine, which may increase the risk of mortality at higher doses. Despite associated risks, incorporating low doses of Liothyronine is still considered in treatment plans, driven by concerns about reduced T4 to T3 conversion in myxedema patients. Hypersensitivity reactions to Levothyroxine are uncommon but may manifest as widespread hives, swelling, eczema-like skin rashes, elevated body temperature, and compromised liver function, with only one case reporting an anaphylactic reaction to Levothyroxine. In summary, the potential for experiencing an anaphylactic reaction to Levothyroxine exists, highlighting the need to contemplate alternative treatments, such as Liothyronine. Desensitization methods can be considered once the patient's condition is stable. Presentation: 6/2/2024

8500 Fvb/Ant Mice Carrying the Thr92Ala-Dio2 Polymorphism Have a Goiter

Abstract Disclosure: A. Batistuzzo: None. B. Bocco: None. E. McAninch: None. M.O. Ribeiro: None. A.C. Bianco: Consulting Fee; Self; Abbvie. Fvb/Ant Mice Carrying the Thr92Ala-Dio2 Polymorphism Have a Goiter Introduction: The Thr92Ala-DIO2 polymorphism is prevalent worldwide, with about 50% of the population carrying at least one polymorphic allele. Ala-D2 is ectopically located in the Golgi apparatus and causes endoplasmic reticulum (ER) stress. It is also about 40 % less active than Thr92-D2, thus T3 production could be compromised in carriers of the polymorphism. Objective: C57BL/6J (B6) mice carrying the Ala92-DIO2 polymorphism exhibit no significant thyroid phenotype as compared to control Thr92-Dio2 mice. Here we wished to test whether changing the genetic background of mice can influence the thyroidal impact of the Thr92Ala-DIO2 polymorphism. Therefore, we backcrossed B6-Thr92Ala-Dio2 mice to the FVB/Ant background for 8 generations. Methods: Mice were killed by asphyxiation in a CO2 chamber and blood collected from 7-18 weeks old female and male FVB/Ant Ala-Dio2 mice to measure plasma levels of TSH, T4, T3, and rT3. The thyroid gland was dissected, weighed and processed for histological analysis. The weight of the thyroid gland was normalized by femoral length. The QuPath Software was used for measuring follicular area, cell height, and the number of internalized follicular cells. Thr92-Dio2 mice of the same age and sex were used as controls. Data were analyzed using PRISM software and expressed as mean±SE (TH plasma levels and thyroid weight) or mean±SD (thyroid histology). A Student t-test was used to compare 2 groups. Results: Male and female Ala mice had significantly higher levels of TSH (males: 0.36±0.04 vs 1.1±0.21 ng/ml; p<0.01 and females: 0.017±0.006 vs 0.12±0.06 ng/ml; p<0.01), lower levels of plasmatic T4 (males: 2.9±0.2 vs 1.3±0.25 µg/dl; p<0.01 and females: 2.1±0.16 vs 1.15±0.16 µg/dl; p<0.001) and lower levels of rT3 (males: 23.8±2 vs 14.2±1.3 ng/dl; p<0.001 and females: 16.45±1.4 vs 10.4±1.17 ng/dl; p<0.01). Additionally, the thyroid gland of female polymorphic mice was heavier (4.3±0.39 vs 1.8±0.17 mg/cm; p<0.001) and both sexes presented enlarged thyroid follicle area (males: 1464±1464 vs 2055±2443 µm2; p<0.0001 and females: 1519±1364 vs 2597±2624 µm2; p<0.0001) and a higher number of internalized follicular cells (females: 0.06±0.007 vs 0.17±0.008 internalized cells/follicle; p<0.0001). No differences in the follicular cell height were observed. Discussion: In contrast to B6, FVB mice carrying the Thr92Ala-D2 polymorphism exhibit goiter, increased follicular area, slightly reduced serum T4 levels, and elevated serum TSH levels. These findings suggest that the impact of the Thr92Ala polymorphism varies according to the genetic background. They may explain why clinical studies of patients carrying the Thr92Ala-DIO2 polymorphism have yielded inconsistent results when different populations are analyzed. Presentation: 6/3/2024

8278 Myxedema Coma With COVID-19 Infection

Abstract Disclosure: R. Kalas: None. V. Manohar: None. N.S. Bapat: None. Y. Kim: None. Myxedema coma is a rare medical emergency that occurs in severe hypothyroidism with a mortality rate reaching 60%. The hallmarks include depressed mental status and hypothermia, but hypotension, hyponatremia, bradycardia, and hypoventilation can also occur. This complication can occur in patients with a longstanding history of severe hypothyroidism especially when precipitated by an acute event such as infection, myocardial infarction, or surgery. Prompt recognition and treatment of the condition is important to prevent fatal outcomes. We present a case of myxedema coma in the setting of COVID-19 infection and nonadherence to medication. A 91-year-old woman with history of hypothyroidism, hypertension, coronary artery disease, cardiomyopathy, and chronic obstructive pulmonary disease presented with dyspnea. Her home medications included levothyroxine 75 mcg daily, which she reported not taking for at least 3 weeks. Vital signs revealed a normal heart rate and blood pressure of 84 beats/min and 137/78 mmHg, but the patient was hypothermic to 35.7 °C. On exam, she was somnolent. Labs were notable for markedly elevated TSH level of 111 (0.380 - 4.700 uIU/mL), low free T4 level of 0.57 (0.93 - 1.70 ng/dL), random cortisol level of 25.5 (6.2-18.4 ug/dL), and positive SARS-COV-2 PCR test. Chest x-ray revealed bilateral lower lung parenchymal consolidations and arterial blood gas revealed a pH of 7.29 and pCO2 of 52.5 (35-45 mm Hg), indicating hypercapnia. She was treated for COVID pneumonia and given concern for COVID induced myxedema coma she was given IV levothyroxine 100 mcg for 2 days, after which the patient’s hypothermia and somnolence improved, with an improved repeat free T4 level 0.87 ng/dL. She was subsequently transitioned to oral levothyroxine 112 mcg daily and discharged after improvement of her COVID symptoms. Myxedema coma is a rare complication of decompensated hypothyroidism, frequently triggered by an infection. Thyroid hormone plays an important role in regulating both the innate and adaptive immune systems. As a result, individuals with hypothyroidism are at increased risk of acquiring infections, which can further lead to myxedema coma. COVID-19 infection has been associated with thyrotoxicosis, thyroiditis and hypothyroidism. Given the associated high mortality rate, regardless of the underlying precipitant, prompt diagnosis and early administration of thyroid hormone replacement therapy is crucial to improve outcomes. Presentation: 6/3/2024

8227 Complex Case of Myxedema Coma Complicated by Cardiac Arrest in a Geriatric Patient with Multiple Comorbidities

Abstract Disclosure: M. Parvez: None. L. Makahleh: None. S. Nagpal: None. A. Kavarthapu: None. V. Vedantam: None. Introduction: This case report details a rare instance of cardiac arrest in a patient with myxedema coma, a severe form of hypothyroidism. It highlights the diagnostic and therapeutic challenges in managing such complex endocrine emergencies. Case Presentation: A 70-year-old female with a history of hypothyroidism, type 2 diabetes, atrial fibrillation, pacemaker implantation, and COPD presented with a 3 day history of progressive lethargy and weakness. EMS found her with critically low blood glucose level of 20. History and Examination revealed non-compliance with thyroid medication and myxedematous features including moon-like facies, periorbital edema, generalized edema, elevated JVP, and cold extremities with sluggish capillary refill. In the ER, she was hypotensive, labs showed a significantly elevated TSH level of 30.55 (0.45-4.5), free T3 level of 1.2 (2.3-4.2), free T4 level of 1.12 (0.93-1.70), high lactate, metabolic acidosis, renal impairment, and liver enzyme elevation. These findings, coupled with the clinical presentation, led to the diagnosis of myxedema coma. The patient's critical state was further complicated by distributive shock, shock liver and oliguric AKI. Management included sodium bicarbonate infusion for severe acidosis, IV hydrocortisone, IV levothyroxine, and broad-spectrum antibiotics. Amiodarone was discontinued due to its potential contribution to acute liver injury and hypothyroidism. Despite interventions, she developed acute respiratory failure, requiring intubation and norepinephrine for low mean arterial pressure. Her renal function improved with pressor support, and her lactic acidosis resolved. She recovered quickly and was subsequently extubated. After stabilization, she was switched to oral levothyroxine and discharged. Shortly after discharge, she returned again with generalized weakness, confusion, and dysuria. ER evaluation revealed lethargy, hypotension, hypoglycemia, severe metabolic acidosis, and a UTI. She tested positive for Influenza. While in the ER, she had cardiac arrest, presenting with agonal breathing and PEA. CPR was initiated, achieving ROSC after two rounds and one dose of epinephrine. She was treated again with IV levothyroxine, and IV antibiotics. She recovered well and was discharged to rehab facility with re-education on compliance. Conclusion: This case exemplifies the complexity and challenges in managing a geriatric patient with multiple comorbidities, particularly in the context of myxedema coma. The intricate interplay of endocrine, cardiovascular, respiratory, and infectious complications necessitated a multifaceted and dynamic therapeutic approach. This case underscores the importance of compliance, vigilant monitoring, prompt recognition of complicating factors, and the need for a coordinated multidisciplinary approach in managing similar cases. Presentation: 6/2/2024

12361 An Unusual Case of Myxedema Coma

Abstract Disclosure: N. Hasan: None. D. Yang: None. T. Othman: None. J. Dai-Ju: None. Background: Most cases of Myxedema Coma are associated with primary hypothyroidism with significantly elevated TSH levels. However the presence severe illness can contribute to decreased TSH release even in the absence of central lesions. Case: 60 year old female was found down covered in feces. She was hypothermic to 89°F, with a pulse of 62. Physical exam revealed hair loss, thick tongue, non-pitting edema, and delayed relaxation of brachial reflexes. Labs showed Sodium of 123, blood glucose of 80. Thyroid function testing revealed only a mildy elevated TSH of 13 with free T4 <0.025. Anti-TPO antibodies were elevated at 157. MRI of the Sella was negative any lesions. Thyroid ultrasound showed atrophic bilateral thyroid lobes. Assessment for hypopituitarism did not show any significant deficiencies with Cortisol 45, ACTH 11, LH 0.5, FSH 8.5, IGF-33, and Total Testosterone 10. She was found to have septic shock secondary to perforated sigmoid colon requiring colectomy. She was initially loaded with Dexamethasone 4mg followed by IV Levothyroxine 100mcg, with steroids being discontinued after AI was ruled out. After treating her sepsis she was transitioned to 150mcg of oral Synthroid with improvement of her thyroid function tests to TSH of 2.7 and free T4 of 1.56. Discussion: The majority of Myxedema Coma is associated with primary hypothyroidism. In these cases, TSH levels are markedly elevated, often greater than 100. When the TSH is not as elevated as we would expect, many factors must be considered, the greatest being central hypothyroidism where TSH secretion may be impaired from pituitary tumors, surgery, radiation, and other causes. Our patient however did not have any central lesions on imaging and was found to have anti TPO antibodies with atrophic thyroid lobes on ultrasound suggestive of primary hypothyroidism. This brings us to the effect of acute illness on the balance of thyroid hormones. Conditions such as sepsis stimulates elevations in inflammatory cytokines which disrupt the physiologic response to release TSH. Previous studies involving sepsis revealed the main cytokines implicated are TNF alpha, Interferon gamma, IL-1, and IL-6. The degree of inadequate TSH secretion is often times proportional to the severity of illness and improves after recovery from the illness. Conclusion: Our body's response to critical illness involves complex hormonal changes which affect the HPA axis and can decrease TSH secretion, even in myxedema coma without central lesions. Presentation: 6/1/2024

Comorbid Hypothyroidism and Low-Alanine Aminotransferase-Associated Sarcopenia Associated with Shortened Survival: A Retrospective Study of 16,827 Patients over a 21-Year Period

Background: Hypothyroidism is very common worldwide. It is known to be associated with frailty which, in turn, is associated with increased morbidity and mortality in the elderly. Low ALT blood activity is an established marker for sarcopenia and frailty. The incidence and outcomes of the association between low ALT values and hypothyroidism, as manifested in elevated blood TSH levels, is unknown. The objective of this study was to assess if low ALT values could improve the prediction of clinical outcome in hypothyroid patients. Methods: This was a retrospective analysis of hospitalized patients in a large, tertiary hospital. Results: Over a period of 21 years, an overall population of 16,827 patients were identified as eligible to participate in this study. Within the study population, 726 (4.3%) were classified as suffering from hypothyroidism (TSH values > 6 MIU/L) and 2184 (13%) were classified as patients with sarcopenia (ALT < 12 IU/L). Within our patient population, hypothyroidism was associated with sarcopenia in a statistically significant manner (p = 0.011). Patients classified as suffering from both hypothyroidism and sarcopenia had significantly shorter survival: A multivariate analysis showed that the frail and hypothyroid group of patients had a statistically significant risk of mortality in the next 5 years (HR = 3.6; CI 2.75–4.71; p < 0.001). Conclusions: Sarcopenia and frailty are common comorbidities, bearing negative long-term clinical outcomes. Low ALT values could serve as a useful biomarker for screening of patients already diagnosed with hypothyroidism.

Assessment of Thyroid Profile in Patients with Hepatitis C Virus Infection

Background: Hepatitis C virus (HCV) infection remains a major public health concern in Pakistan, with potential impacts on thyroid function. Long-term HCV infection has been associated with thyroid dysfunction, but the extent of this relationship is not fully understood.Objective: This study aimed to evaluate the thyroid hormone profile in HCV-positive patients to assess the prevalence of thyroid dysfunction in this population.Methods: A cross-sectional study was conducted on 120 HCV-positive patients aged 18-70 years. Patients with liver cirrhosis, known thyroid disorders, or medications affecting thyroid function were excluded. Blood samples were collected, and thyroid hormones (TSH, FT3, FT4) were measured using an automated immunoassay system. Data were analyzed using SPSS version 25.0, with a p-value <0.05 considered statistically significant.Results: The study found that 17.50% of patients had elevated TSH levels, while 11.66% and 10.83% had elevated FT3 and FT4 levels, respectively. The mean values for TSH, FT3, and FT4 were 1.15 ± 0.515 µIU/mL, 1.10 ± 0.351 pg/mL, and 1.12 ± 0.361 ng/dL.Conclusion: The study demonstrated a significant association between HCV infection and thyroid dysfunction, highlighting the need for regular thyroid function monitoring in HCV-positive patients.

P-610 Elevated/high-normal TSH on day of beta-hCG in sub-clinical hypothyroid patients on levothyroxine associated with better odds of pregnancy in IVF cycles: a nested case-control study

Abstract Study question Is there an association between odds of achieving pregnancy and high-normal/elevated TSH levels in sub-clinical hypothyroid (SCH) patients on levothyroxine replacement who are undergoing IVF? Summary answer Odds of achieving pregnancy are significantly greater when TSH on day of beta-hCG is elevated/high-normal despite levothyroxine replacement in sub-clinical hypothyroid (SCH) patients undergoing IVF. What is known already TSH levels are known to increase following ovarian stimulation (OS). A 2023 Nature publication reported that in euthyroid patients undergoing fresh embryo transfer following OS and IVF, elevated/high-normal TSH levels (>2.5 mIU/mL) are associated with better pregnancy rates. Another recent study found no differences in IVF outcomes between SCH patients whose TSH was maintained=/< 4.2 mIU/mL on levothyroxine vs euthyroid controls. To the best of our knowledge, there are no prospective studies investigating possible association between pregnancy outcome and elevated TSH levels following OS within a cohort of SCH patients on levothyroxine replacement, using 2.5 mIU/mL as a strict cut-off. Study design, size, duration Nested case-control study performed between July-December 2023. PCOS and other endocrinopathies excluded. 100 SCH patients booked for fresh, blastocyst eSET cycles initially recruited after thyroxine replacement. 79 patients completed the study following 5 drop-outs and 16 cases of cycle cancellation/failure, cleavage-stage transfers and freeze-all. Odds of achieving pregnancy (‘cases’) in patients with elevated/high-normal TSH (‘exposure’) on day of beta-hCG determined by Odds Ratio, with beta-hCG negative patients serving as ‘controls’. First IVF cycle data analysed/presented. Participants/materials, setting, methods Study performed at an university-affiliated ART institute. Following institutional ethical clearance, patients with SCH (TSH>2.5 mIU/mL) recruited after informed consent. Levothyroxine replacement initiated to achieve TSH:0.5-2.5 mIU/mL and continued; followed by OS, antagonist IVF/ICSI cycles, hCG trigger and fresh blastocyst eSET. TSH measured again on day of beta-hCG (blinded). Odds Ratio calculated (IBM SPSS V.26) to determine odds of achieving pregnancy in high-normal/elevated group (TSH>2.5 mIU/mL) compared to low-normal group (TSH =/< 2.5 mIU/mL). Main results and the role of chance Baseline demographic characteristics of the single starting cohort of sub-clinical hypothyroid patients undergoing IVF/ICSI (n = 79) are summarized as mean±SD- age: 31.7±4.9 years, BMI: 27.9±14.2 kg/m2, AMH: 3.1±2.4 ng/mL, TSH before levothyroxine replacement: 5.5±2.7 mIU/mL. Data analysis showed that out of 63 patients in whom TSH level elevated > 2.5 mIU/mL on day of beta-hCG, 33 became pregnant (P.R- 52.4%); and out of 16 patients in whom TSH remained =/< 2.5 mIU/mL on day of beta-hCG, 3 became pregnant (P.R- 18.8%). Statistical analysis further revealed that odds of achieving pregnancy in elevated/high-normal TSH group was almost 5 times compared to odds of achieving pregnancy in low-normal TSH group (OR = 4.77, C.I= 1.24-18.37, at 95% confidence), considering TSH values on day of beta-hCG. Mean TSH in pregnant group (n = 36) was also found to be higher (4.2±1.6 mIU/mL) than mean TSH (3.9±1.9 mIU/mL) in those who did not get pregnant (n = 43). Limitations, reasons for caution Our study is limited by its modest sample size and adequately powered, larger prospective studies are needed before definite conclusions can be drawn from our data. Moreover, being an ongoing study, we do not yet have miscarriage and live-birth data for all patients and thus have not reported the same. Wider implications of the findings To our knowledge, this is the first prospective study documenting association between positive pregnancy outcome and high-normal TSH (using TSH>2.5 mIU/mL as cut-off) in SCH patients having fresh blastocyst eSET. Further investigation is required to determine if high-normal TSH following OS has protective impact on IVF, and its underlying mechanism. Trial registration number not applicable

Thyroid disfunction and obesity - what comes first? A complex relationship between hypothyroidism and weight gain

Introduction: Obesity and mild thyroid failure are common diseases, and the complex relationship between thyroid function and excess weight gain is still being researched. This study analyzes and summarizes the current scientific reports on the intricate correlation between thyroid dysfunction and obesity. Material and methods: We have gathered the available materials and scientific reports, analyzing and summarizing them in a single study. Aim of study: We aimed to summarize the studies conducted so far by analyzing the available scientific reports to answer the question of ‘what comes first’ and to understand the correlation between thyroid dysfunction and excessive weight gain. Discussion: Thyroid dysfunction in the form of hypothyroidism is associated with metabolic abnormalities, which may play a crucial role in the development of metabolic syndrome. On the other hand, excess level of leptin associated with excess adipose tissue is a potential cause of disruptions in the hypothalamic-pituitary-thyroid axis, manifested as elevated TSH levels. Therefore, it is worth considering certain aspects regarding the inclusion of hormone replacement therapy in obese patients presenting laboratory features of subclinical hypothyroidism. Conclusion. Obesity-induced thyroid dysfunction is typically reversible with weight loss and hormone replacement therapy should be considered for obese patients with subclinical hypothyroidism only if thyroid antibodies are present to confirm an autoimmune thyroid disorder.

Risks of Iodine Excess.

Iodine is a micronutrient that is required for thyroid hormone synthesis. The iodide cycle in thyroid hormone synthesis consists of a series of transport, oxidation, organification, and binding/coupling steps in thyroid follicular cells. Common sources of iodine include the consumption of an iodine-rich diet or iodine fortified foods, the administration of amiodarone, iodine-containing supplements, or iodinated contrast media, and other miscellaneous sources. Methods to assess population iodine status include the measurement of urinary iodine concentrations, blood thyroglobulin levels, prevalence of elevated neonatal TSH levels, and thyroid volume. Although excessive iodine intake or exposure is generally well tolerated, an acute iodine load may result in thyroid dysfunction (hypothyroidism or hyperthyroidism) in certain susceptible individuals due to the failure to escape from the Wolff-Chaikoff effect and to the Jod-Basedow phenomenon, respectively. In this review, we discuss the associations between excessive iodine intake or exposure, with particular focus on iodinated contrast media as a common source of excess iodine in healthcare settings, and risks of incident thyroid dysfunction. We also summarize the risks of iodine excess in vulnerable populations and review current guidelines regarding the screening and monitoring of iodinated contrast-induced thyroid dysfunction. Finally, we discuss the long-term potential nonthyroidal health risks associated with iodine excess and suggest the need for more data to define safe upper limits for iodine intake, particularly in high-risk populations.

Effect of TSH on aromatase expression of ovarian granulosa cells in obese mice.

Aromatase plays an important role in ovarian development, the normal progress of the menstrual cycle, and fertility status. Elevated aromatase activity is linked to obesity. There is a bidirectional relationship between obesity and thyroid function. Few studies have investigated the relationship between TSH and ovarian aromatase in obesity. Our aim was to investigate the effect of TSH on aromatase expression of ovarian granulosa cells in obese mice. Female mice pups were divided into an obesity group and a control group. Obese parameters and the time of pubertal onset were recorded. At the age of 5weeks, blood and tissues were obtained. Serum aromatase and hormone concentrations were measured using ELISA. The granulosa cells were isolated and exposed to variable concentrations (0μM, 1μM, 10μM, 100μM) of TSH. The expression of CYP19A1 mRNA and protein were assessed via RT-qPCR and western blot. In female mice, body weight, Lee's obesity index, and serum levels of E2, aromatase, and TSH were significantly higher in the obesity group compared to the control group, whereas the time of pubertal onset and serum T3 and T4 concentrations were significantly lower (all P < 0.001). In granulosa cells, the expression of CYP19A1 mRNA in the obesity group was lower than that in the control group at 1μM and 100μM concentrations of TSH (both P < 0.001). The expression of CYP19A1 protein in the obesity group was higher than that in the control group after TSH stimulation (P = 0.014, P < 0.001, and P = 0.004, respectively). With the increase of TSH concentrations, the expression of CYP19A1 mRNA and protein in the two groups significantly increased (all P < 0.001). Early puberty and elevated serum aromatase and TSH levels were found in obese female mice. In the granulosa cells of obese mice, TSH directly regulates aromatase expression in a dose-dependent manner.

Association between the triglyceride-glucose index and thyroid disorders: a cross-sectional survey and Mendelian randomization analysis.

Metabolic diseases are associated with thyroid disorders. Insulin resistance is the common pathological basis of metabolic diseases. We explored the relationship between the triglyceride-glucose (TyG) index, a simple insulin-resistance marker, and thyroid disorders. Eligible TIDE (Thyroid Diseases, Iodine Status and Diabetes Epidemiology) subjects (n = 47,710) were screened with inclusion/exclusion criteria. Thyroid disorder prevalence among different TyG index groups was stratified by sex. Logistic regression evaluated the correlation between the TyG index and thyroid disorders. Multiple linear regression evaluated the association between the TyG index and TSH. Additionally, two-sample Mendelian randomization (MR) using published genome-wide association study data evaluated causality in the association between the TyG index and TSH. Men and women with greater TyG indices had a significantly greater prevalence of thyroid disorders than individuals with the lowest quartile (Q1) of TyG index (p < 0.05). Following adjustment for confounding factors, we observed that a greater TyG index significantly increased the risk of subclinical hypothyroidism in men and women (men: Q2: odds ratio (OR) [95% confidence interval (CI)] = 1.22 [1.07-1.38], p = 0.002; Q3: OR [95% CI] = 1.28 [1.12-1.45], p < 0.001; Q4: OR [95% CI] = 1.29 [1.12-1.50], p = 0.001; women: Q2: OR [95% CI] = 1.25 [1.12-1.39], p < 0.001; Q3: OR [95% CI] = 1.47 [1.31-1.64], p < 0.001; Q4: OR [95% CI] = 1.61 [1.43-1.82], p < 0.001). Only among women was the highest TyG index quartile associated with hypothyroidism (OR [95% CI] = 1.70 [1.15-2.50], p = 0.007). Additionally, in men, the association exists only in the more than adequate iodine intake population. In women, the relationship between the TyG index and thyroid disorders disappears after menopause. Furthermore, the TyG index exhibited a linear positive correlation with TSH levels. The MR analysis results revealed a causal relationship between a genetically determined greater TyG index and increased TSH (inverse-variance weighting (IVW): OR [95% CI] = 1.14 [1.02-1.28], p = 0.020); however, this causal relationship disappeared after adjusting for BMI in multivariable MR (MVMR) analysis (MVMR-IVW: OR 1.03, 95% CI 0.87-1.22, p = 0.739). A greater TyG index is associated with hypothyroidism and subclinical hypothyroidism and varies by sex and menopausal status. MR analysis demonstrated that the causal relationship between a genetically determined greater TyG index and elevated TSH levels is confounded or mediated by BMI.

To study thyroid profile in CKD patients in Eastern Uttar Pradesh

Chronic kidney disease (CKD) remains a universal pandemic that has evolved into a serious public health problem that imposes a significant socioeconomic burden. Thyroid profile is disrupted in CKD patients due to aberrant thyroid hormone metabolism. The purpose of our study was to assess thyroid function in people who had chronic renal disease (CKD).According to the inclusion-exclusion criteria, this cross-sectional observational research enrolled 150 chronic renal disease patients.All patients who met the above criteria underwent a detailed history as well as a general and systemic examination. Thyroid function tests, USG entire abdomen, chest X-ray, ECG, and 2D Echocardiogram, were performed. There were 84 men and 66 women among the 150 CKD patients. Thyroid hormone abnormalities were found in 93.3 % of the individuals. 14.7 % of the participants had hypothyroidism, 14.7 % had low T3 and T4 readings, 10% had low T4 values alone, 38 % had low T3 only, and 17% had subclinical hypothyroidism. Low T3 levels (58 %) were the most prevalent thyroid anomaly, with or without low T4 or elevated TSH levels. Low T3 levels were more common in patients with advanced CKD.Thyroid hormone abnormalities are linked to different stages of chronic renal disease.

Relationship between thyroid function changes with work-/night-shifts and history of thyroid pathology among health personnel

The study aim was to analyze the relationship between functional thyroid pathology and the exposure to work shifts / night shifts, and describe the most prevalent thyroid disorders based on the type of shift. Cross-sectional study performed in the emergency department of a hospital in Almeria (Spain). Relationships between thyroxine and thyrotropin levels (TSH) and work shifts, professional category and history of thyroid pathology were analyzed. The study included 133 workers; 80.5% female, average age was 46.11 years (38 - 65), and 52% were part of the nursing staff; thyroid disorders were more frequent in female participants. Most participants (81.2%) had rotating shifts schedules and 11.3% night shifts (12.1% female and 7.7% male). Thyroid alterations were found in 27% of the participants (usually elevated TSH levels and normal thyroxine levels), particularly in those doing night shifts (61.1%). TSH alterations were more frequent in individuals doing night shifts than in rotating shifts (53.3 vs 13.0%; p<0.001). Individuals working night shifts had mean TSH values in the normal range, although significantly higher than the individuals in the rest of the shifts; thyroxine levels were found to be similar. No thyroid disorders were found in day shift participants. Night shift and a history of thyroid pathology were independent predictors of thyroid disorders. Night shift schedules and history of thyroid disorders are more frequent in female, both related to the presence of thyroid disorders, indicating the need to include the evaluation of these disorders in health surveillance programs and analyze gender differences.

Parameters of PCOS in Tertiary Hospital in Bangladesh

Background: Polycystic ovarian syndrome (PCOS) represents a complex endocrinopathy with significant metabolic implications. The Rotterdam criteria establish the diagnosis based on the presence of two of three criteria: ultrasound-confirmed polycystic ovaries, hyperandrogenism, and persistent anovulation. Objective: Our objective was to investigate hormonal and anthropometric parameters in PCOS patients compared to controls, aiming to elucidate predictive markers and metabolic aberrations. Method: A case-control study comprising 50 PCOS subjects and 50 controls was conducted, focusing on females aged 18-40 attending an obstetrics and gynecology department, Tertiary hospital. Hormonal assays and anthropometric measurements were performed following strict inclusion and exclusion criteria. Results: Significant differences emerged between PCOS and control groups across various parameters. PCOS individuals displayed elevated levels of TSH, LH, FSH, and prolactin, coupled with increased BMI and altered waist-to-hip ratio, indicating early metabolic disruptions. Notably, the LH:FSH ratio was lower in PCOS subjects, suggesting hormonal imbalances. Conclusion: High levels of thyroid-stimulating hormone, LH, FSH, and prolactin, coupled with elevated body mass index and waist-to-hip ratio, served as indicators of PCOS and early metabolic irregularities.

Female rats present higher oxidative damage and inflammation during goitrogenesis.

Thyroid disorders affect more women than men, but the underlying mechanisms contributing to this disparity remain incompletely understood. Thyrotropin (TSH), the primary regulator of thyroid oxidative hormonogenesis, has been implicated as a risk factor for proliferative thyroid diseases and a predictor of malignancy. In this study, we aimed to evaluate the impact of sustained elevated TSH levels on thyroid redox homeostasis, inflammatory markers, and DNA damage response in both male and female rats. Rats were treated with methimazole for 7 or 21 days, and hormonal measurements were conducted. H2O2 levels were evaluated in thyroid membrane fractions, while enzymatic activities were assessed in total thyroid homogenates. Sex-specific differences emerged, with females displaying higher reactive oxygen species levels - increased transiently NOX and sustained DUOX activities. Lipid peroxidation marker 4-hydroxynonenal (4-HNE) was elevated in females at both time points, contrasting with males just at 21 days. Sexual dimorphism was observed in DNA damage response, with females showing higher γH2AX levels at 21 days. Elevated IL-1β, TNF-α, CD11b mRNA, and phospho-NF-κB levels at 7 days indicated a distinct inflammatory profile in females. Notably, both sexes exhibited upregulated antioxidant enzymes. Our data suggest that females are more susceptible to oxidative damage and inflammation in our goiter model, which may be associated with higher ROS production and a less-efficient antioxidant defense system. These findings provide insights into the sex-specific mechanisms underlying thyroid dysfunction and highlight the importance of considering sex disparities in thyroid disorder research.

Autoimmune thyroid disease and myasthenia gravis: a study bidirectional Mendelian randomization.

Previous studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains uncertain. Therefore, we employed a Mendelian randomization (MR) analysis to investigate the causal relationship between AITD and MG. To explore the interplay between AITD and MG, We conducted MR studies utilizing GWAS-based summary statistics in the European ancestry. Several techniques were used to ensure the stability of the causal effect, such as random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated by calculating Cochran's Q value. Moreover, the presence of horizontal pleiotropy was investigated through MR-Egger regression and MR-PRESSO. The IVW method indicates a causal relationship between both GD(OR 1.31,95%CI 1.08 to 1.60,P=0.005) and autoimmune hypothyroidism (OR: 1.26, 95% CI: 1.08 to 1.47, P =0.002) with MG. However, there is no association found between FT4(OR 0.88,95%CI 0.65 to 1.18,P=0.406), TPOAb(OR: 1.34, 95% CI: 0.86 to 2.07, P =0.186), TSH(OR: 0.97, 95% CI: 0.77 to 1.23, P =0.846), and MG. The reverse MR analysis reveals a causal relationship between MG and GD(OR: 1.50, 95% CI: 1.14 to 1.98, P =3.57e-3), with stable results. On the other hand, there is a significant association with autoimmune hypothyroidism(OR: 1.29, 95% CI: 1.04 to 1.59, P =0.019), but it is considered unstable due to the influence of horizontal pleiotropy (MR PRESSO Distortion Test P < 0.001). MG has a higher prevalence of TPOAb(OR: 1.84, 95% CI: 1.39 to 2.42, P =1.47e-5) positivity and may be linked to elevated TSH levels(Beta:0.08,95% CI:0.01 to 0.14,P =0.011), while there is no correlation between MG and FT4(Beta:-9.03e-3,95% CI:-0.07 to 0.05,P =0.796). AITD patients are more susceptible to developing MG, and MG patients also have a higher incidence of GD.

Thyroid Disorders in Systemic Sclerosis: A Comprehensive Review.

Systemic sclerosis, also referred to as scleroderma, is a chronic autoimmune disease that affects both internal organs and the skin. Systemic sclerosis predominantly affects female patients and can coexist with other disorders, including those affecting the thyroid gland. Common symptoms such as fatigue and weight changes can be attributed to either systemic sclerosis or thyroid disease. In this comprehensive review, an extensive analysis is conducted using research from 2002 to 2022, sourced from PubMed. The main focus of this exploration is to understand the intricate relationship between thyroid disorders and systemic sclerosis. We obtained these results by analyzing a number of 32285 patients included in 21 original studies. The existing evidence suggests that there is a higher incidence of elevated TSH levels and hypothyroidism in patients with systemic sclerosis, particularly in females, compared to the general population. This remains true even when comparing patients from iodine-deficient regions. Additionally, there is an increased occurrence of hyperthyroidism in the context of systemic sclerosis, which negatively impacts the prognosis of these patients. Furthermore, thyroid antibodies, predominantly anti-thyroid peroxidase (anti-TPO) antibodies, and autoimmune disorders are more commonly observed in individuals with systemic sclerosis. Although thyroid nodules are not specifically linked to the disease, when considering thyroid volume, it is observed that the thyroid gland in systemic sclerosis patients has a decreased volume, possibly due to fibrosis. Conversely, other studies have revealed that patients without autoimmune thyroid diseases (AITDs) are more likely to have a history of digital ulcers, pulmonary fibrosis detected by computed tomography scan, and a requirement for immunosuppressive medication. The majority of the studies did not establish a connection between thyroid disease in these patients and the occurrence of the limited or diffuse forms of systemic sclerosis, as well as the presence of digital ulcers, calcinosis, pulmonary arterial hypertension, scleroderma renal crisis, Raynaud phenomenon, and various other clinical manifestations.

Thyrotropin induces atherosclerosis by upregulating large conductance Ca2+-activated K+ channel subunits

Hypothyroidism is associated with elevated levels of serum thyrotropin (TSH), which have been shown to promote abnormal proliferation of vascular smooth muscle cells and contribute to the development of atherosclerosis. However, the specific mechanisms underlying the TSH-induced abnormal proliferation of vascular smooth muscle cells remain unclear. The objective of this study was to investigate the role of TSH in the progression of atherosclerosis. Our research findings revealed that hypothyroidism can trigger early atherosclerotic changes in the aorta of Wistar rats. In alignment with our in vitro experiments, we observed that TSH induces abnormal proliferation of aortic smooth muscle cells by modulating the expression of α and β1 subunits of large conductance Ca2+-activated K+ (BKCa) channels within these cells via the cAMP/PKA signaling pathway. These results collectively indicate that TSH acts through the cAMP/PKA signaling pathway to upregulate the expression of α and β1 subunits of BKCa channels, thereby promoting abnormal proliferation of arterial smooth muscle cells. These findings may provide a basis for the clinical prevention and treatment of atherosclerosis caused by elevated TSH levels.