Normal Thyroid-stimulating Hormone Research Articles

Management of immune-checkpoint inhibitor (ICI)-related thyroid dysfunction: An avenue for quality improvement.

309 Background: Hypothyroidism is a common immune-related adverse effect (irAE) with ICI therapy, occurring in 4-9% of patients treated with PD-1 ICI, and 10-15% of patients treated with dual PD-1/CTLA-4 ICI therapy. Prolonged thyroid dysfunction increases risk for cardiovascular and cerebrovascular events. Consensus guidelines recommend weight-based dosing for thyroid repletion in younger patients and/or without cardiovascular comorbidities. We observed that patients on thyroid repletion are often underdosed compared to guideline recommendations. To formally evaluate this, we performed a retrospective study to determine the percentage of ICI-treated cancer patients who are receiving guideline-recommended thyroid repletion at an urban comprehensive cancer center. Methods: We identified patients who received PD-1 ICI, either singly or in combination with chemotherapy, TKI, or other ICI to identify patients who met the consensus guideline criteria for weight-based dosing of thyroid repletion. Analysis was restricted to ICI-treated patients who had a thyroid stimulating hormone (TSH) level above 10 mU/L following initiation of therapy. For each patient, we collected the patient’s age, weight, and initial prescribed dose of levothyroxine. We also obtained the date of abnormality and normalization for TSH and free thyroxine (T4). Results: 402 patients received ICI, either singly or in combination. 55 patients had TSH > 10 mU/L. 15 patients who did not have documentation of hypothyroidism or developed it prior to immunotherapy were excluded. The proportion of patients who were eligible for, and who received weight-based repletion is summarized in the table. The proportion of patients who received guideline-recommended thyroid repletion was: 6/17 (35%) SITC-guideline recommended dose, 18/27 (67%) NCCN-guideline recommended dose and 6/22 (28%) ASCO-guideline recommended dose. The median time to free T4 normalization was 9 weeks (IQR 6-15 weeks) and TSH normalization was 13 weeks (IQR 9-30 weeks). Conclusions: At an urban comprehensive cancer center, the incidence of hypothyroidism in ICI-treated cancer patients is 10%. The compliance with guideline recommended weight-based dosing is low, with 33-72% of patients not receiving appropriate therapy, translating into prolonged time to thyroid function normalization. We aim to develop a quality improvement intervention to improve thyroid dosing in this patient population. Proportion of patients receiving guideline-recommended thyroid repletion. Criteria Per SITC Guidelines Per NCCN Guidelines (if lower end of dosing range) Per ASCO Guidelines Patients eligible for weight-based dosing 17 27 22 # of patients who received appropriate initial dosing 6 (35%) 18 (67%) 6 (28%) Average initial dose prescribed 81 mcg 78 mcg 76 mcg Average initial dose per guidelines (based on ideal body weight) 107 mcg 71 mcg 109 mcg

The Association Between Hypothyroidism and Cognitive Function Change in Women across the Menopause Transition: The Study of Women's Health Across the Nation.

Background: Patients treated for hypothyroidism with levothyroxine (LT4) monotherapy may present with persistent hypothyroidism symptoms, including cognitive symptoms, despite having a normal thyroid stimulating hormone (TSH) level. It remains unclear whether LT4 monotherapy is sufficient to normalize cognitive function outcomes over time. Methods: This is a multisite longitudinal study of a diverse group of women during midlife representing 5 ethnic/racial groups from 7 enrollment sites across the United States in the Study of Women's Health Across the Nation. Women were screened for a history of thyroid disease and the use of LT4. The study consisted of two primary groups: women with LT4-treated hypothyroidism and control women without thyroid disease. Each participant completed up to 9 cognitive assessments over the study period testing processing speed, working memory, and episodic memory (immediate and delayed recall). Multivariable generalized linear mixed models of scores for each cognitive assessment were developed to determine the association between LT4-treated hypothyroidism and cognitive function trajectories. Covariates included sociodemographic, clinical characteristics, and menopausal status (pre/early peri, late peri, and surgical/post). Sensitivity analyses were conducted to assess the impact of abnormal TSH levels and practice effects (i.e., improvements in scoring after repeated testing). Results: Of the 2033 women who were included in the study, 227 (11.2%) met criteria for LT4-treated hypothyroidism. At baseline, both processing speed and working memory scores were higher in LT4-treated women (mean processing speed scores: 56.5 vs 54.4; p value = 0.006; mean working memory scores: 6.8 vs 6.4; p value = 0.018). However, when considering the effect of LT4-treated hypothyroidism over time, there were no significant differences in the rate of cognitive decline (in any measure) between the hypothyroidism and control groups with or without covariate adjustment. The results were similar when considering LT4-treated women with abnormal TSH levels or after minimizing practice effects. Conclusions: We observed no difference in cognitive decline between women with LT4-treated hypothyroidism and women without thyroid disease. For similar aged patients with cognitive complaints, if thyroid function testing is normal, clinicians should consider causes other than inadequate thyroid hormone treatment to explain these symptoms.

A confusing situation in the clinic: isolated maternal hypothyroxinemia

Isolated maternal hypothyroxinemia (IMH) is a common problem in the clinic. There is a normal maternal thyroid stimulating hormone (TSH) level with a low maternal free thyroxine (FT4) level. The aim of this review is to explain IMD in the light of current literature and to contribute to clinicians in the management of IMH. Iodine deficiency is the most important factor in etiology. The effects of IMH on the pregnant woman and the fetus are not clear. However, it is a serious concern among serious clinicians, especially considering the importance of the effect of thyroid hormones on fetal brain development. As for the treatment of IMH, the number of studies conducted is not sufficient and there is no consensus and evidence on levothyroxine treatment. However, there is a consensus on iodine supplementation and it is recommended to take 250 mg of iodine daily. As a result, IMH is a problem that should be taken seriously during pregnancy and care should be taken regarding its diagnosis and treatment. Additionally, more research is needed on the effects and treatment of IMH on pregnant and fetal health

Analysis of Inflammatory and Thyroid Hormone Levels Based on Hepatitis A and B Virus Immunity Status: Age and Sex Stratification.

This study investigated the potential associations between hepatitis virus antibody status and thyroid and inflammatory function. The C-reactive protein (CRP), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were measured in individuals with and without antibodies to the hepatitis A virus (HAV) and hepatitis B virus (HBV). Participants were stratified by age, sex, and HAV/HBV antibody status. Participants with and without antibodies to HAV and HBV had normal CRP, TSH, and FT4 levels. However, notable discrepancies were observed in FT4 levels among participants with HAV antibodies and in CRP and FT4 levels among those with both HAV and HBV antibodies, suggesting potential associations between viral immunity and thyroid function, especially in younger participants. Significant variations in thyroid hormone levels were noted when the sample was stratified by sex and HAV and HBV antibody status, indicating that the association between antibody status and thyroid hormone levels varied by sex. This study underscores the need for further research on the effect of viral immunity on inflammatory parameters and thyroid hormone levels.

The importance and prognostic effect of thyroid hormones in patients with transposition of the great arteries

Objectives: Transposition of the great arteries (TGA) is a rare congenital heart disease that occurs in 3 in 10,000 newborns and is rapidly fatal (90%) within one year if left untreated. The prognosis of this pathology changed after introducing an early arterial switch operation (ASO), while the left ventricle could still adapt to systemic high-pressure conditions. Appropriate regulation of thyroid hormones positively impacts metabolism, cardiac function, and postoperative recovery. Therefore, regular thyroid hormone monitoring and thyroid function monitoring of TGA patients may help to improve the health status and prognosis of this group of postoperative patients. Methods: In our study, 127 patients who underwent ASO at our pediatric cardiac surgery clinic between 01.01.2014 and 18.09.2021 were retrospectively analyzed and included. Among the patients, 43% (n=54) were females, and 57% (n=73) were males. Results: The coronary arteries were normal in 89.7% (n=114) and abnormal in 10.3% (n=13) of the patients. Twenty-one of the patients exited, and mortality was calculated to be 16.5%. There were no significant differences in mortality or thyroid stimulating hormone (TSH), free thyroxine (T4), or free triiodothyronine (T3) values (P=0.674, P=0.345, P=0.478). In our study, in which we investigated the effect of thyroid hormone levels on prognosis in neonatal patients with TGA with normal free T3, T4, and TSH values, we found that TSH levels were greater in the group with advanced aortic regurgitation and exitus, although the effect of thyroid hormones on postoperative results was not statistically significant. Conclusions: Congenital hypothyroidism is a common disease with cardiac effects. During the neonatal period, this disease may conceal itself. Careful, expert clinical follow-up and clinical trials are crucial to improve outcomes in the surgical treatment of transposition of the great arteries, a complex congenital heart disease.

The influence of calibration on bias in quality control and patient results for TSH on Vitros XT 7600 analyzer.

Thyroid-stimulating hormone (TSH) is a glycoprotein secreted by the anterior pituitary gland and is regulated by negative feedback from the serum free thyroid hormones. In this study we aimed to quantitate the relative bias caused by calibration drifting as seen in our TSH Levey-Jennings quality control (QC) charts and assess the magnitude of bias on patients' samples. In the period from October 2021 to August 2022 we looked at the QC results of ten 28-days' calibration time intervals and calculated relative bias compared to the mean. For each time interval the mean from three QC points before and after calibration was calculated. The average from 10 pre- and post-calibration means was calculated and the relative bias, pre- and post-calibration, was then calculated. We used 5 patient samples with low, normal and high TSH concentrations and calculated relative bias pre- and post-calibration. The allowed relative bias for TSH is ± 6.7%. At both QC levels, with the respective means of 5.14 mIU/L (coefficient of variation, CV% = 3.1%) and 27.80 mIU/L (CV% = 3.2%) had their respective relative bias - 8.2% and - 7.9%. The patient samples with low (0.586 mIU/L), normal (2.89 mIU/L and 5.19 mIU/L) and high (20.5 mIU/L and 39.8 mIU/L) TSH had - 4.1%, - 4.0%, - 3.5%, - 5.1% and - 4.1%, respectively. Even though the relative bias exceeded allowable criteria for the QC samples, this was not manifested on the patients' samples.

Association Between Particulate Matter Exposure and Preterm Birth in Women With Abnormal Preconception Thyrotropin Levels: Large Cohort Study.

Prior research has linked exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) with preterm birth (PTB). However, the modulating effect of preconception thyroid stimulating hormone (TSH) levels on the relationship between PM2.5 exposure and PTB has not been investigated. This study aimed to assess whether preconception TSH levels modulate the impact of PM2.5 exposure on PTB. This cohort study was conducted in Guangdong, China, as a part of the National Free Pre-Pregnancy Checkups Project. PM2.5 exposure was estimated by using the inverse distance weighting method. To investigate the moderating effects of TSH levels on trimester-specific PM2.5 exposure and PTB, we used the Cox proportional hazards model. Additionally, to identify the susceptible exposure windows for weekly specific PM2.5 exposure and PTB, we built distributed lag models incorporating Cox proportional hazards models. A total of 633,516 women who delivered between January 1, 2014, to December 31, 2019, were included. In total, 34,081 (5.4%) of them had abnormal preconception TSH levels. During the entire pregnancy, each 10-μg/m3 increase in PM2.5 was linked to elevated risks of PTB (hazard ratio [HR] 1.559, 95% CI 1.390-1.748), early PTB (HR 1.559, 95% CI 1.227-1.980), and late PTB (HR 1.571, 95% CI 1.379-1.791) among women with abnormal TSH levels. For women with normal preconception TSH levels, PM2.5 exposure during the entire pregnancy was positively associated with the risk of PTB (HR 1.345, 95% CI 1.307-1.385), early PTB (HR 1.203, 95% CI 1.126-1.285), and late PTB (HR 1.386, 95% CI 1.342-1432). The critical susceptible exposure windows were the 3rd-13th and 28th-35th gestational weeks for women with abnormal preconception TSH levels, compared to the 1st-13th and 21st-35th gestational weeks for those with normal preconception TSH levels. PM2.5 exposure was linked with a higher PTB risk, particularly in women with abnormal preconception TSH levels. PM2.5 exposure appears to have a greater effect on pregnant women who are in the early or late stages of pregnancy.

A Critical Investigation of Sick Euthyroid Syndrome in Chronic Heart Failure Patients: Addressing the Need for Accurate Thyroid Assessment.

Background The body undergoes numerous metabolic changes during severe illness or physiological stress to protect itself by lowering metabolism and reducing overall demands. This evolutionary adaptation dates back to early human development, long before the advent of ICU facilities and advanced treatments. One such protective mechanism is Sick Euthyroid Syndrome (SES), also known as Non-thyroidal Illness Syndrome (NTIS). SES commonly occurs in critically ill patients and is frequently observed in conditions such as heart failure, chronic kidney disease, and severe sepsis. This syndrome is characterized by abnormal thyroid function tests in patients with acute or chronic systemic illnesses who do not have intrinsic thyroid disease. Typically, these patients exhibit low serum levels of triiodothyronine (T3), normal or low levels of thyroxine (T4), and normal or low thyroid-stimulating hormone (TSH) levels. SES is believed to be an adaptive response to illness, aimed at reducing the body's metabolic rate and conserving energy during severe physiological stress. This original article delves into SES's prevalence and clinical impact in these settings. Materials and methods The study aims to determine the prevalence of SES in patients with long-standing heart failure, elucidate the relationship between thyroid function and heart failure severity, and assess its impact on various hematological and clinical parameters. This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India, a 2011-bed hospital, over one and a half years. This study included 70 patients with chronic heart failure, aged 18 years and above, defined by a left ventricular ejection fraction of 40% or less and a Boston criteria score of 8 or more. Patients were excluded if they had a history of thyroid dysfunction, clinical sepsis, or were taking thyroid-affecting drugs. Results The study provides important insights into the prevalence and impact of SES in long-standing heart failure patients. It found that a significant 44.29% of these patients exhibited low T3 levels, highlighting the substantial occurrence of SES in this population. Additionally, the study revealed a negative correlation between N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels, Boston score, and total T3, suggesting that as indicators of heart failure severity worsen, total T3 levels may decrease further. Another key finding is the high prevalence of anemia among heart failure patients, with a notable gender disparity: 92.11% of male patients were affected compared to 50% of female patients. Conclusion The study concluded that SES is significantly prevalent among long-standing heart failure patients, further indicating that thyroid suppression increases with the severity of heart failure. Recognizing SES can guide tailored treatments, prompting intensive monitoring and optimized heart failure management.Additionally, the study found a high prevalence of anemia, particularly among male patients, highlighting the need for gender-specific considerations in managing heart failure. These findings underscore the importance of routine thyroid function assessments and regular monitoring of anemia in heart failure patients. Future research should focus on improving clinical outcomes through comprehensive management of both thyroid function and anemia in these patients.

Epidemiologic changes in thyroid disease.

To analyze the evolving epidemiologic trends in thyroid disease, focusing on risk factors, underlying drivers of these changes, and their implications on clinical practice and research priorities. Thyroid disease remains one of the most prevalent groups of disorders globally, and the shift in its frequency and distribution is multifactorial. The prevalence of hypothyroidism increases with age, although normal thyrotropin ranges appear to be age-dependent, raising concern for potentially inappropriate levothyroxine use. Hyperthyroidism and Graves' disease continue to be predominant in reproductive-age women but exhibit a milder phenotype at diagnosis. Thyroid nodules are increasingly found in asymptomatic patients, likely from more widespread use of neck and chest imaging. Thyroid cancer incidence has risen exponentially over the years, mostly driven by overdiagnosis of low-risk tumors; however, a small rise in incidence of higher risk tumors has been noted. Obesity appears to be a risk factor for thyroid cancer occurrence and more aggressive forms of the disease. Understanding epidemiologic trends in thyroid disease is crucial for guiding clinical practice and research efforts, aiming to optimize patient outcomes while preventing unnecessary and potentially harmful interventions.

The role of non-invasive oscillometric method to detect aortic stiffness in patients with subclinical hypothyroidism

Introduction Subclinical hypothyroidism (SCH) is a biochemical condition that is diagnosed when peripheral free thyroid hormone levels are within normal reference laboratory range but serum thyroid-stimulating hormone (TSH) levels are mildly elevated. The aim of this study was to investigate the relationship between SCH and arterial stiffness using two different non-invasive methods, including echocardiography and oscillometric arteriography. Material and Methods The study included 33 newly diagnosed SCH patients and 34 age- and gender-matched healthy controls. Systolic and diastolic diameters and elastic parameters of the aorta were calculated by 2D Transthoracic echocardiography (TTE). Central blood pressure and aortic stiffness values of patient groups were measured noninvasively from the brachial artery using Mobil-O-Graph arteriography. Pulse wave velocity (PWV) and augmentation index (AIx) were used as arterial stiffness indicators. Results There was no significant difference between SCH and control groups with regard to age, gender, and body mass index (BMI). Aortic strain and aortic distensibility, were significantly lower in the SCH group than in the control group (p < 0.001). PWV and AIx which measured by Mobil-O-Graph arteriography were found to be significantly higher in the subclinical hypothyroid group compared to the control group (p < 0.05). Conclusion Aortic stiffness assessed by TTE and Mobil-O-Graph arteriography deteriorated in patients with SCH after excluding other cardiovascular risk factors. The assessment of aortic stiffness by the oscillometric method was easy and useful for widespread clinical use.

O-304 Is there any association between thyroid-stimulating hormone (TSH) levels and semen parameters? A retrospective study in a European fertility clinic

Abstract Study question Is there any association between TSH levels and semen parameters considering age, body mass index (BMI), and life style? Summary answer In line with the results of logistic regression, normal TSH values increase the probability of having a higher sperm count. What is known already To date, association between TSH levels, semen parameters and other hormones have not been thoroughly investigated in European andrology labs. However, while andrology guidelines do not support a systematic evaluation of thyroid function, some studies reported that men in infertility clinics have higher risks of presenting thyroid disorders than in the general population. Study design, size, duration Both partners investigated for sterility are routinely checked for TSH in the work up of our clinic. We examined for 2021 – 2023 all 347 male patients (infertile/fertile) with complete records of demographic data, semen analysis and hormone analysis. Patients suffering from azoospermia, genital tract infections, hormonal supplementation or heavy medical treatments (radiotherapy, chemotherapy), as well as those receiving iodine supplements or drugs that could potentially affect testicular or thyroid physiology, were excluded. Participants/materials, setting, methods Age, BMI, smoking and detailed alcohol intake were recorded. A blood sample was taken from each patient in connection with the sperm collection to measure TSH, FSH, LH, prolactin and testosterone levels. Spearman’s correlation coefficients were used to determine correlations among hormones. Statistical analyses were performed using semen parameters as dichotomized using WHO reference values. Men above the reference values for count, concentration and motility were used as comparison subjects in multivariate logistic regression. Main results and the role of chance The analysis explored relationships between age, BMI, smoking, alcohol consumption and semen parameters with TSH hormone levels. The mean age of the participants was 35.8 ±7.43 years and BMI was 27.2 ±4.54 kgm-2. Of all participants, 37% reported being smokers, alcohol consumption was 3% regularly, 35% occasionally, 44% rarely, 18% none. Considering a TSH level (0.4-4 mIU/l) as normal, the prevalence of thyroid dysfunction in the cohort was 0.9% (TSH &amp;lt;0.4) and 1.1% (TSH &amp;gt;4) implying that most patients had normal TSH levels. In this cohort, TSH levels were not found to be significantly affected by age, BMI, smoking or alcohol consumption despite being known as putative confounding factors influencing TSH levels. Among the various hormones evaluated, only one significant positive correlation was found between TSH and Prolactin (r = 0.199, p = 0.0001), while a trend towards a negative correlation between TSH and LH (r=-0.101, p = 0.073) was suggested. Multivariate logistic regression analysis showed, not surprisingly, that age was a factor influencing sperm count, sperm concentration as well as total and progressive sperm motility. Logistic regression also showed that when TSH values were within the normal range, sperm counts were significantly higher (OR:1.302, P = 0.043; CI95%:1.009-1.681). Limitations, reasons for caution Sperm morphology and viability were not recorded. Evaluation of thyroxine (T4) and triiodothyronine (T3) levels could be useful. The crucial role of iodine and the complex relationship between iodine and selenium status (which depends on geographical location) in affecting thyroid function should be taken into account in future studies. Wider implications of the findings Male patients with abnormal TSH levels are not very common in this region. Normal TSH level is associated with a higher sperm count. TSH assessment in infertile couples should be routine in both partners, given the recorded worldwide increase in thyroid dysfunction and iodine deficiency. Trial registration number not applicable

The association of higher thyroid stimulating hormone levels in the normal range with unexplained infertility: A cross-sectional study.

Since thyroid hormones have an essential role in energy production, early development of the human placenta, embryo development, and implantation, abnormalities in thyroid function can significantly affect pregnancy outcomes. The present study aimed to investigate the effect of higher thyroid-stimulating hormone (TSH) levels in the normal range in euthyroid women with unexplained infertility. In this cross-sectional study, we evaluated the data for 300 euthyroid women aged between 18 and 39 yr with normal TSH levels ( 5 mIU/L) referred to Yazd Reproductive Sciences Institute, Yazd, Iran from December 2018-March 2021 in 2 groups: the case group (with unexplained infertility) and the control group (with male factor infertility). Finally, age, body mass index, and serum levels of TSH were extracted from participants' medical records and compared between groups. The mean age and TSH level of participants were 31.52 3.52 yr and 1.24 2.59 mIU/L, respectively. 142 women (47.3%) had TSH 2.5, and 158 women (52.7%) had TSH 2.5 mIU/L. The women with unexplained infertility had significantly higher TSH levels than controls in the same normal range (0.62 vs. 0.64 mIU/L, p 0.001). Although a more significant proportion of women in the case group had TSH levels 2.5 mIU/L, we did not find a significant association between TSH levels and age or body mass index. Women with unexplained infertility have a higher level of serum TSH in the normal range ( 2.5 mIU/L) than the control group. So, the effect of TSH treatment on these women should be considered.

Impact of Subclinical Hypothyroidism on Lipid Profile in Jeddah: A Retrospective Cohort Study.

Background Patients with subclinical hypothyroidism (SCH) have a high serum concentration of thyroid-stimulating hormone (TSH), whereas their serum-free thyroxine concentrations are normal. Lipid metabolism is regulated in large part by thyroid hormones. It could be connected to a changed lipid profile. This study aimed to evaluate the relationship between SCH and alterations in the lipid profile. Methodology Data from 99 patients with SCH and 109 euthyroid cases were collected from King Abdulaziz Medical City, Jeddah, Saudi Arabia, from 2016 to 2022. Patients older than 18 years were included in the study. The groups were matched in terms of gender, age, and body mass index. SCH was defined as a TSH value of 4.5 to 10 mIU/L, and normal T4 as 5 to 18 μg/dL. Control cases had a normal TSH ranging from 0.45 to 4.5 mIU/L. The total serum cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels in both groups were examined and the results were recorded. Results In comparison to the control group, SCH patients had greater median glycated hemoglobin (HbA1C) (p = 0.001) and lower median vitamin D levels (p = 0.004) before therapy. Before therapy, SCH patients also showed considerably lower HDL levels and significantly higher LDL and TG levels (p < 0.001). Conclusions There is a substantial correlation between SCH and reduced HDL and vitamin D levels. It was linked to increased TG, LDL, and HbA1c levels. Only vitamin D and LDL were pathologically high. Treatment with levothyroxine raised total and LDL cholesterol levels. Future research should look into the affordability of treating SCH.

Effects of statin use on serum creatinine phosphokinase levels in normal thyroid function.

Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the effect of thyroid-stimulating hormone (TSH) levels on CPK levels after statin administration. Therefore, this study aimed to investigate CPK level alterations after statin administration according to TSH quartiles in participants with euthyroidism. This retrospective analysis included 25,047 patients with euthyroidism. CPK levels were measured before and 6 months after statin administration. Normal TSH levels were divided into four quartiles, and the CPK levels and proportions of patients with normal CPK levels after statin administration for each TSH quartile were evaluated. The baseline CPK level was significantly higher in the lowest TSH quartile (Q1) compared to the other quartiles but decreased after statin administration. Thus, the difference between the CPK levels and the other quartile groups was not significant. The proportion of patients with normal CPK levels was also significantly lowest in Q1 before statin administration; however, no significant difference was noted in the ratio among each group after statin administration. These findings were consistent with the findings of the analysis according to statin intensity. In patients in the lowest TSH quartile of the normal TSH range, the CPK level decreased, and the proportion of normal CPK levels increased significantly after statin administration. However, similar changes were not observed in other TSH quartiles. Therefore, further studies are required to mechanistically confirm these conclusions.

Investigating the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients

ABSTRACT Introduction: Effects of levothyroxine therapy on the lipid profile of hypothyroid patients lead to decrease in the risk of cardiovascular diseases and mortality. Objective: Overt or subclinical hypothyroid dysfunction has negative effects on lipid metabolism and leads to hypercholesterolemia that in turn increases the risk of cardiovascular diseases and mortality. In this matter, several interventional studies investigated the effects of levothyroxine therapy on the lipid profile of hypothyroid patients, and conflicting results have been obtained. The current research aims to investigate the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients. Methods: The present prospective study examined 112 patients (mean age of 43.80 ± 14.36 years) with overt hypothyroidism. To do so, 72.3% of patients were females. Levothyroxine replacement therapy was prescribed for patients, and they were examined monthly to evaluate the effects of therapy on their lipid profiles. After reaching normal thyroid stimulating hormone (TSH), the patients’ laboratory parameters, including TSH, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were surveyed. Results: After Levothyroxine therapy, there was a significant reduction in mean TSH (62.03 vs. 2.33 ± 1.95; P &lt; 0.0001), triglycerides (145.57 ± 88.65 vs. 121.91 ± 59.52, P = 0.002), cholesterol (203.90 ± 53.73 vs. 166.65 ± 40.07, P &lt; 0.0001), and serum LDL (123.61 ± 45.03 vs. 95.99 ± 24.20, P &lt; 0.0001), but the mean value of serum HDL did not show any significant change (54.18 ± 16.60 vs. 51.59 ± 18.38, P = 0.274). Conclusions: Levothyroxine therapy has beneficial effects on lipid profile in patients with overt hypothyroidism because it decreases serum triglyceride, total cholesterol, and LDL. However, levothyroxine therapy does not significantly change HDL levels.

TSH Trajectories During Levothyroxine Treatment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Cohort.

Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time. This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period. Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to assess within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. From the 621 LT4-treated study participants, the best-fit GMM approach identified 4 TSH trajectory classes, as defined by their relationship to the normal TSH range: (1) high-high normal TSH, (2) normal TSH, (3) normal to low TSH, and (4) low to normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 µg, P < .001). There were no significant differences in CV health markers between the classes at baseline. At least 1 significant difference in CV markers occurred in all classes, highlighted by the low to normal class, in which total and high-density lipoprotein cholesterol, triglycerides, and A1c all increased significantly (P = .049, P < .001, P < .001, and P = .001, respectively). Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes. GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. More comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes.

Triiodothyronine/Thyroxine Ratio as a Marker of Clinical Response to Levothyroxine Replacement in Patients With Hypothyroidism.

Hypothyroidism is one of the most common endocrine disorders with a simple therapy, that is levothyroxine (LT4). A normal thyroid-stimulating hormone (TSH) measurement is used as a marker of optimal replacement. But, many patients still have symptoms. Triiodothyronine (T3), thyroxine (T4), and their ratio may correlate with clinical improvement. The study aims to assess the T3/T4 ratio as a marker of clinical response in patients with hypothyroidism. Method:A cross-sectional study was conducted from June to November 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, southern Iraq. We included 48 adult patients with primary hypothyroidism on LT4 treatment only and TSH within the target reference range for at least within the last six months. Each patient was subjected to a questionnaire that was designed to capture hypothyroidism-related complaints in the form of a five-point Likert scale. Biochemical assessments were done with the measurement of TSH, T3, and T4. Despite having a normal TSH level, nearly all the patients had persistent and varying severity of clinical complaints of hypothyroidism. Tiredness, hair problems, weight gain, and cold intolerance were the most severely persistent symptoms. Patients with scores of two and more for weight gain, cold intolerance, and skin problems had significantly lower T3/T4 ratios (P = 0.04, 0.002, and 0.02, respectively), while in the remaining clinical symptoms, the T3/T4 ratio did not differ significantly. A low T3/T4 ratio was significantly associated with resistant symptoms of hypothyroidism and may be used as a marker for treatment efficacy with TSH rather than TSH value alone.

Real-world derived weight-based levothyroxine doses to achieve optimal thyrotropin target in different degrees of autoimmune hypothyroidism

Abstract Purpose All patients with overt and severe subclinical hypothyroidism (SCH), and some with mild SCH require levothyroxine (L-T4) therapy. The present study aims to report real-world derived weight-based L-T4 doses to achieve optimal–low normal–thyrotropin target in different degrees of autoimmune hypothyroidism. Methods This was a retrospective study of patients with autoimmune hypothyroidism. Inclusion criteria were consistent achievement of optimal TSH target (0.3 to 2.5 µIU/L) using a stable L-T4 dose for at least 6 months. Patients were classified into 4 groups: group 1; mild SCH, group 2; severe SCH, group 3; overt hypothyroidism, and group 4; hypothyroidism with unknown initial TSH and free T4. Weight-based L-T4 doses were calculated for each group. Results Eighty-seven, 95, 75, and 91 patients met the inclusion criteria for groups 1–4, respectively. Weight-based L-T4 dose was the lowest in group 1 (1 ± 0.25 µg/kg/day), was the highest in group 3 (1.4 ± 0.29 µg/kg/day), while in groups 2 (1.2 ± 0.26 µg/kg/day), and 4 (1.2 ± 0.31 µg/kg/day) were not statistically different from each other. There was a significant decrease in weight-based L-T4 dose with increasing body weight categories in groups 1 and 2, and a significant difference between those less than 60 or ≥ 60 years of age in group 3. Conclusion Real-world derived weight-based L-T4 doses to achieve optimal TSH target are 1, 1.2, and 1.4 µg/kg/day for patients with mild, severe SCH, and overt autoimmune hypothyroidism, respectively. Age and body weight subcategories can better fine-tune required doses.

Impending thyroid storm caused by hydatidiform mole

Introduction: Thyroid storm is a rare but life-threatening endocrine emergency. It is an acute exaggerated clinical manifestation of thyrotoxic state. We report an impending thyroid storm caused by a hydatidiform mole in a 14-year-old girl. This paper intends to describe hyperthyroidism secondary to molar pregnancy highlighting the rare but essential evaluation of hyperthyroidism. Case: A 14-year-old girl was consulted by the obstetric division to evaluate and manage hydatidiform mole with suspected hyperthyroidism. She had frequent palpitations and tremors for 1 week ago. She also complained of nausea and vomiting 1 week before admission to the hospital. We found a Burch-Wartofsky score of 25, which was categorized as an impending thyroid storm. Laboratory results showed mild anemia, low thyroid stimulating hormone (TSH) levels, high free thyroxine (T4) levels, and markedly elevated beta-human chorionic gonadotropin (beta-hCG) levels, normal Thyroid-stimulating hormone receptor antibodies (TRAb). Other laboratory parameters are mediocre. The ECG results showed sinus tachycardia. A mole tissue biopsy of the uterus confirms the morphology of the hydatidiform mole. These findings established the diagnosis of Impending Thyroid Storm caused by a hydatidiform mole. Conclusion: A hydatidiform mole can cause thyroid storm because the hormone hCG has similar structure to TSH. Doctors should always estimate the possibility of hyperthyroidism in a molar pregnancy.

Thyroid function and polycystic ovary syndrome: a Mendelian randomization study.

Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted. Single nucleotide polymorphisms (SNPs) involved in this study were acquired from The ThyroidOmics Consortium and the IEU Open Genome-wide association study (GWAS) database, respectively. In forward MR analysis, we included normal free thyroxine (FT4, n=49,269), normal thyroid-stimulating hormone (TSH, n=54,288), hypothyroidism (n=53,423) and hyperthyroidism (n=51,823) as exposure. The outcome was defined as PCOS in a sample size of 16,380,318 individuals. The exposure in the reverse MR analyses was chosen as PCOS, while the outcome consisted of the four phenotypes of thyroid function. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses. The occurrence of PCOS was associated with increased risk of hyperthyroidism (IVW, OR=1.08, 95%CI=1.02-1.13, P=0.004). No evidence suggested that other phenotypes of thyroid function were related to PCOS. Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.