Effect Of Levothyroxine Replacement Therapy Research Articles

Effects of levothyroxine replacement therapy on insulin resistance in patients with untreated primary hypothyroidism

ObjectivesThis study investigated the effects of levothyroxine replacement therapy on insulin resistance, lipid profile, and thyroid function in patients with untreated primary hypothyroidism. 105 patients with hypothyroidism with indication for levothyroxine replacement were enrolled in the present study. Insulin, fasting blood glucose and lipid profile were assessed at the beginning of diagnosis and three months after levothyroxine replacement. Insulin resistance was calculated by hemostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI).ResultsOur data revealed a significant reduction in body mass index (27.18 ± 4.27 versus 26.81 ± 4.18 kg/m2, p = 0.028), cholesterol (199.79 ± 37.61 versus 178.10 ± 32.25 mg/dl, p < 0.001), triglyceride (160.41 ± 71.86 versus 146 ± 61.11 mg/dl, p = 0.012), low density lipoprotein-cholesterol (123.54 ± 30.7 versus 107.08 ± 26.98 mg/dl, p < 0.001), fasting insulin (8.91 ± 3.92 versus 8.05 ± 2.65 mIU/l, p < 0.001), and thyroid stimulating hormone (47.47 ± 3.4 versus 2.22 ± 1.84 µIU/ml, p < 0.001) levels before and after drug intervention. However, no statistical differences were observed in HOMA-IR, QUICKI, and high density lipoprotein-cholesterol. In conclusion, in patients with untreated primary hypothyroidism, levothyroxine replacement therapy based on HOMA-IR and QUICKI did not improve insulin resistance; however, lipid profile was significantly improved following levothyroxine administration.Trial registrationThis study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20130610013612N10 on the date 2019-09-02.

The pleiotropic effects of levothyroxine replacement therapy in patients with subclinical hypothyroidism and hypertension

Background. According to epidemiological studies, the prevalence of subclinical hypothyroidism is about 6 % and it depends on age, gender, region of residence and, at the same time, significantly exceeds the frequency of primary hypothyroidism. Within one year, 5 % of cases of subclinical hypothyroidism turn into the manifested form. Delayed diagnosis of the disease increases the risk of serious complications. It is still controversial whether subclinical hypothyroidism affects blood pressure because of conflicting results in published studies. Thus, the aim of this study was to assess the effects of levothyroxine replacement therapy in patients with subclinical hypothyroidism and hypertension on lipid metabolism, functional state of the endothelium and cognition. Materials and methods. Thirty-one patients with subclinical hypothyroidism and stage 2 hypertension participa­ted in the study, among them 12 (38.71 %) men and 19 (61.29 %) women. The average age of participants was 63.19 ± 1.93 years. The study examined lipid profile, functional state of the endothelium, and cognitive functions based on the results of the Montreal Cognitive Assessment before and after 3 months of additional administration of the levothyroxine replacement thera­py at a dose 25–50 µg daily. Results. The lipid analysis revealed a significant decrease in total cholesterol for 10.08 % (5.54 ± 0.17 mmol/L against 6.23 ± 0.25 mmol/L, Р &lt; 0.05), low-density lipoprotein choleste­rol for 24.5 % (3.39 ± 0.17 mmol/L against 4.49 ± 0.27 mmol/L, Р &lt; 0.01), triglycerides for 19.42 % (1.66 ± 0.11 mmol/L against 2.06 ± 0.16 mmol/L, Р &lt; 0.05) compared to those at baseline. At the same time, patients with subclinical hypothyroidism and hypertension showed a reliable decrease in atherogenic dyslipidemias, 64.52 against 74.19 %. We also observed a reliable improvement of the functional state of the endothelium: the mean value of the endothelium-dependent vasodilation of the brachial artery increased for 11 % (6.56 ± 0.10 % against 5.91 ± 0.05 %, Р &lt; 0.001). The results of the neuropsychological testing showed a reliable improvement of the cognitive functions among examined patients: the average score on the Montreal Cognitive Assessment raised from 23.77 ± 0.60 at baseline to 26.65 ± 0.47 after three months of taking levothyro­xine, Р &lt; 0.001. Conclusions. Levothyroxine replacement therapy in patients with subclinical hypothyroidism and hypertension was followed by a normalization of lipid profile and a decrease in atherogenic dyslipidemias, an improvement of the functional state of the endothelium and state of cognition.

Short-term electrocardiographic and echocardiographic effects of levothyroxine replacement in adults with newly diagnosed hypothyroidism

Background and Aims: Thyroid hormones play a key role in modulating the cardiac function and structure. Expectedly, thyroid hormone deficiency in primary hypothyroidism has a profound and clinically relevant effect on the cardiac structure and function manifesting in characteristic electrocardiographic and echocardiographic (ECHO) abnormalities. The aim is to evaluate the effects of levothyroxine replacement therapy on the electrocardiographic (ECG) and ECHO changes in patients with primary hypothyroidism by assessing the changes in ECG and ECHO before and after 6 weeks of optimal levothyroxine (LT4) treatment in adults with newly diagnosed primary hypothyroidism. Methodology: Prospective, observational study conducted in the department of medicine in an armed forces tertiary care teaching hospital from October 2018 to April 2021. We studied newly diagnosed adults with primary hypothyroidism who were treated with optimal LT4 replacement. Descriptive statistics along with Student's t-test and Chi-square test were used to determine the statistical significance. Results: In 152 participants, the mean age was 41.0 ± 13.2 years and 79% were female. After 6 weeks of LT4 treatment, the proportion of participants with abnormal ECG findings reduced significantly (from 77% to 14.5%, P < 0.0001) with a significant reduction in those having sinus bradycardia (P < 0.0001) and low-voltage complexes (P < 0.0001). On ECHO, there was a significant improvement in left ventricular ejection fraction (P < 0.001), fractional shortening (P < 0.001), and a significant reduction in myocardial thickness parameters. The systolic and diastolic function improved significantly after 6 weeks of treatment. The proportion of patients without pericardial effusion increased from 34.9% to 79.6%. Conclusion: Replacement therapy with LT4 in newly diagnosed primary hypothyroid patients substantially improves cardiac structure, systolic and diastolic function and has a positive impact on underlying pericardial effusion. A large, prospective, trial is necessary to determine the long-term effects after thyroid hormone replacement.

Association between levothyroxine replacement therapy and osteoporosis in Riyadh, Saudi Arabia: a matched case-control study.

Hypothyroidism is a common health problem among elder women. However, conflicting results were observed regarding the association between levothyroxine treatment and osteoporosis risk. Therefore, the current study aimed to evaluate the effect of levothyroxine replacement therapy on osteoporosis risk in the Saudi population. This study was a matched case-control study conducted from June to August 2020. Data were extracted from the electronic medical records and included sociodemographic, clinical characteristics, comorbid conditions, levothyroxine replacement therapy dose, duration, concomitant therapy, and bone mineral density. Cases were matched with controls (1:1 basis) by age; the study included 256 cases and 256 controls. In the multivariate conditional logistic regression analysis, thyroxine use was independently associated with an increased likelihood of osteoporosis. Therefore levothyroxine use in elderly females was associated with an increased risk of osteoporosis, and hence, clinicians must be aware of the levothyroxine replacement therapy outcomes in postmenopausal females at risk of osteoporosis.

Effect of levothyroxine replacement therapy on testosterone, LH, FSH levels in men with overt hypothyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Calculation of left ventricular volumes and systolic indices in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) is defined as high thyroid-stimulating hormone (TSH) and normal thyroxine (T4) levels. Data on the effects of early substitution with levothyroxine on psychophysical health in SCH are not consistent enough to support its general administration. The aim of this study was to examine the effect of 3-months levothyroxine (LT4) treatment on cardiovascular function in symptomatic SCH with TSH <10mIU/L. Anthropometric, biochemical, electro- and echocardiographic indices were measured in 35 patients with persistent symptomatic SCH (4mIU/L < TSH <10mIU/L; mean±SD: 7.0±2.1mIU/L) and 40healthy controls at baseline and three months after the euthyroid state had been achieved on LT4 for SCH group, or 3months of follow-up for controls. The analyses showed a significant reduction in body weight (P=.030), systolic and diastolic blood pressure (P=.024, P=.019), TSH (P<.001) and thyroid peroxidase antibodies (TPOAb) (P<.001) on LT4 in the SCH group. There was a statistically significant decrease in end-systolic (ESV) and end-diastolic volumes (EDV) (P<.001, P<.001, respectively) after LT4 treatment. LT4 therapy significantly increased values of ejection fraction (EF), global longitudinal, circumferential and radial strains (P<.001, P<.001, P<.001, respectively). Our study confirmed an echocardiographic improvement of cardiac structure and function in treated individuals. Findings suggest the role of electrocardiographic and echocardiographic examination in objective monitoring for LT4 therapeutic effects.

Hypothyroidism and Non-alcoholic Fatty Liver Disease: Association and Effect of Levothyroxine Replacement Therapy

Background: The association between hypothyroidism and non-alcoholic fatty liver disease (NAFLD) is increasingly studied with controversial results, and evidences regarding the effect of levothyroxine replacement therapy on NAFLD are lacking. Objectives: to examine the association between overt hypothyroidism and NAFLD, and to test the effect of levothyroxine (LT4) replacement therapy on NAFLD among subjects with overt hypothyroidism. Methods: 325 recently diagnosed overt hypothyroidism subjects were compared to 325 age, sex, and BMI matched subjects regarding metabolic characteristics, serum liver enzymes, and ultrasound diagnosed NAFLD. The same comparison was performed on subjects with NAFLD in the case group before and after 12 months of LT4 replacement therapy. Results: The mean age of participants was 45.22±5.04 years old, and 369 (56.8) were females. Subjects with overt hypothyroidism had a significantly higher prevalence of NAFLD [146 (44.9) versus 83 (25.5), p < 0.001], and higher means of metabolic variables, liver enzymes, and ultrasound liver measurements (p < 0.5). At 12 months of LT4 therapy, there was 35.6% reduction in the prevalence of NAFLD (p < 0.001), and significantly reduced values of metabolic variables, and serum liver enzymes (p < 0.05) among subjects with NAFLD in the case group. Conclusions: Overt hypothyroidism was significantly associated with NAFLD. Moreover, 12 months LT4 replacement therapy significantly reduced the prevalence of NAFLD.

Meta-analytic evidence for increased low-grade systemic inflammation and oxidative stress in hypothyroid patients. Can levothyroxine replacement therapy mitigate the burden?

This series of meta-analyses were aimed to elucidate the impact of hypothyroidism on low-grade systemic inflammation and oxidative stress assessed by C-reactive protein (CRP) and malondialdehyde (MDA) respectively; and to evaluate the effect of levothyroxine replacement therapy (LRT) on those outcomes. PubMed database and the key studies references were searched prior to March 3, 2020. Data on serum or plasma CRP and MDA levels in SHT (subclinical) and/or OHT (overt) hypothyroid patients and controls were extracted to compute overall standardized mean differences (SMD) by the random-effects model. A total of 93 studies were entered into analyses and ten main meta-analyses were performed. OHT (SMD = 0.72 [0.39; 1.04], k = 35), SHT (SMD = 1.58 [0.78; 2.38], k = 56) and even mild SHT (TSH < 10 mU/L, SMD = 2.19 [0.02; 4.37], k = 13) proved to have a detrimental effect on CRP levels. LRT showed a favorable effect on CRP levels, particularly in OHT (SMD = -0.30 [-0.57; -0.02], k = 17). Increased levels of MDA were also found, especially in OHT (SMD = 2.49 [0.66; 4.31], k = 13). LRT may also improve MDA levels; however future studies would further validate the advantageous effect of LRT in hypothyroidism. Heterogeneity primarily originated from different study designs and geographic locations. Overall, these meta-analyses reveal that screening for hs-CRP and MDA in hypothyroid patients as simple biomarkers of low-grade systemic inflammation and oxidative stress may become a useful tool to identify those at increased risk who may benefit most from early interventions.

The role of echocardiography in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism

Paper description: • Clarification of the effects of levothyroxine treatment on cardiovascular risk present in subclinical hypothyroidism may contribute to the strategy in planning cardiovascular preventive treatments. • We examined whether treatment of subclinical hypothyroidism by levothyroxine has any effect on cardiac morphology and function estimated by standard electrocardiographic and echocardiographic indicators. • Our results suggest a subtle improvement of cardiac structure and function. • The study supports electrocardiographic and echocardiographic evaluation for monitoring the therapeutic effect of levothyroxine. This could also be an objective approach when deciding whether a patient should be treated permanently after the trial period. Abstract: Current controversies related to the treatment of subclinical hypothyroidism (SCH) with thyrotropin (TSH) < than 10 mU/L are based on the lack of evidence that levothyroxine therapy has beneficial effects. The aim of our study is to estimate the effect of levothyroxine treatment on cardiac morphology and function in subclinical hypothyroidism. Body mass index, waist circumference, blood pressure, electrocardiographic and standard echocardiographic parameters were measured before levothyroxine therapy and 3 months after TSH normalization. Significant reduction in systolic and diastolic blood pressure, PR, QT and QT corrected intervals, as well as increase in heart rate were recorded in the group on levothyroxine therapy. The following parameters of the left and right ventricle were significantly decreased in the treatment group: left ventricular mass index and volume, systolic and diastolic time intervals, and mitral annular plane systolic excursion (MAPSE). The increase was recorded as fractional shortening and pressure rise in early systole (dP/dt), right atrial wall thickness and diameters. Our study did not confirm differences in basic echocardiographic parameters between the treated and control groups, apart from an echocardiographic improvement of cardiac structure and function in treated individuals. The findings suggest electrocardiographic and echocardiographic screening in monitoring the therapeutic effect. https://doi.org/10.2298/ABS191029007P Received: October 29, 2019; Revised: January 5, 2020; Accepted: February 11, 2020; Published online: February 19, 2020 How to cite this article: Pandrc MS, Ristic A, Kostovski V, Milin-Lazovic J, Milic N, Ciric J. The role of echocardiography in monitoring the therapeutic effect of levothyroxine replacement therapy in subclinical hypothyroidism. Arch Biol Sci. 2020;72(1):137-46.

Levothyroxine improves Paraoxonase (PON-1) serum levels in patients with primary hypothyroidism: Case–control study

Primary hypothyroidism is associated with oxidative stress and insufficient antioxidant capacity. This study was conducted to evaluate the effects of levothyroxine replacement therapy on paraoxonase 1 (PON-1) serum levels in a patients with primary hypothyroidism. Thirty-one patients with primary hypothyroidism compared to 20 healthy controls were recruited from. A venous blood sample were taken after an overnight fasting for biochemical parameters, before and after starting levothyroxine therapy (100 μ g/day) for 3 months duration. The biochemical variables were PON-1 serum levels, lipid profiles, triiodothyronine (T3), thyroxin (T4), and thyroid stimulating hormone (TSH) serum levels. Levothyroxine replacement therapy leads to a significant amelioration of thyroid functions, lipid profile, cardiometabolic measures P < 0.05 in patients with primary hypothyroidism. Levothyroxine leads to significant elevation in PON-1 serum levels from 188.42 ± 19.81 (U/mL) to 361.23 ± 33.62 (U/mL) P < 0.0001. This study concluded that levothyroxine replacement therapy significantly increases PON-1 serum levels in patients with primary hypothyroidism and attenuating hypothyroidism-induced oxidative stress.

Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis

The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear. The aims of this study were to assess (i) the impact of SCH during pregnancy on maternal and neonatal outcomes, and (ii) the effect of levothyroxine replacement therapy in these patients. Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, the Cochrane Controlled Trials Register, Ovid EMBASE, Web of Science, and Scopus were searched from inception to January 2015. Randomized trials and cohort studies of pregnant women with SCH that examined adverse pregnancy and neonatal outcomes were included. Reviewers extracted data and assessed methodological quality in duplicate. Eighteen cohort studies at low-to-moderate risk of bias were included. Compared with euthyroid pregnant women, pregnant women with SCH were at higher risk for pregnancy loss (relative risk [RR] 2.01 [confidence interval (CI) 1.66-2.44]), placental abruption (RR 2.14 [CI 1.23-3.70]), premature rupture of membranes (RR 1.43 [CI 1.04-1.95]), and neonatal death (RR 2.58 [CI 1.41-4.73]). One study at high risk of bias compared pregnant women with SCH who received levothyroxine to those who did not and found no significant decrease in the rate of pregnancy loss, preterm delivery, gestational hypertension, low birth weight, or low Apgar score. SCH during pregnancy is associated with multiple adverse maternal and neonatal outcomes. The value of levothyroxine therapy in preventing these adverse outcomes remains uncertain.

The effect of levothyroxine replacement therapy on lipid profile and oxidative stress parameters in patients with subclinical hypothyroid

The purpose of this present study is to investigate the levels of oxidative stress parameters in patients with subclinical hypothyroidism (SH) and the effects of levothyroxine (LT4) replacement therapy on these parameters and lipid profile. At the beginning of the study blood samples were collected from the patients in order to analyse oxidative stress parameters, lipid profile and biochemical markers. After replacement therapy with LT4, in the third month, same tests were performed again. At the baseline superoxide dismutase (SOD) levels were found to be higher in SH patients, compared to the euthyroid group. After LT4 therapy, statistically significant decreases in SOD and catalase levels and increase in HDL-C levels were noticed. LT4 treatment was found to have positive effects on oxidative stress indicators and HDL-C levels.

Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism

Hypothyroidism has a variety of adverse effects on cognitive function. The treatment of levothyroxine alone cannot restore cognitive defects of hypothyroid patients. Antioxidant vitamin E supplementation could be useful in disturbances which are associated with oxidative stress and could effectively slow the progression of Alzheimer disease. Thus, the purpose of this study was to evaluate oxidative stress status of the serum and hippocampus in hypothyroidism and to examine the effects of levothyroxine replacement therapy with vitamin E supplementation on cognitive deficit. Sprague-Dawley rats were randomly divided into five groups: control group, PTU group, PTU+Vit E group, PTU+L-T4 group, and PTU+L-T4+Vit E group. Serum and hippocampus malondialdehyde (MDA) levels were determined using the thiobarbituric-acid reactive substances method. Serum and hippocampus superoxide dismutase (SOD) levels were determined by measuring its ability to inhibit the photoreduction of nitroblue tetrazolium. Learning and memory was assessed by Morris water maze test. In the present study, we found that the rats of PTU+Vit E group spent less time to find the platform on days 2, 3, 4, and 5 than the PTU group. Moreover, the rats of PTU+L-T4+Vit E group spent less time to find the platform on days 4 and 5 than the PTU+L-T4 group. The time spent in the target quadrants was measured in the probe test and no difference was observed in all groups. Oxidative damage has been observed in the serum and hippocampus of hypothyroidism rat. SOD levels of serum and hippocampus tissue were significantly increased and MDA levels were significantly decreased in the PTU+Vit E and PTU+L-T4+Vit E groups than the PTU and PTU+L-T4 groups. Therefore, these findings indicate that levothyroxine replacement therapy with vitamin E supplementation may ameliorate cognitive deficit in PTU-induced hypothyroidism through the decrease of oxidative stress status.

Effect of levothyroxine replacement therapy on coagulation and fibrinolysis in severe hypothyroidism

We previously demonstrated that patients suffering from moderate hypothyroidism were at increased risk of thrombosis contrasting with the bleeding tendency of those presenting severe hypothyroidism. The latter state is associated with hemostatic anomalies including von Willebrand type 1 disease and increased fibrinolytic capacity. With the exception of von Willebrand type 1 disease, reversibility of hemostatic changes is not established after levothyroxine replacement therapy. Therefore our objective was to analyze the reversibility of these anomalies. We analyzed the impact of levothyroxine treatment on lipid parameters, fibrinogen, platelet count, D-dimers, alpha2 antiplasmin activity, plasminogen activity, tissue plasminogen activator antigen (t-PA Ag), plasminogen activator inhibitor type 1 antigen (PAI-1 Ag) and coagulation factors (factor VIII coagulant, von Willebrand factor antigen, von Willebrand factor and factor IX) in 23 patients with severe hypothyroidism (TSH level > 50 mU/ I). Mean fibrinogen levels increased by 14.2% while t-PA Ag and PAI-1 Ag increased by 42.6 and 69%, respectively, after correction of hypothyroidism. Interestingly, post-treatment PAI-1 Ag levels tended to be higher in patients with normal-high final TSH levels than in patients with normal-low final TSH levels. Our results suggest that normalization of fibrinolysis is obtained after a transient decrease of fibrinolytic activity. We also confirmed the correction of coagulation factor abnormalities upon levothyroxine replacement therapy. We demonstrated that the coagulation disorders and the hyperfibrinolytic status of severe hypothyroid patients were corrected upon levothyroxine therapy. However, the clinical consequences of the transient decrease of the fibrinolytic activity during the course of TSH normalization need further studies.