Elevated Serum Thyroid-stimulating Hormone Levels Research Articles

Thyroid disease-related sleep disorders and its diagnostic and therapeutic recommendations: A literature review

As perioperative medicine evolves, more hospitals are offering comfort sleep clinics. Thyroid disorders (e.g., hypothyroidism, hyperthyroidism, and thyroid cancer) affect the peripheral circadian clock. Elevated serum thyroid-stimulating hormone levels have been found to associate with the incidence of thyroid cancer in humans, but the relationship between circadian disruption and thyroid disease requires further investigation. Malignant transformation of thyroid nodules is characterized by disruption of the expression of biological clock genes. Sleep clinics often see patients complaining of sleepiness and tinnitus. These patients often have comorbid thyroid disorders and are therefore highly susceptible to misdiagnosis or underdiagnosis. In this article, we first summarize this category of disorders, which we propose to classify as insomnia secondary to somatic disease and define as thyroid disease-related sleep disorder (TSD). The primary and common clinical complaints of TSD patients are different types of sleep disorders. In addition, we attempt to provide some preliminary diagnostic and therapeutic recommendations for TSD in the hope that it may assist healthcare professionals in the early diagnosis and management of this disorder.

The negative impact of levothyroxine treatment on urinary luteinizing hormone measurements in pediatric patients with thyroid disease.

Previous studies suggest urinary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements by immunofluorometric assays (IFMA) as noninvasive alternatives to serum assays for puberty assessment. However, these studies excluded patients with other endocrine disorders and those taking medications. Besides, the recent discontinuation of IFMA manufacturing is a concern. We explored the utility of luminometric assays (LIA) for urinary gonadotropins and thyroid-stimulating hormone (TSH) determinations in euthyroid patients with thyroid pathologies. We used LIA and IFMA assays to measure serum and first-morning-voided (FMV) urine LH, FSH, and TSH concentrations in euthyroid patients with various thyroid disorders. Of the 47 euthyroid patients with normal serum TSH (S-TSH) levels, 14 were receiving levothyroxine therapy. FMV total urinary LH (U-LH) concentrations correlated significantly with those measured in serum using either LIA (r=0.67, P<.001) or IFMA (r=0.83, P=.003) in patients not receiving levothyroxine treatment; however, no significant correlation could be detected in patients receiving levothyroxine regardless of the assay method (for LIA: r=0.50, P=.08 and IFMA r=0.44, P=.15). Urinary TSH (U-TSH) concentrations correlated poorly with those in serum in both the untreated and the treated groups (r=-0.13, P=.49, and r=-0.45, P=.11, respectively). FMV total U-LH determinations by LIA can be used to assess pubertal development in patients with thyroid pathology, provided the euthyroid patient is not on levothyroxine treatment. U-TSH measurements by LIA cannot replace invasive S-TSH measurements at least in patients with normal S-TSH levels. Further research may reveal the utility of U-TSH determinations in patients with elevated S-TSH levels.

Development of a predictive score for post-hemithyroidectomy hypothyroidism using skeletal muscle index, remnant thyroid index, and thyroid-stimulating hormone levels: a retrospective cohort study.

Hypothyroidism is a major complication of hemithyroidectomy. Low remnant thyroid volume and high serum thyroid-stimulating hormone (TSH) levels are suggested as risk factors for post-hemithyroidectomy hypothyroidism. Reduced skeletal muscle mass is associated with a variety of postoperative complications. However, its impact on post-hemithyroidectomy hypothyroidism has not yet been studied. This study aimed to evaluate the association between skeletal muscle mass and the onset of post-hemithyroidectomy hypothyroidism and develop a predictive score using skeletal muscle mass in combination with previously reported risk factors. This study retrospectively analyzed 226 consecutive patients who underwent hemithyroidectomy at Shinshu University Hospital between January 2011 and December 2020. The skeletal muscle area at the fourth thoracic vertebral level and maximal remnant thyroid area were quantified using preoperative computed tomography and standardized by dividing them by the square of the patient's height, designated as the skeletal muscle index (SMI) and remnant thyroid volume index (RTI). Subclinical hypothyroidism was defined as a postoperative elevated serum TSH level (>5 µU/mL) with a normal free thyroxine (FT4) level (≥0.9 ng/dL), overt hypothyroidism as a postoperative increase in serum TSH level (>5 µU/mL) and a decrease in serum FT4 level (<0.9 ng/dL), and symptomatic hypothyroidism as an elevated serum TSH level (>5 µU/mL) with hypothyroidism-related symptoms. Logistic regression analysis was used to determine the factors associated with the onset of hypothyroidism. Patients with euthyroid status had significantly higher SMI and RTI than those who developed post-hemithyroidectomy hypothyroidism (SMI, euthyroid: 12.0±2.4 vs. subclinical hypothyroid: 10.2±1.7, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 10.1±1.7, P<0.001, RTI, euthyroid: 1.19±0.41 vs. subclinical hypothyroid: 0.92±0.35, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 0.84±0.30, P<0.001). Multivariable analysis demonstrated that low SMI, low RTI [hazard ratio (HR): 3.35, P<0.001], and preoperative high serum TSH levels (HR: 2.54, P=0.003) were independent predictive factors for hypothyroidism. Patients who had low SMI, low RTI, and preoperative high serum TSH levels were more likely to develop hypothyroidism (68.8%) than those with either one (25.3%), two (47.8%), or none (15.2%) of these three factors. Preoperative evaluation of the SMI, RTI, and serum TSH levels may be useful in predicting the development of post-hemithyroidectomy hypothyroidism.

The Correlation between the First Trimester Combined Test Results and Thyroid Stimulating Hormone Levels as Well as Its Effect on Pregnancy Outcomes.

Determining the pregnancy outcomes with independent prognostic factors in the first trimester combined screening test and thyroid stimulating hormone (TSH) is a concern for practitioners. We aimed to evaluate the correlation between TSH and first trimester combined screening test levels and examine their effects on pregnancy outcomes in healthy pregnant women. A total of 349 pregnant women in Izmir Ataturk Training and Research Hospital, Turkey with normal TSH values in the first trimester between 2015 and 2020 were enrolled. Patients were divided into two groups as 274 and 75 patients according to TSH values with 2,5 as cut-off value; their birth weights and weeks were compared. Patients were also divided into three groups according to gestational weeks; their TSH values and combined tests were compared. When grouped based on the TSH threshold value (2.5uIU/ml), no significant relationship was found between the combined test parameters and TSH levels. In the combined test, after grouping according to the week of gestation, a negative correlation was observed between free beta-human chorionic gonadotropin (β-hCG) and TSH measured at 11 weeks (P=0.040, r=-0.189). A significant negative correlation was found between free β-hCG and newborn birth weight (P=0.032, r=-0.199), TSH and delivery time (P=0.011, r=-0.235). Free β-hCG and TSH levels could guide practitioners for birth weight and early delivery, respectively. Postponing the combined test for patients with elevated serum TSH levels to between the 12th and 13th weeks of gestation may reduce false positives.

Benefits of rescreening newborns of mothers affected by autoimmune hypothyroidism.

IntroductionInfants of mothers with autoimmune hypothyroidism (AH) are at risk of developing late-onset hypothyroidism, often escaping at newborn screening. This condition might be caused both by the action of maternal antibodies and/or by maternal treatment.ObjectivesThe aim of this study is to evaluate the prevalence of AH in the mothers of children born in Veneto region, Italy, and to define what is the most appropriate management for these newborns.MethodsNewborns of six different hospitals with a mother suffering from AH and with negative neonatal screening for congenital hypothyroidism (CH) were included in the study. Between 15 and 20 days of life, we collected a serum sample for the evaluation of thyroid function (thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3)) and anti-thyroid antibodies. On the same occasion, a capillary blood sampling was performed for a second screening test.ResultsMaternal AH has a prevalence of 3.5%. A total of 291 newborns were enrolled from November 2019 to May 2021. Whereas the 11.4% of infants had a slight elevated serum TSH (>6 mU/L) and required a follow-up, only 2 children presented an elevated TSH level at the second screening test. One of these, with the gland in situ, showed persistently elevated serum TSH levels and required treatment with levothyroxine.ConclusionsMaternal AH rarely caused neonatal thyroid dysfunction. We suggest to reassess newborns from mothers with AH 15 days after birth by means of a second neonatal screening test. This procedure avoids false negatives due to maternal thyroid status, is less invasive and cheaper than the serum TSH evaluation, and prevents a long follow-up.

Risk factors for thyroid hormone replacement therapy after hemithyroidectomy and development of a predictive nomogram

PurposeHemithyroidectomy is a valid operation to retain functional contralateral thyroid lobe that is indicated for a variety of thyroid diseases. This study aimed at determination of the risk factors for thyroid hormone replacement following hemithyroidectomy and to develop a predictive nomogram.MethodsData of patients treated by hemithyroidectomy for benign thyroid disease between January 2015 and January 2020 were retrospectively analyzed. Baseline characteristics, surgery-related variables, and preoperative and postoperative thyroid function of patients were collected from the case records and compared between patients with postoperative euthyroidism and patients with postoperative hypothyroidism. Postoperative euthyroidism patients without thyroid hormone replacement were compared to those who developed postoperative hypothyroidism with thyroid hormone replacement. The factors associated with thyroid hormone replacement were used to construct a binomial logistic-regression model and visualized as a predictive nomogram to evaluate the risk of thyroid hormone replacement following hemithyroidectomy.ResultsOf the 378 patients (74% female) included in the study, 110 (29.1%) developed postoperative hypothyroidism. Preoperative serum thyroid-stimulating hormone (TSH) > 2.172 μIU/mL was identified as an independent risk factor for postoperative hypothyroidism (odds ratio [OR] = 8.02; 95% confidence interval [CI]: 4.87–13.20; P < 0.001). Of 110 patients with postoperative hypothyroidism, 56 (50.9%) received thyroid hormone replacement. Unilateral thyroid nodule and preoperative serum TSH > 2.172 μIU/mL were independent predictors of postoperative thyroid hormone replacement (P = 0.01, and P < 0.001, respectively). Temporary subclinical hypothyroidism occurred in 12 patients; all 12 reverted to euthyroid state without thyroid hormone replacement. The discriminative effect of the binomial regression model was proved reliable by the Hosmer–Lemeshow goodness-of-fit test (P = 0.503), and predictive ability of the nomogram was satisfactory with a C-index of 0.833.ConclusionsHypothyroidism is common after hemithyroidectomy, and almost half of the patients will need thyroid hormone replacement. Elevated preoperative serum TSH level and unilateral thyroid nodule were independent predictors of thyroid hormone replacement following hemithyroidectomy. The predictive nomogram could be a useful tool for clinical practice.

Elevated serum thyrotropin levels and endothelial dysfunction in a prospective hemodialysis cohort.

Thyroid dysfunction is a highly prevalent yet under-recognized complication in hemodialysis patients. In the general population, hypothyroidism has been associated with endothelial dysfunction due to impaired vasodilator synthesis and activity. Little is known about the association of serum thyrotropin (TSH), the most sensitive and specific single biochemical metric of thyroid function, with endothelial function in hemodialysis patients. In a secondary analysis of 99 patients from the Anti-inflammatory and anti-oxidative nutrition in hypoalbuminemic dialysis patients (AIONID) trial, we examined measurements of serum TSH and endothelial function ascertained by fingertip digital thermal monitoring (DTM), a novel method used to measure micro-vascular reactivity, collected within a 90-day period. DTM was used to measure changes in fingertip temperature during and after an ischemic stimulus (blood pressure cuff occlusion) as an indicator of changes in blood flow, and two DTM indices were assessed, namely adjusted (a) Temperature Rebound (TR), defined as the maximum temperature rebound post-cuff deflation, and adjusted (b) Area Under the Temperature Curve (TMP-AUC), defined as area under the curve between the maximum and minimum temperatures. We examined the relationship between serum TSH with impaired TR (separately) and TMP-AUC (both defined as less than the median level of observed values) using multivariable logistic regression. In unadjusted and case-mix analyses, higher serum TSH levels (defined as the three highest quartiles) were associated with lower (worse) TR (ref: lowest TSH quartile): ORs (95% CI) 2.64 (1.01-6.88) and 2.85 (1.08-7.57), respectively. In unadjusted and case-mix analyses, higher TSH levels were associated with lower (worse) TMP-AUC: ORs (95% CI) 2.64 (1.01-6.88) and 2.79 (1.06-7.38), respectively. In HD patients, higher serum TSH levels were associated with worse micro-vascular reactivity measured by DTM. Further studies are needed to determine if thyroid hormone supplementation improves endothelial function in hemodialysis patients with lower levels of thyroid function.

Thyroid Stimulating Hormone Correlation with Analysis of Fasting Bile and Stone in Gallstone Diseases

Background and Aims To correlate serum TSH (Thyroid stimulating hormone) levels with fasting bile cholesterol and TSH levels and with type of stone in gallstone disease. Materials and Methods A cross sectional study was conducted from October 2016 to August 2018 in the hospitals attached with Kasturba medical college, Mangalore. A detailed pro forma was developed to record information regarding patients hospital details, age, sex, routine blood investigations, special investigations and imaging study. Results Study conducted in 48 patients (22 male and 26 female) with diagnosed gallstone disease. A 23% of patients have elevated serum TSH who never had history of thyroid disease. Though maximum number of those with elevated TSH were in the 31-40 years category (5 out of 20), the higher proportion was seen in the 41-50 years age group (42.9%, that is; 3 out of total 7). A significant 33% of patients had elevated fasting bile TSH levels with female preponderance, even higher than the number of those with elevated serum TSH level. The number of patients with elevated bile TSH fell in the 31-40 years age group (8 out of 20), the higher proportion was seen in the 41-50 years age group (57.1%, that is, 4 out of 7). Conclusion A statistically significant independent relationship between serum TSH and fasting bile TSH were established with female patients of gallstone disease. Subclinical hypothyroidism indeed plays a significant role in cholesterol cholelithiasis, especially in women.

Levothyroxine for the Treatment of Subclinical Hypothyroidism and Cardiovascular Disease.

Subclinical hypothyroidism is a biochemical condition defined by elevated serum thyroid-stimulating hormone levels in the setting of normal levels of the peripheral thyroid hormones, thyroxine and triiodothyronine. Thyroid hormones act on the heart through various mechanisms and subclinical hypothyroidism has been associated with risk factors for cardiovascular disease, such as hypertension and dyslipidemia. In addition, evidence from multiple studies supports an association between subclinical hypothyroidism and cardiovascular disease. However, the use of levothyroxine in subclinical hypothyroidism to reduce cardiovascular disease risk is not clearly beneficial. Treatment with levothyroxine may only provide benefit in certain subgroups, such as patients who are younger or at higher risk of cardiovascular disease. At present, most of the international societal guidelines advise that treatment decisions should be individualized based on patient age, degree of serum thyroid-stimulating hormone (TSH) elevation, symptoms, cardiovascular disease (CVD) risk, and other co-morbidities. Further study in this area is recommended.

Subclinical Hypothyroidism as an Independent Determinant of Left Atrial Dysfunction in the General Population.

Although subclinical hypothyroidism (SCH) is a common clinical entity and carries independent risk for incident heart failure (HF), its possible association with subclinical cardiac dysfunction is unclear. Left ventricular global longitudinal strain (LVGLS) and left atrial (LA) phasic strain can unmask subclinical left heart abnormalities and are excellent predictors for HF. This study aimed to investigate the association between the presence of SCH and subclinical left heart dysfunction in a sample of the general population without overt cardiac disease. We examined 1078 participants who voluntarily underwent extensive cardiovascular health check-ups, including laboratory tests and 2-dimensional speckle-tracking echocardiography to assess LVGLS and LA reservoir, conduit, and pump strain. SCH was defined as an elevated serum thyroid-stimulating hormone level with normal concentration of free thyroxine. Mean age was 62 ± 12 years, and 56% were men. Seventy-eight (7.2%) participants exhibited SCH. Individuals with SCH had significantly reduced LA reservoir (37.1 ± 6.6% vs 39.1 ± 6.6%; P = 0.011) and conduit strain (17.3 ± 6.3% vs 19.3 ± 6.6%; P = 0.012) compared with those with euthyroidism, whereas there was no significant difference in left ventricular ejection fraction, LA volume index, LVGLS, and LA pump strain between the 2 groups. In multivariable analyses, SCH remained associated with impaired LA reservoir strain, independent of age, traditional cardiovascular risk factors, and pertinent laboratory and echocardiographic parameters. including LVGLS (standardized β -0.054; P = 0.032). In an unselected community-based cohort, individuals with SCH had significantly impaired LA phasic function. This association may be involved in the higher incidence of HF in subjects with SCH.

Thyroid Disorders in Homozygous β-Thalassemia: Current Knowledge, Emerging Issues and Open Problems.

Changes in thyroid function and thyroid function tests occur in patients with β-thalassemia major (TM). The frequency of hypothyroidism in TM patients ranges from 4% to 29 % in different reports. The wide variation has been attributed to several factors such as patients’ genotype, age, ethnic heterogeneity, treatment protocols of transfusions and chelation, and varying compliance to treatment. Hypothyroidism is the result of primary gland failure or insufficient thyroid gland stimulation by the hypothalamus or pituitary gland. The main laboratory parameters of thyroid function are the assessments of serum thyroid-stimulating hor-mone (TSH) and serum free thyroxine (FT4). It is of primary importance to interpret these measurements within the context of the laboratory-specific normative range for each test. An elevated serum TSH level with a standard range of serum FT4 level is consistent with subclinical hypothyroidism. A low serum FT4 level with a low, or inappropriately normal, serum TSH level is consistent with secondary hypothyroidism. Doctors caring for TM patients most commonly encounter subjects with subclinical primary hypothyroidism in the second decade of life. Several aspects remain to be elucidated as the frequency of thyroid cancer and the possible existence of a relationship between thyroid dysfunction, on one hand, cardiovascular diseases, components of metabolic syndrome (insulin resistance) and hypercoagulable state, on the other hand. Further studies are needed to explain these emerging issues. Following a brief description of thyroid hormone regulation, production and actions, this article is conceptually divided into two parts; the first reports the spectrum of thyroid disease occurring in patients with TM, and the second part focuses on the emerging issues and the open problems in TM patients with thyroid disorders.

Hypothyroidism in Clinical Practice

Hypothyroidism in Clinical Practice

Thyroid nodules: diagnosis and management.

Thyroid nodules are common. Their importance lies in the need to assess thyroid function, degree of and future risk of mass effect, and exclude thyroid cancer, which occurs in 7-15% of thyroid nodules. There are four key components to thyroid nodule assessment: clinical history and examination, serum thyroid stimulating hormone (TSH) measurement, ultrasound and, if indicated, fine-needle aspiration (FNA). If the serum TSH is suppressed, a thyroid scan with 99Tc can distinguish between a solitary hot nodule, a toxic multinodular goitre or, less commonly, thyroiditis or Graves' disease within a coexisting nodular thyroid. Scintigraphically cold nodules are evaluated in the same way as in the setting of normal or elevated serum TSH levels. Thyroid ultrasonography should be performed only for palpable goitre and thyroid nodules and by specialists with expertise in thyroid sonography. Routine thyroid cancer screening is not recommended, except in high risk individuals, as the detection of early thyroid cancer has not been shown to improve survival. FNA may be performed for nodules ≥ 1.0 cm depending on clinical and sonographic risk factors for thyroid cancer. FNA specimens should be read by an experienced cytopathologist and be reported according to the Bethesda Classification System. Molecular analysis of indeterminate FNA samples has potential to better discriminate benign from malignant nodules and thus guide management. Surgery is indicated for FNA findings of malignancy or indeterminate cytology when there is a high risk clinical context. Surgery may also be indicated for suspicion of malignancy; larger nodules, especially with symptoms of mass effect; and in some patients with thyrotoxicosis.

Blocking mitochondrial cyclophilin D ameliorates TSH-impaired defensive barrier of artery

AimsEndothelial cells (ECs) constitute the defensive barrier of vasculature, which maintains the vascular homeostasis. Mitochondrial oxidative stress (mitoOS) in ECs significantly affects the initiation and progression of vascular diseases. The higher serum thyroid stimulating hormone (TSH) level is being recognized as a nonconventional risk factor responsible for the increased risk of cardiovascular diseases in subclinical hypothyroidism (SCH). However, effects and underlying mechanisms of elevated TSH on ECs are still ambiguous. We sought to investigate whether cyclophilin D (CypD), emerging as a crucial mediator in mitoOS, regulates effects of TSH on ECs. Methods and resultsSCH patients with TSH > = 10mIU/L showed a positive correlation between serum TSH and endothelin-1 levels. When TSH levels declined to normal in these subjects after levothyroxine therapy, serum endothelin-1 levels were significantly reduced. Supplemented with exogenous thyroxine to keep normal thyroid hormones, thyroid-specific TSH receptor (TSHR)-knockout mice with injection of exogenous TSH exhibited elevated serum TSH levels, significant endothelial oxidative injuries and disturbed endothelium-dependent vasodilation. However, Tshr-/- mice resisted to TSH-impaired vasotonia. We further confirmed that elevated TSH triggered excessive mitochondrial permeability transition pore (mPTP) opening and mitochondrial oxidative damages in mouse aorta, as well as in cultured ECs. Genetic or pharmacological inhibition of CypD (the key regulator for mPTP opening) attenuated TSH-induced mitochondrial oxidative damages and further rescued endothelial functions. Finally, we confirmed that elevated TSH could activate CypD by enhancing CypD acetylation via inhibiting adenosine monophosphate-activated protein kinase/sirtuin-3 signaling pathway in ECs. ConclusionsThese findings reveal that elevated TSH triggers mitochondrial perturbations in ECs and provide insights that blocking mitochondrial CypD enhances the defensive ability of ECs under TSH exposure.

Subclinical hypothyroidism

Subclinical hypothyroidism (SCH) is defined as an elevated serum thyroid-stimulating hormone level with a normal total and free thyroxine (T4) level. There is a certain degree of debate regarding the risks associated with this condition and whether treatment is beneficial. Individuals with SCH are either asymptomatic or present with milder symptoms than those with overt hypothyroidism. Although SCH does not cause significant clinical abnormalities, there are certain long-term consequences which have been documented. The diagnosis is based purely on biochemical investigations. Treatment of this condition is not indicated in all cases since thyroid function tests tend to normalize in 6%–35% of patients. However, there are specific clinical indications for treatment and oral levothyroxine is the treatment of choice in such situations.

Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Elderly Antipsychotic-Treated Women With Type 2 Diabetes and Subclinical Hypothyroidism: A Preliminary Study.

Metformin was found to reduce elevated serum thyrotropin levels, and this effect was partially determined by endogenous dopaminergic tone. The aim of this study was to compare the effect of metformin treatment on hypothalamic-pituitary-thyroid axis activity in elderly women with subclinical hypothyroidism treated with antipsychotic agents and not receiving this drug. The study population consisted of 34 elderly women with subclinical hypothyroidism, 16 of whom received antipsychotic drugs. Because of coexistent type 2 diabetes, these women were treated with metformin (2.55-3 g daily). Glucose homeostasis markers as well as serum levels of thyrotropin, free thyroid hormones and prolactin were measured at the beginning of the study and 6 months later. Thirty women completed the study. With the exception of prolactin, baseline serum levels of the assessed hormones were comparable in both study groups. Although metformin reduced serum thyrotropin levels in both groups, this effect was more pronounced in the antipsychotic-treated than in the antipsychotic-naive patients. The effect on serum prolactin was observed only in antipsychotic-treated patients. The impact on serum thyrotropin levels correlated with improvement in insulin sensitivity and with a reduction in prolactin levels. Free thyroxine and free triiodothyronine remained at a similar level throughout the study. The obtained results indicate that metformin reduces serum thyrotropin levels in elderly women, and this effect is particularly pronounced in women with diminished dopaminergic transmission.

Sex-dependent effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with subclinical hypothyroidism

Metformin was found to reduce elevated serum thyrotropin levels. No previous study has compared the effect of this drug on serum levels of thyrotropin and thyroid hormones between men and women. The study included 23 women and 12 men with subclinical hypothyroidism, who because of coexisting diabetes or impaired fasting glucose were treated with metformin (1.7-3.0g daily). Fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, serum levels of thyrotropin, free and total thyroid hormones and prolactin, as well as thyroid peroxidase and thyroglobulin antibodies were assessed at baseline and after 4 months of metformin treatment. Baseline serum levels of thyrotropin, free thyroxine and free triiodothyronine, as well as a percentage of patients with positive thyroid peroxidase and thyroglobulin antibodies were comparable in both sexes. Metformin treatment reduced plasma glucose and insulin resistance, irrespective of the gender. However, only in women, metformin decreased serum thyrotropin levels. Neither in men nor in women, metformin affected serum levels of thyroid hormone and prolactin, as well as in the subgroups of patients with thyroiditis thyroid antibody titers. The obtained results suggest that sex may determine the effect of metformin on hypothalamic-pituitary-thyroid axis activity.

The Association of Subclinical Hypothyroidism and Pattern of Circulating Endothelial-Derived Microparticles Among Chronic Heart Failure Patients.

Background:Subclinical hypothyroidism (SH) is diagnosed biochemically by the presence of normal serum free thyroxine concentration, in conjunction with an elevated serum thyroid-stimulating hormone level. Recent studies have demonstrated the frequent association between SH and cardiovascular diseases and risk factors.Objectives:To evaluate the impact of SH on patterns of circulating endothelial-derived microparticles, (EMPs) among chronic heart failure (CHF) patientsPatients and Methods:This is a retrospective study involving a cohort of 388 patients with CHF. Fifty-three CHF subjects had SH and 335 patients were free from thyroid dysfunction. Circulating levels of N-terminal-pro brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), thyroid-stimulating hormone (TSH), total and free thyroxine (T4), and triiodothyronine (T3), and endothelial apoptotic microparticles (EMPs), were measured at baseline. SH was defined, according to contemporary clinical guidelines, as a biochemical state associated with an elevated serum TSH level of greater 10 μU/L and normal basal free T3 and T4 concentrations.Results:Circulating CD31+/annexin V+ EMPs were higher in patients with SH compared to those without SH. In contrast, activated CD62E+ EMP numbers were not significantly different between both patient cohorts. Using uni (bi) variate and multivariate age- and gender-adjusted regression analysis, we found several predictors that affected the increase of the CD31+/annexin V+ to CD62E+ ratio in the patient study population. The independent impact of TSH per 6.5 μU/L (odds ratio [OR] = 1.23, P = 0.001), SH (OR = 1.22, P = 0.001), NT-proBNP (OR = 1.19, P = 0.001), NYHA class (OR = 1.09, P = 0.001), hs-CRP per 4.50 mg/L (OR = 1.05, P = 0.001), dyslipidemia (OR = 1.06, P = 0.001), serum uric acid per 9.5 mmol/L (OR = 1.04, P = 0.022) on the increase in the CD31+/annexin V+ to CD62E+ ratio, was determined.Conclusions:We believe that the SH state in CHF patients may be associated with the impaired pattern of circulating EMPs, with the predominantly increased number of apoptotic-derived microparticles.

Sodium selenite enhances thyroid uptake of iodine-131 and regulates thyroid function in rats.

The aim of the present study was to evaluate the role of selenium (Se) on the thyroid uptake and retention of radioiodine ((131)I) and on the serum levels of thyroid hormones. Experimental rats were divided into four groups with 10 animals in each group viz: untreated controls, (131)II-treated, Se-treated and (131)I+Se-treated. Group II and Group IV animals were injected intraperitoneally with 3.7MBq of (131)I. Group III and Group IV animals received Se in the form of sodium selenite, everyday at a dose of 1ppm in drinking water. Thyroidal (131)II uptake measurements, determination of biological half life of (131)I and estimation of serum of tri-iodothyronine (T3) and tetra-iodothyronine (T4) and thyroid stimulating hormone (TSH) were carried out at two time intervals after 2 and 4 weeks. The statistical significance of the data was determined by using one-way analysis of variance (ANOVA) followed by Newman-Keuls test. The results showed lower serum levels of T3 and T4 and higher TSH levels in rats treated with (131)I when compared to untreated rats. Furthermore, the biological half life (Tbiol) of (131)I in thyroid and thyroidal (131)I uptake values at 2h and 24h were significantly lower in rats treated with (131)I compared with untrated control. Selenium treatment of (131)I treated rats resulted in a significant increase in the thyroid uptake as well as Tbiol of (131)I which indicated its increased retention. Moreover, normalization of the elevated serum TSH levels and a significant increase in the T3 and T4 levels was evident when Se was administered to the (131)I treated rats. In conclusion, this study indicates that Se when given to rats in the form of sodium selenite, at a dose of 1ppm in drinking water enhances the uptake and retention of (131)I in the thyroid as well as regulates thyroid hormone levels.

Activation of tumor cell proliferation by thyroid hormone in a mouse model of follicular thyroid carcinoma

Thyroid cancers are the most common malignancy of the endocrine system in humans. To understand the molecular genetic events underlying thyroid carcinogenesis, we have generated a mouse model that spontaneously develops follicular thyroid carcinoma similar to human thyroid cancer (Thrb(PV/PV) mouse). This mutant mouse harbors a dominant-negative mutated thyroid hormone receptor β (denoted PV). The PV mutation was identified in a patient with resistance to thyroid hormone (TH). Thrb(PV/PV) mice exhibit highly elevated serum thyroid-stimulating hormone levels and increased TH. We have previously shown that thyroid-stimulating hormone is required, but not sufficient to induce metastatic follicular thyroid cancer in Thrb(PV/PV) mice. However, whether the elevated TH also contributes to the thyroid carcinogenesis of Thrb(PV/PV) mice was not elucidated. To understand the role of TH in thyroid carcinogenesis, we blocked the production of TH by treating Thrb(PV/PV) mice with propylthiouracil (Thrb(PV/PV)-PTU mice) and compared the development of thyroid cancer in Thrb(PV/PV)-PTU and untreated Thrb(PV/PV) mice. We found that thyroid tumor growth was reduced by ∼42% in Thrb(PV/PV)-PTU mice as compared with Thrb(PV/PV) mice. Analysis by bromodeoxyuridine-nuclear labeling showed decreased incorporation of bromodeoxyuridine in thyroid tumor cells of Thrb(PV/PV)-PTU mice, indicative of decreased tumor cell proliferation. However, cleaved-caspase 3 staining showed no apparent changes in apoptosis of tumor cells in Thrb(PV/PV)-PTU mice. Molecular studies identified a marked attenuation of the PI3K-AKT-β-catenin signaling pathway that led to decreased protein levels of cyclin D2, thereby decreasing tumor cell proliferation in Thrb(PV/PV)-PTU mice. Furthermore, matrix metalloproteinase-2, a downstream target of β-catenin and a key regulator during tumor invasion and metastasis, was also decreased. Thus, the present study uncovers a critical role of TH in promoting the thyroid carcinogenesis of Thrb(PV/PV) mice via membrane signaling events. Importantly, these findings suggest that anti-thyroid drugs could be considered as possible therapeutic agents of thyroid cancer.