Normal Thyroid Hormone Levels Research Articles

Revisión de la evolución de los pacientes con hipertirotropinemia y estudio de costes

IntroductionSubclinical hypothyroidism is defined as elevation of thyroid-stimulating hormone (TSH) levels, with normal thyroid hormone levels and negative autoimmunity, in asymptomatic patients with no findings on examination. Because of the unwarranted increase in thyroid function tests in asymptomatic children, the main objective of this review was to analyze the course of these patients. Analysis of associated costs was a secondary objective. Material and methodsA longitudinal, observational, retrospective study of patients referred to the endocrinology department of a tertiary hospital for high TSH levels (TSH 5-20mIU/L). Clinical and laboratory variables, number of visits until discharge, need for treatment, monitoring time, and economic variables were collected. ResultsThe study sample consisted of 155 patients with a mean age of 7.8years ±3.6SD. Referrals to endocrinology accounted for 4% of first office visits. Baseline mean TSH level was 7.8mU/L (5.03-15.8mU/L). TSH levels normalized after the first repeated measurement during the subsequent month in 60% of cases. A total of 83.6% of patients were discharged within a maximum of 3years, with a mean follow-up of 8.14 ±6.8months and 2.4visits/patient. Average cost per patient was €251.27 (range €143.49-444.21). ConclusionIt is essential not to alarm the family when subclinical hypothyroidism is detected, because this is a biochemical situation which normalizes in most cases. This fact, together with the mean cost of specialized care, suggests that the first step should be repeated TSH measurements in primary care.

SUN-578 Severe Hyperbilirubinemia Due to Graves' Thyrotoxicosis

Introduction: Graves’ disease is the most common cause of hyperthyroidism in the United States. Though hepatic dysfunction has been described in patients with thyrotoxicosis due to Graves’ disease, it is an extremely rare cause of severe hyperbilirubinemia. There is limited evidence to guide physicians in the management of hyperthyroidism associated with liver dysfunction, making it a diagnostic and therapeutic challenge. Case Report: 30-year-old woman with no significant history presented with complaints of diarrhea and yellowish discoloration of skin for more than a month. She had generalized itching, hand tremors and a 30 lb. weight loss during this period. On physical examination, she was noted to have tachycardia, scleral icterus, a diffuse non-nodular non-tender goiter, bilateral fine tremors and hyperreflexia. Abdomen was soft and non-tender with no hepatosplenomegaly. Laboratory evaluation showed normal compete blood count, total bilirubin 26 mg/dL, direct bilirubin 17.7 mg/dL, indirect bilirubin 9.1 mg/dL, ALT 49 IU/L, AST 26 IU/L, ALP 265 IU/L. She had biochemical hyperthyroidism with TSH less than 0.01 UIU/ml (0.45-4.5), free T4 of 4 ng/dL (0.6-1.3), total T3 371 ng/dL (79-149). TSI was elevated 2.13 (0-0.55). Further work up of hyperbilirubinemia including hepatitis viral panel, anti-nuclear antibody, anti-mitochondrial and anti-smooth muscle antibodies were negative. Ultrasound of the liver showed no abnormalities. Liver biopsy revealed benign liver with bland canalicular stenosis in central zones. There were no features of autoimmune hepatitis or chronic hepatitis. She underwent I131 ablation with normalization of ALP and bilirubin levels at 3 months follow-up. Discussion: Hepatic dysfunction has been described in patients with hyperthyroidism since it was reported in 1874. It may occur because of hyperthyroidism per se, drug treatment of hyperthyroidism and conditions associated with autoimmune thyroid disease like autoimmune hepatitis and primary biliary cirrhosis. The causes could also be unrelated to hyperthyroidism like viral hepatitis, alcohol abuse, sepsis, cholangitis, medications. Several theories have been hypothesized, but the mechanism of the hepatic dysfunction due to hyperthyroidism per se is not clear. A thorough work up is essential to rule out other potential etiologies. If clinically feasible, liver biopsy may be deferred initially. However, it should be considered if liver function fails to improve despite normalization of thyroid hormone levels. I131 ablation is a safe and effective method of treatment in these patients.

OR10-5 Reduced Sensitivity to Thyroid Hormone Due to Fetal Exposure to High Thyroid Hormone Levels Is Transmitted along Male Line to Two Subsequent Generations

Exposure of human embryos to high maternal thyroid hormone (TH) concentrations not only affects the newborn but also reduces thyrotroph sensitivity to TH during adult life. Based on results in mice, this latter effect is likely due to induction of the pituitary deiodinase type 3, which accelerates TH inactivation, decreasing therefore the suppression of TSH and resulting in reduced sensitivity to TH (RSTH). As the gene encoding for deiodinase 3 has parent of origin imprinting, we wondered if the effect is transmitted to subsequent generations. We therefore studied the progeny of wild-type (WT) adults (second and third generations), descendent of grandmothers and great grandmothers with high TH levels but euthyroid due to THRB gene mutations, who gave birth to the first WT generation exposed to high TH levels during fetal life. Each subject received 200 µg of thyrotropin-releasing hormone (TRH) iv after 3 days oral treatment with 25 µg liothyronine (L-T3) given twice daily. Blood was collected at intervals over the period of 180 min and analyzed for TSH, prolactin (PRL), sex hormone-binding globulin, ferritin, cholesterol, and creatinine kinase. Post L-T3 treatment, baseline TSH ranged from 0.1-0.5 mU/L and serum T3 levels were elevated but not different among all groups. Following the administration of L-T3, the average TSH peak induced by TRH in the first generation born to mothers with high TH levels was 6.8±1.0 mU/liter compared to 1.6±0.5 mU/liter (P <0.005) of those born to mothers with normal TH levels. There was no overlap in the TSH responses to TRH between the two groups. The second generation consisted of descendants of grandmothers with high TH levels. Their parents were exposed to TH excess but they themselves were not. In this second generation we found that the offspring of fathers, but not of mothers exposed to high TH levels had RSTH as, after L-T3 treatment, they exhibited a peak TSH response to TRH significantly higher, 6.39 ± 0.63 mU/liter compared to 1.58 ± 0.41 mU/liter (P<0.001), respectively. The third generation was comprised of descendants from great grandmothers with high TH levels. Neither their parents nor themselves were exposed to TH excess during their fetal life. Similarly to the second generation, the offspring of fathers, but not of mothers, had RSTH, as evidenced by significantly higher TSH in response to TRH after L-T3 treatment, 4.60 ± 0.61 mU/liter compared to 1.37 ± 0.23 mU/litter (P<001), respectively. No differences were observed in the PRL responses to TRH and in the peripheral markers of TH action listed above. These findings indicate that fetal exposure to high TH levels causes permanent RSTH, which is transmitted by males but not females with RSTH to individuals of both genders in two subsequent generations.

Safety and Efficacy of Radiofrequency Ablation for Nonfunctioning Benign Thyroid Nodules in Children and Adolescents in 14 Patients over a 10-Year Period

PurposeTo evaluate the efficacy and safety of radiofrequency (RF) ablation for nonfunctioning benign thyroid nodules in children and adolescents. Materials and MethodsFourteen pediatric patients (10 female, 4 male; mean age 15.7 ± 2.3 years, range 12–19 years) with nonfunctioning benign thyroid nodules (mean longest diameter 3.7 ± 1.1 cm, range 2.0–5.6 cm) treated with the use of RF ablation from 2005 to 2015 were evaluated. The inclusion criteria for RF ablation therapy were (i) age <20 years, (ii) benign cytological confirmation by ≥2 separate fine-needle aspiration or core needle biopsies, (iii) pressure symptoms or cosmetic problems caused by thyroid nodules, (iv) absence of any suspicious feature as determined with the use of ultrasound (US), (v) normal serum levels of thyroid hormone and thyrotropin, and (vi) follow-up of >6 months. RF ablation was performed with the use of an RF generator and an 18-gauge internally cooled electrode. RF ablation was performed under local anesthesia without conscious sedation or general anesthesia. Changes in nodules on follow-up US, changes in symptomatic and cosmetic scores, and complications arising during or after RF ablation were evaluated. ResultsMean follow-up period was 36.9 ± 21.7 months (range 6–69 months). At last follow-up visits, mean longest nodule diameter and volume had decreased significantly (3.7 ± 1.1 cm vs 1.4 ± 0.9 cm and 14.6 ± 13.3 mL vs 1.7 ± 4.4 mL; P < 0.001). Both cosmetic and compressive symptoms significantly improved (3.8 ± 0.6 vs 1.4 ± 0.6 and 3.4 ± 1.0 vs 0.1 ± 0.4; P < 0.001). The mean number of ablation sessions was 2.1 ± 1.2 (range 1–5 sessions) and no major complication was encountered during or after RF ablation. ConclusionsRF ablation might be a safe and effective treatment modality for nonfunctioning benign thyroid nodules in children and adolescents.

Influence of subclinical hypothyroidism on indicators of 24-hour arterial blood pressure monitoring in hypertensive patients with high additional risk

Significant prevalence of arterial hypertension (40 % of the adult population) and unsatisfactory level of high blood pressure adequate control (only 14 % of the urban and 8 % of the rural population in Ukraine) underlines the need to study the factors influencing AH course and contributing to a lack of antihypertensive therapy efficacy. One of such factors is subclinical hypothyroidism (SH). Aim. To study Influence of subclinical hypothyroidism on indicators of 24-hour arterial blood pressure monitoring in hypertensive patients with high additional risk. Materials and methods. After signing of written informed consent for the study, 124 patients with arterial hypertension (AH) and 16 practically healthy people (control group) were involved. The main group included 32 AH patients (women 87.5 % (n = 28), men 12.5 % (n = 4)) with moderately elevated thyroid stimulating hormone level (TSH) (4.0–15.6 μD/ml) and normal levels of thyroid hormones. The comparison group consisted of 92 AH patients (women 81.52 % (n = 75), men 18.48 % (n = 17)) with normal levels of TSH (0.4–4.0 μD/ml). The groups of patients were matched for age (54.16 ± 10.16) years versus (57.69 ± 9.76) years, (P = 0.093), sex (P = 0.4319), height (P = 0.993), weight (P = 0.719), body surface area (P = 0.901), body mass index (P = 0.669). All patients underwent a combined 24-hour blood pressure monitoring and ECG using a “Cardiology-04-AD-3” device (St. Petersburg, RF). Results. AH patients with or without concomitant SH were of comparable mean daytime and nighttime indices of SBP and DPB, indicators of SBP and DBP variability, PBP, indices for hypertension and hypotension, circadian indices, indices of percentage SBP and DBP increases, SBP and DBP load (with the exception of daytime SBP load). Patients with AH and SH, in contrast to AH patients without SH, tended to have 8.5 % (P < 0.05) higher indices of daytime SBP load, and 19.3 % (P < 0.05) lower daytime DBP hypotension index. Conclusions . AH patients with or without concomitant SH are comparable by the vast majority of ABPM indicators. However, in AH patients with concomitant SH, unlike those without SH, a larger daytime SBP load and a lower daytime DBP hypotension index were detected.

Clinical study of the radiotherapy with EDGE accelerator in the treatment of the moderate and severe thyroid associated ophthalmopathy.

To explore the short-term efficacy, acute complications and response factors after the radiotherapy with EDGE accelerator in patients with moderate and severe thyroid-associated ophthalmopathy (TAO). A total of 68 patients with moderate and severe TAO who received the radiotherapy with EDGE accelerator between August 1st, 2017 and May 1st, 2011 were enrolled in the present study. The clinical data were collected, and the efficacy and acute complications were followed up, and the response factors were analyzed. Sixty-eight patients (136 eyes) were followed up for 6 months after radiotherapy. The total score after radiotherapy was significantly lower compared to that before the therapy (p<0.05), and the effective rate was 75.74%. After the radiotherapy, the patient's exophthalmia, soft tissue involvement, eye external muscle involvement, corneal involvement, decreased vision and diplopia, tearing and eyelid pain have improved. Acute complications included increased local inflammation, hair loss, pigmentation and xerophthalmias. In addition, multivariate logistic regression analysis demonstrated that thyroid hormone level was the independent factor for the response to the radiotherapy. For patients with moderate and severe TAO, radiotherapy with EDGE accelerator is a safe and effective treatment option. Maintaining normal thyroid hormone level can improve the effective rate of radiotherapy.

Real-time oxidative stress biomarkers measured in patients with Hashimoto’s thyroiditis—an electron paramagnetic resonance study

Although the role of presence of thyroid dysfunction for overproduction of free radicals has been elucidated, the data about the role of autoimmunity in Hashimoto’s thyroiditis (HT) to sustain the presence of oxidative stress despite the normal serum thyroid hormone levels are scarce. The present study aimed by using electron paramagnetic resonance spectroscopy (EPR) methods to elucidate the radical mechanisms included in the pathogenesis of HT by following out the sera levels of some “real-time” oxidative stress biomarkers. We investigated 14 newly diagnosed patients with euthyroid HT and 35 subjects with HT treated with levothyroxine. Twenty-three healthy subjects were included as controls. All samples were measured in triplicate and presented as arbitrary units. We found statistically significant elevated levels of ascorbate radical (Asc•) in euthyroid HT patients and in HT patients treated with levothyroxine compared to controls. Reactive oxygen species (ROS) products were statistically higher in both studied patient groups compared to controls. Our study showed also statistically significant increases in the levels of registered nitric oxide radical (NO•) in both groups of HT patients compared to controls. Oxidative stress is increased similarly in both euthyroid HT and HT patients under treatment with LT4 and these data reinforce the idea that this is consequence of autoimmunity per se. Our results determine that the addition of antioxidants that includes vitamin C and vitamin E in the treatment plan of HT patients in all stages of disease will normalize the disbalance in oxidative stress biomarkers.

Functional features of neutrophils in subclinical hypothyroidism compared to euthyroid status

Neutrophil or polymorphonuclear leukocytes are critical to host defense. They act by migrating (chemotaxis) to site of inflammation or infection, phagocytoze the microorganisms to form phagosome. Reactive Oxygen species and hydrolytic enzymes are released (respiratory burst activity) into this phagosome to kill ingested microorganisms (microbicidal activity). Thyroid hormones are essential for proper differentiation, growth and metabolism of an organism. Increasing evidence indicates that thyroid hormones also play an active role in immunity. Subclinical hypothyroidism is associated with normal thyroid hormone levels with increased thyroid stimulating hormone level. While studies indicate elevated TSH to have some effects on immune functions, there is very little evidence regarding its effect on functional features of neutrophils. In this cross-sectional comparative study, we evaluated the phagocytic, chemotactic, candidacidal, and respiratory burst activity of neutrophils in subclinical hypothyroid and euthyroid subjects. Phagocytosis and metabolic function of the neutrophils was assessed using Nitro-blue tetrazolium test. Chemotaxis, directional movement of the PMNs was measured using the N-Formyl methionyl-leucyl-phenylalanine as chemoattractant. Phagocytic activity was evaluated by exposing leukocytes to candida suspension and counting the number of candida ingested and killed. Microbicidal activity of neutrophils was assessed by the ability of leukocytes to kill Candida albicans in both subclinical hypothyroid and euthyroid subjects. Our study demonstrated that chemotactic and mean phagocytic activity was significantly less in those with subclinical hypothyroidism as compared to euthyroid control group (p value = 0.005 and 0.045 respectively). Respiratory burst activities of both unstimulated &amp; stimulated neutrophils were relatively reduced in subclinical hypothyroidism (p value of 0.08 and 0.07). Candidicidal activity was similar in both groups. We conclude that subclinical hypothyroid individuals having excess of thyroid stimulating hormones are associated altered functional characteristics of neutrophils.

MYOCARDIAL FUNCTIONS IN OBESE CHILDREN WITH SUBCLINICAL HYPOTHYROIDISM

Ponte Academic JournalFeb 2019, Volume 75, Issue 2 MYOCARDIAL FUNCTIONS IN OBESE CHILDREN WITH SUBCLINICAL HYPOTHYROIDISMAuthor(s): Atilla Cifci ,Mehmet BoyrazJ. Ponte - Feb 2019 - Volume 75 - Issue 2 doi: 10.21506/j.ponte.2019.2.11 Abstract:Childhood obesity is an important health problem representing a major public health concern worldwide. An isolated elevation of Thyroid Stimulating Hormone (TSH) with normal levels of thyroid hormones is frequently found in obese children. It has been named Isolated Hyperthyreotropinemia or Subclinical Hypothyroidism (SCH) and may be considered a consequence of obesity. SCH is related to impairment of both systolic and diastolic myocardial function in the adult population. Objective: Aim of this study is to evaluate whether SCH affects myocardial function in childhood obesity. Material and Methods: We examined 48 obese children and adolescents with SCH and 70 obese children and adolescents with normal TSH. Doppler echocardiography was performed in order to evaluate myocardial function to all cases in both groups. Results: Global systolic function was evaluated with, ejection fraction (EF) and compared between groups. Right ventricular global systolic function and pressure were significantly decreased in SCH group. LV mass index was significantly higher in SCH group (p=0.041). Global systolic function was evaluated as EF and no difference was found among the groups. RV global longitudinal function was evaluated with TAPSE measurement and a significant decrease was observed for this value in SCH group compared to the other group (p=0.0015). MAPSE lateral and MAPSE septum which are important for showing LV longitudinal function in SCH group decreased significantly (p=0.004 and p=0.002). Similarly, tissue Doppler imaging (TDI) and peak systolic movement were decreased in SCH group (9,6±1,8 cm/s vs 11.5±1.7 cm/sn; p=0.03). In addition, significant changes were observed in both systolic and diastolic functions in the left ventricle in SCH group. Conclusions: These results suggest the possible involvement of cardiac functions in obese children with SCH. Download full text:Check if you have access through your login credentials or your institution Username Password

Subclinical Hypothyroidism on the Elderly

Subclinical hypothyroidism, defined as an increase of thyroid stimulating hormone levels with normal levels of thyroid hormones, could have a multiorgan impact. There seem to be differences in the elderly (over 65 years of age) which indicate that there should be a different approach in terms of diagnosis and the treatment. Electronic database search and narrative bibliographical review. Different case studies showing the multiorgan consequences of subclinical hypothyroidism suggest that, in the elderly, there is a minor impact or even a lack of repercussion, especially in those over 80 - 85 years old. Additionally, there is evidence indicating that the levels of thyroid stimulating hormone rise with the age of the patient. The standard treatment, in the beginning, is a low dose of levothyroxine when the levels of thyroid stimulating hormone are over 10.0 mIU/L, when there are noticeable symptoms or positive anti-thyroid antibodies. However, the treatment is not consensual when the levels of thyroid stimulating hormone are between 4.5 and 10.0 mIU/L, in such a way that the TRUST study concluded that no benefits have outcome from treating these patients. The non-definition of the reference range and the age gap are the key factors that contribute the most to biased results. However, there is consensus regarding non-treatment of mild thyroid dysfunctions (4.5 - 7.0 mIU/L) in the elderly, particularly above 80 years of age. Nevertheless, for positive anti-thyroid antibodies, suggestive ultrasound changes or iatrogenic side effects, the reference level should be 4.5 mIU/L. The general impact of subclinical hypothyroidism is different in elderly people, meaning that an individualized therapeutic approach and long-term monitoring is the appropriate strategy.

BS14. Visual and brainstem auditory evoked potentials in Hashimoto’s thyroiditis

Introduction A normal thyroid gland activity is essential for the optimal development, maturation and function of the nervous system. Neurological syndromes can develop in certain thyroid diseases that may have normal levels of thyroid hormones. One such example is Hashimoto’s thyroiditis (HT), which is currently considered to be the most common autoimmune disease in humans. The exact cause of those symptoms has not yet fully been explained. Their pathomechanism is still being studied. Precise and non-invasive methods of assessment of the nervous system function is evoked potentials study (EP). It is a sensitive technique that enables the evaluation of the brain bioelectrical activity also in patients with HT. EPs are particularly useful in patients with mild or without clinical neurological symptoms. The aim of the study was to evaluate parameters of visual and brainstem auditory evoked potentials (VEP, BAEP) in euthyreotic HT patients without clinical neurological deficit, and without ophthalmological and otolaryngological abnormalities. Methods 100 HT patients (92 women, 8 men) from 20 to 68 years old (mean 46.9 years). They did not suffer from concurrent diseases that could have affected the brain electrical activity. The visual and auditory receptors were not damaged in any of the patients and the patients did not suffer from any central nervous system damage. The matched control group comprised 50 healthy subjects. HT patients underwent a subjective and objective neurological examination, thyroid hormone levels and thyroid autoantibody titers, brain imaging (CT or MRI), VEP and BAEP. Results Abnormal VEP and BAEP were recorded in 34% of the patients. The mean P100, relative P100, N145 VEP latencies were significantly longer and P100 amplitude significantly higher in HT patients than in the control group. HT patients also had a longer mean wave V latency and mean wave III-V and I-V interpeak latencies and significantly lower mean wave I and V amplitudes than the controls. There were no statistically significant correlations between the mean VEP parameters and the levels of TSH, free thyroid hormones, antithyroid antibody titers and the applied dose of L-thyroxine. There was a relationship between the level of TSH and the wave BAEP III-V interpeak latency. The number of abnormal VEP and BAEP depended on the dose of L-thyroxine and was the highest in patients without treatment and decreased with the increase in the dose of levothyroxine. Conclusion 1. There were changes in the brain bioelectrical activity in the form of abnormal VEP and BAEP in one third of the patients with Hashimoto’s disease who did not have central nervous system deficits. 2. The increased amplitude of the VEP in the course of HT may indicate increased cerebral cortex activity. 3. Disorders of the brain bioelectrical activity in the course of HT may be associated with an ongoing autoimmune process. 4. The analysis of the VEP and BAEP may be useful in assessing the brain bioelectrical activity in the course of HT.

Asymptomatic thyroid dysfunction in human immunodeficiency virus-1-infected subjects.

BACKGROUND:Thyroid hormone abnormalities have been reported elsewhere in human immunodeficiency virus-1 (HIV-1)-infected individuals, but such studies in Nigerians are scarce in literature.OBJECTIVE:To evaluate thyroid function in HIV-1-infected individuals and to correlate thyroid function parameters with cluster of differentiation (CD4+) cell count.MATERIALS AND METHODS:Total thyroxine (T4), total triiodothyronine (T3), thyroid-stimulating hormone (TSH), and CD4+ were estimated in 100 HIV-1-positive individuals on highly active antiretroviral therapy (HAART), 100 HIV-1-positive HAART naïve, and 100 HIV-1-negative controls. The mean values were compared between the groups, and CD4+ cell count was correlated with measured thyroid hormones.RESULTS:Thyroid function abnormalities were seen in 52 HIV-1-positive individuals on HAART and 56 individuals without HAART treatment. The pattern of thyroid hormone abnormalities is similar in both groups. Among the individuals on HAART, 10 had subclinical hypothyroid, 42 sick euthyroid, and 48 had normal thyroid hormones levels. Similarly, among those without HAART therapy, seven had subclinical hypothyroid, 49 sick euthyroid, and 44 had normal thyroid hormones levels. The HIV-1-positive individuals had significantly lower (P < 0.001) CD4+ cell count, TSH (P < 0.05), T3 (P < 0.01), and T4 (P < 0.001) when compared with controls. On the other hand, HIV-1-positive individuals on HAART had significantly higher (P < 0.01) CD4+ cell count and lower (P < 0.05) T4 levels than the HAART naïve group. CD4+ correlated positively with T4 in HIV-1-positive individuals on HAART (r = 0.26; P = 0.016) and HAART naïve (r = 0.218; P = 0.038). There was no significant correlation between CD4+ and measured thyroid hormones in the control individuals.CONCLUSION:Asymptomatic thyroid hormone abnormalities are common in HIV-infected individuals, and these abnormalities are independent of whether the individuals were on HAART or without HAART treatment.

Association between Thyroid Hormone Levels and Diabetic Kidney Disease in Euthyroid Patients with Type 2 Diabetes

The association between normal thyroid function and diabetic kidney disease (DKD) has gained increasing attention. The present study evaluated the relationship between normal thyroid hormone levels and DKD in type 2 diabetes mellitus (T2DM) patients. A total of 862 type 2 diabetes patients were enrolled in this cross-sectional study in Xi’an, Shaanxi Province, China. The subjects were evaluated for anthropometric measurements, thyroid function and DKD. Of 862 patients, 246 (28.5%) suffered from DKD, and the prevalence of DKD did not differ between men and women. The prevalence of DKD showed a significantly decreasing trend across the quartiles based on free triiodothyronine (FT3) levels (41.1%, 30.6%, 23.8%, and 18.9%, P < 0.001). In comparison with all participants categorized in the first FT3 quartile group (FT3-Q1) (<4.380), the adjusted odds ratio of DKD in the second FT3 quartile group (FT3-Q2), the third FT3 quartile group (FT3-Q3), and the fourth FT3 quartile group (FT3-Q4) were 0.655(95%CI: 0.406–1.057), 0.493(95%CI: 0.299–0.813), 0.406(0.237–0.697) (P < 0.05). Also, similar results were observed in men. Conversely, none of the FT3 groups was associated with DKD in women. The present study showed that FT3 within normal range was negatively correlated with DKD in T2DM patients.

Značaj antropometrijskih parametara kod bolesnika sa subkliničkom hipotireozom

Introduction: The concept of subclinical thyroid disease appeared in the 1980s when sensitive procedures for the measurement of the thyroid-stimulating hormone in the serum were introduced. Subclinical hypothyroidism is defined by the finding of elevated serum TSH concentrations with normal thyroid hormone levels. The incidence of subclinical hypothyroidism with increased cardiovascular risk has not yet been fully clarified. The aim of the study was to identify anthropometric parameters that may indicate an increased cardiometabolic risk in patients with subclinical hypothyroidism. Method: The study will include 140 patients aged 18-65, with 105 patients with subclinical hypothyroidism and a control group of 35 healthy, normally nourished subjects without subclinical hypothyroidism. A program of research will be carried out in all patients and it will include: detailed anamnesis and physical examination, anthropometric measurements (weight measurements, body height, waist circumference, hip circumference, body weight mass measurement by the bioelectrical impedance analysis method (%BFP), calculation of: body mass index (BMI), waist-to-hip circumference ratio (WC/HC), waist-to-height ratio (WC/Ht) and laboratory testing (FT3, FT4, TSH). Results: Examinees with subclinical hypothyroidism had statistically significantly elevated mean TSH values (6.87 + 1.34 mIU/ml) compared to TSH euthyroid examinees (1.9 + .88 mIU/ml). The mean age of subjects with subclinical hypothyroidism was 44.15 ± 11.23 years (MA = 43 years), and in subjects without subclinical hypothyroidism, 33.80 ± 10.60 years (MA = 33 years). In relation to the control group (euthyroid patients), patients with subclinical form of hypothyroidism had higher average mean values and statistically significantly higher incidence of elevated values: BMI (T test = 7.465, p &lt; 0.0001; 2 = 35.977, p &lt; 0.0001), %BFP (T test = 8.594, p &lt; 0.0001; 2 = 44.956, p &lt; 0.0001), WC (T test = 6.262, p &lt; 0.0001; 2 = 48.865, p &lt; 0.0001), and WC/Ht ratio (T test = 7.372, p &lt; 0.0001; 2 = 39.175, p &lt; 0.0001). The WC/HC ratio in the group with subclinical hypothyroidism was higher than in the group without subclinical hypothyroidism, but not statistically significant (T test = -0.946, p = ns; 2 = 0.622, p = 0). Conclusion: In the subclinical form of hypothyroidism, changes in the degree of nutrition and body weight can already be recorded, which, among other things, contributes to the development of increased cardiometabolic risk.

Serum levels of nitrite/nitrate, lipid profile, and Fasting Plasma Glucose and their associations in subclinical hypothyroid women before and after a two month treatment by levothyroxine.

Subclinical hypothyroidism (sHT) is a condition defined by elevated TSH values with normal levels of free thyroid hormones. Altered metabolic status is one of the consequences of sHT which can affect serum levels of FPG, lipid profile, and nitric oxide which propounds cardiovascular consequences per se. The aim of this study was to determine the possible effects of sHT on nitrite/nitrate levels, as a marker of endothelial performance. 50 females were enrolled in this study, 25 women as control group and 25 women as case group (evaluated two times: before and after levothyroxine therapy). Blood samples were collected and levels of FPG, lipid profile components, and nitric oxide were measured spectrophotometrically. The data were analyzed using SPSS version 18 software. The levels of lipid profile (except for TG between before and after group, p < 0.05) and nitric oxide did not differ in groups while FPG was significantly higher in case groups in comparison to control group (p < 0.001). Nitric oxide had no correlations with any of variables except for LDL in after treatment group (p < 0.05 and r = 0.397). Nitric oxide does not have correlation with components of lipid profile (except for LDL) or FPG and has no differences in subclinical hypothyroid patients and control group. Levothyroxine therapy during 2 months cannot alter the levels of nitric oxide in subclinical hypothyroid patients.

Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis

Variations in level of thyroid-stimulating hormone (TSH) within the reference range of thyroid hormone could have negative health effects. We evaluated the effect of plasma TSH levels within the euthyroid range on the severity of histological damage associated with nonalcoholic fatty liver disease (NAFLD). We performed a cross-sectional study of 425 subjects with biopsy-proven NAFLD (mean age, 53 years; 52% male) who participated in the Boramae NAFLD study from January 2013 to January 2017. Each subject underwent an anthropometric assessment and laboratory and clinical evaluations. Of the subjects, 282 were assigned to a strict-normal thyroid function group (plasma level of TSH, 0.4 to 2.5 mIU/L). Patients with low thyroid function were assigned to groups of subclinical hypothyroidism (plasma level of TSH above 4.5 mIU/L with a normal thyroid hormone level; n = 59) or low-normal thyroid function (higher plasma TSH level [2.5 to 4.5 mIU/L] with a normal thyroid hormone level; n = 84). Multivariate logistic regression analysis was used to identify factors independently associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis. NASH and advanced fibrosis were found in higher percentages of subjects with low thyroid function vs strict-normal thyroid function (52.4% vs 37.2% for NASH and 21.0% vs 10.6% for advanced fibrosis; P < .01). Among subjects with low thyroid function, a higher proportion of patients with subclinical hypothyroidism had NASH and associated advanced fibrosis vs patients with low-normal thyroid function (57.6% vs 48.8% for NASH and 25.4% vs 17.9% for advanced fibrosis; P < .01). Subjects with low thyroid function had more extensive hepatic steatosis with greater severity of balloon degeneration and fibrosis. In multivariate analyses, low thyroid function was significantly associated with NASH (odds ratio, 1.61; 95% CI, 1.04-2.50; P = .035) and advanced fibrosis (odds ratio, 2.23; 95% CI, 1.18-4.23; P = .014). Risks of NASH and advanced fibrosis increased significantly with plasma concentration of TSH (Ptrend <.05 for each). Subclinical hypothyroidism and low-normal thyroid function are independent predictors of NASH and advanced fibrosis, confirming the relationship between these diseases. ClinicalTrials.gov, Number: NCT02206841.

Insulin resistance and normal thyroid hormone levels: prospective study and metabolomic analysis.

While hyperthyroidism and hypothyroidism cause dysglycemia, the relationship between thyroid hormone levels within the normal range and insulin resistance (IR) is unclear. In 940 participants with strictly normal serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) followed up for 3 yr, we measured insulin sensitivity (by the insulin clamp technique) and 35 circulating metabolites. At baseline, across quartiles of increasing fT3 levels (or fT3/fT4 ratio) most features of IR emerged [i.e., male sex, greater body mass index (BMI), waist circumference, heart rate, blood pressure, fatty liver index, free fatty acids, and triglycerides; reduced insulin-mediated glucose disposal; and β-cell glucose sensitivity). In multiadjusted analyses, fT3 was reciprocally related to insulin sensitivity and, in a subset of 303 subjects, directly related to endogenous glucose production. In multiple regression models adjusting for sex, age, BMI, and baseline value of insulin sensitivity, higher baseline fT3 levels were significant predictors of decreases in insulin sensitivity. Moreover, baseline fT3 predicted follow-up increases in glycemia independently of sex, age, BMI, insulin sensitivity, β-cell glucose sensitivity, and baseline glycemia. Serum tyrosine levels were higher with IR and were directly associated with fT3; higher α-hydroxybutyrate levels signaled enhanced oxidative stress, thereby impairing tyrosine degradation. In 25 patients with morbid obesity, surgery-induced weight loss improved IR and consensually lowered fT3 levels. High-normal fT3 levels are associated with IR both cross-sectionally and longitudinally, and predict deterioration of glucose tolerance. This association is supported by a metabolite pattern that points at increased oxidative stress as part of the IR syndrome.

Thyroid-stimulating hormone stimulation downregulates autophagy and promotes apoptosis in chondrocytes

Subclinical hypothyroidism (SCH) patients have normal thyroid hormone levels but increased thyroid stimulating hormone (TSH) level in serum. It has been reported that high TSH is related to abnormal skeletal development in mice with hypothyroidism. However, the cellular mechanism is not fully understood. In the present study, we aim to investigate the direct effects of TSH stimulation on chondrocytes, and the putative role of autophagy in this process. By using EdU incorporation assay and flow cytometry for mitochondrial membrane potential assay, we demonstrated deceased proliferation and promoted apoptosis in TSH stimulated primary mouse chondrocytes. And the balance of Bcl-2 and BAX expression on protein level was broken. More interestingly, the expression of autophagic markers Beclin-1 and LC3II was reduced in TSH stimulated chondrocytes, accompanied by less autophagosomes and accumulated p62 protein, indicating an impaired autophagic flux. More interestingly, mTOR was upregulated and AMPK activity was decreased in TSH stimulated PMCs, suggesting that mTOR/AMPK pathway is get involved in the regulation of TSH on autophagy in PMCs. Collectively, we found an increased apoptosis and suppressed autophagy in TSH stimulated primary chondrocytes, which is meaningful in understanding the effects of increased TSH level on articular cartilage and the role of autophagy in this process, and thus provide a potential novel therapeutic target in related cartilage damages.

Cholesterol Synthesis Increased in the MMI-Induced Subclinical Hypothyroidism Mice Model.

Subclinical hypothyroidism (SCH) is defined as increased serum thyroid-stimulating hormone (TSH) concentrations and normal serum thyroid hormone (TH) levels as well as an increased serum cholesterol level, which is an important cause of secondary hypercholesterolemia and cardiovascular diseases. Some studies have demonstrated a direct effect of TSH on cholesterol metabolism via in vivo and in vitro experiments. However, because no suitable SCH model has been established until now, the changes in cholesterol synthesis that occur in SCH patients remain unknown. Here, we establish an SCH mouse model by using long-term low-dose MMI administered in drinking water. Compared with the control group, the MMI-treated mice had elevated circulating TSH levels, but the serum FT3 levels in these mice did not change. Additionally, the TC levels increased in both the serum and liver of the experimental mice. Both the protein expression and activity of hepatic HMGCR, the rate-limiting enzyme for cholesterol synthesis in the liver, increased in these mice. We also found that the SCH mice had decreased phospho-HMGCR and phospho-AMPK expression, while the expression of AMPK showed no change. In conclusion, we established a suitable SCH model in which cholesterol synthesis is increased.

NO-mediated anticontractile effect of the endothelium is abolished in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism

IntroductionThyroid hormones are essential for proper development of many systems and organs, including circulatory system. Thyroid deficiency during pregnancy may affect the cardiovascular function in children early on and later in adulthood. However, long-term effects of early thyroid deficiency are poorly understood. We hypothesized that antenatal/early postnatal hypothyroidism will influence anticontractile effect of NO in coronary arteries of adult rats. Design and methodsTo model antenatal/early postnatal hypothyroidism dams were treated with 6-propyl-2-thiouracil (PTU) in drinking water (0.0007%, w/v) from the first day of pregnancy till 2 weeks after delivery. Control females were supplied with pure water. Their male offspring was grown up till the age of 10–12 weeks. Systolic blood pressure was measured using tail cuff method. Septal coronary arteries were isolated and studied in wire myograph. Blood serum thyroid hormones concentrations (ELISA) and NO metabolites level (Griess method) were evaluated. ResultsAt the age of 10–12 weeks thyroid hormones, TSH concentrations, NO metabolites and systolic blood pressure level didn't differ between groups. Arterial responses to acetylcholine and exogenous NO-donor DEA/NO were similar in control and PTU groups. Along with that, in control rats endothelium denudation strongly potentiated basal tone of arteries and their contractile responses to thromboxane A2 receptor agonist U46619. The effects of endothelium denudation were absent in PTU rats indicating that anticontractile effect of endothelium is abolished in their arteries. Further, NO-synthase inhibitor L-NNA (100 μM) caused significant elevation of basal tone and increased U46619-induced contraction of endothelium-intact arteries only in control rats, while had no effect in PTU group. ConclusionsOur data demonstrate that NO-mediated anticontractile effect of endothelium is eliminated in coronary arteries of adult rats, which suffered from antenatal/early postnatal hypothyroidism. Therefore, maternal thyroid hormones deficiency may have detrimental consequences in adult offspring including coronary circulation pathologies, despite normal blood levels of thyroid hormones.