Decrease In Free T3 Research Articles

Exposure to Multiple Per- and Polyfluoroalkyl Substances In Relation To Thyroid Function Among Adolescents and Young Adults from NHANES 2011-2012

BACKGROUND AND AIM: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals with a wide range of industrial applications, measured in human serum samples. Experimental studies have identified PFASs as endocrine disrupting chemicals and epidemiological studies suggest that PFASs can affect normal thyroid function in humans. We investigated the association between exposure to mixtures of serum PFASs and changes in serum thyroid hormone levels among 12 to 20 year olds. METHODS: Using data from the NHANES 2011-2012 cycle, we employed principal component analysis (PCA) and identified three factors, describing mixtures of PFASs. Using multivariable linear regression models, we estimated associations between exposure to PFAS mixtures and changes in serum thyroid hormone concentrations. RESULTS:Factor 1 was characterized by carboxylates, comprising of PFUnA, PFDA, and PFNA, Factor 2 was described by sulfonates which included PFHxS, PFOS, PFA, and MeFOSAA and Factor 3 was described PFHpA alone. Greater exposure to Factor 1 PFASs was associated with an overall increase in free T4, TSH, and thyroid peroxidase antibodies levels, without any statistical significance. Exposure to Factor 2 PFASs was associated with an overall decrease in free T3, total T3, free T4, and total T4 levels. Factor 3 resulted in an increase in most of the serum thyroid hormone levels with the exception of thyroglobulin and thyroglobulin antibodies levels. CONCLUSIONS:Our results suggest the importance of modeling the effects of exposure to a mixture of PFASs simultaneously. The findings of this analysis can better inform researchers and policy makes on which PFASs behave analogously or inversely in an effort to better assess the effect PFASs may have on health effects. KEYWORDS: biomarkers, chemical mixtures, endocrine disruptors, polyfluoroalkyl substances, thyroid function

Особливості гормонального тестування тиреоїдної функції у пацієнтів із цукровим діабетом 1-го типу і хронічною хворобою нирок

Актуальність. Перебіг хронічної хвороби нирок (ХХН) може впливати на метаболізм тиреоїдних гормонів. Встановлено, що зниження ниркової функції може поєднуватися зі змінами функції щитоподібної залози (ЩЗ). Тиреоїдна дисфункція також має наслідки для ренального потоку крові, швидкості клубочкової фільтрації (ШКФ), канальцевого транспорту, електролітного гомеостазу та структури клубочків. Мета дослідження— визначити особливості функції ЩЗ у пацієнтів із цукровим діабетом (ЦД) 1-го типу та ХХН, на підставі чого розробити рекомендації щодо термінів гормонального тестування тиреоїдної патології. Матеріали та методи. З метою визначення оптимальних термінів гормонального тестування була проведена оцінка тиреоїдної функції у 121 пацієнта з ЦД 1-го типу та ХХН. Пацієнти з ЦД 1-го типу та ХХН були розділені на 3 групи: перша— 78 осіб із ШКФ ≤ 60 мл/хв/1,73 м2, група 2— 20 осіб, які отримують нирково-замісну терапію (НЗТ), група 3— 23 особи після трансплантації нирки (ТН) з адекватною функцією трансплантату (тривалість роботи ниркового трансплантату— 3,62 (1,47–4,28) року). Результати. У пацієнтів із ЦД 1-го типу та ХХН знижена діагностична цінність рівня тиреотропного гормону (ТТГ) у зв’язку з відсутністю відмінностей його значень при зниженні вільного тироксину (вТ4) і вільного трийодтироніну (вТ3). Найбільш чутливим маркером тиреоїдної дисфункції є вТ3. Генез тиреоїдних порушень у пацієнтів з ЦД 1-го типу та ХХН має неімунну природу. У пацієнтів із ЦД 1-го типу, які отримують НЗТ, після процедури гемодіалізу відбувається збільшення периферичних загальних вТ4 і вТ3, що обумовлює необхідність моніторингу функціональних порушень ЩЗ безпосередньо після проведення сеансу гемодіалізу. Після ТН відбувається відновлення нормальних значень індексу периферичної конверсії (ІПК) і вТ3 протягом 1–2 років залежно від тривалості отримання НЗТ. У пацієнтів із ЦД 1-го типу з тривалістю роботи ренотрансплантату більше трьох років відбувається збільшення ІПК, що характеризує дисбаланс периферичних тиреоїдних гормонів у бік зниження вТ3 при відносно стабільному вТ4. Висновки. Тиреоїдні дисфункції характерні для всіх стадій патологічного процесу при ХХН у пацієнтів із ЦД 1-го типу, включаючи пацієнтів на термінальній стадії і після успішної трансплантації нирки. Зміни тиреоїдних гормонів асоційовані з тривалістю НЗТ, тривалістю роботи ренотрансплантату, а також можуть потенційно впливати на виживання пацієнтів після ТН.

The Relationship Between Thyroid Function and Body Composition, Leptin, Adiponectin, and Insulin Sensitivity in Morbidly Obese Euthyroid Subjects Compared to Non-obese Subjects.

Background/Objectives:Thyroid function tests (TFTs) changes in obese people have been studied with increasing interest, however, studies have been inconsistent hence it remains poorly understood. We compared the TFTs of morbidly obese euthyroid Saudi subjects with non-obese controls and then we examined the influence of leptin, adiponectin, and insulin resistance on TFTs.Subjects/Methods:Fifty-five euthyroid obese subjects attending bariatric surgery clinic and 52 non-obese age-and gender-matched controls were recruited. We measured body weight, BMI, body composition, thyroid-stimulating hormone (TSH), Free T4 (FT4), Free T3(FT3), thyroid antibodies, fasting leptin, adiponectin, and lipid profile. Insulin resistance was quantified by HOMA-IR. Data are presented as mean ± SEM.Results:Mean BMI was 45.6 ± 1.5 and 23.2 ± 0.5 kg/m2, for the obese and non-obese controls, respectively, P value < 0.001. Mean TSH was 2.7 ± 0.18 mIU/L in obese subjects and 1.7 ± 0.13 mIU/L (0.27-4.2) in the non-obese controls, respectively, P value .014. Mean FT3 was 3.9 ± 0.1 pmol/L (3.1-6.8) in obese subjects compared to 5.0 ± 0.1 pmol/L in non-obese controls, respectively, P value 0.001, however, FT4 was similar in the 2 groups. In the whole group (N = 107), BMI correlated positively with TSH and negatively with FT3. Leptin correlated negatively with both FT4 and FT3 in the non-obese group only while none of the TFTs correlated with HOMA-IR or adiponectin in either group. Binary logistic regression showed that each 1 unit increase in TSH increased the odds of becoming obese by 12.7, P value 0.009, 95 C.I. (1.9-85.0). Conversely, each - unit increase in FT3 decreased the odds of becoming obese by 0.2, P value 0.023, 95% C.I. (0.05-0.80).Conclusions:We report a small increase in TSH and a small decrease in FT3 within the normal range in obese subjects compared to non-obese controls. We also report a positive correlation between TSH and BMI with increased odds ratio of becoming obese with the increase in TSH and decrease in FT3. These changes may be either causally related or adaptive to the obesity state. FT4 and FT3 seem to correlate with leptin (but not with adiponectin or HOMA-IR) in the non-obese controls only. Larger mechanistic studies are needed to further elucidate the interesting association between obesity and TFTs.

Effect of vitamin D3 on thyroid function and de-iodinase 2 expression in diabetic rats

Objective: This study aimed to assess the effect of vitamin D3 administration to diabetic rats on thyroid profile and deiodinase 2 (D2). Methods: Thirty male Wistar rats were included into three groups; control, streptozotocin-induced diabetic and diabetic supplemented with vitamin D3 groups. Ten weeks later, serum levels of free T4, free T3 and TSH were measured. Tissue homogenates from liver, kidney, muscle, femur bone, heart and brain were obtained and assessed for D2 mRNA. Results: Diabetic rats demonstrated significant increase in free T4 and significant decrease in free T3. These changes were ameliorated by vitamin D3 administration. D2 mRNA was significantly reduced in all tissue homogenates obtained from diabetic rats, while vitamin D3 treatment significantly enhanced D2 in liver and brain homogenates. Conclusion: Diabetes mellitus inhibited peripheral conversion of T4 into T3 secondary to reduction in D2 expression. Vitamin D3 greatly corrected the alterations in thyroid profile and D2 expression.

Mechanisms of Normalisation of Bone Metabolism during Recovery from Hyperthyroidism: Potential Role for Sclerostin and Parathyroid Hormone

Sclerostin, a protein expressed by osteocytes, is a negative regulator of bone formation. The aim of the study was to investigate the relationship between parathyroid hormone (PTH) and markers of bone metabolism and changes of sclerostin concentrations before and after treatment of hyperthyroidism. Patients and Methods. The study involved 33 patients (26 women), age (mean ± SD) 48 ± 15 years, with hyperthyroidism. Serum sclerostin, PTH, calcium, and bone markers [osteocalcin (OC) and collagen type I cross-linked C-telopeptide I (CTX)] were measured at diagnosis of hyperthyroidism and after treatment with thiamazole. Results. After treatment of hyperthyroidism a significant decrease in free T3 (FT3) and free T4 (FT4) concentrations was accompanied by marked decrease of serum sclerostin (from 43.7 ± 29.3 to 28.1 ± 18.4 pmol/L; p < 0.001), OC (from 35.6 ± 22.0 to 27.0 ± 14.3 ng/mL; p < 0.001), and CTX (from 0.49 ± 0.35 to 0.35 ± 0.23 ng/dL; p < 0.005), accompanied by an increase of PTH (from 29.3 ± 14.9 to 39.8 ± 19.8; p < 0.001). During hyperthyroidism there was a positive correlation between sclerostin and CTX (r s = 0.41, p < 0.05) and between OC and thyroid hormones (with FT3 r s = 0.42, with FT4 r s = 0.45, p < 0.05). Conclusions. Successful treatment of hyperthyroidism results in a significant decrease in serum sclerostin and bone markers concentrations, accompanied by an increase of PTH.

Effect of vitamin D3 supplementation on thyroid hormones and deiodinase 2 expression in streptozotocin‐induced diabetic rats (688.9)

Aim: The present study aimed to assess the effect of vitamin D3 administration on deiodinase 2 (D2) mRNA expression in various tissues of diabetic rats.Methods: Thirty male Wistar rats (200‐250 g) were included into; control, diabetic and diabetic supplemented with vitamin D3 groups. Diabetes was induced by single intraperitoneal injection of streptozotocin 45 mg/kg. Vitamin D3 was administered orally in a dose of 500 IU/kg/day in olive oil for 10 weeks. Serum levels of free T4, free T3 and TSH were measured. Tissue homogenates from liver, kidney, muscle, femur bone, heart and brain were obtained and assessed for expression of D2 mRNA.Results: Diabetic rats demonstrated significant increase in free T4 and significant decrease in free T3 with non significant increase in TSH compared to control rats. The changes in thyroid profile were ameliorated by vitamin D3 administration to diabetic rats. D2 mRNA expression was significantly reduced in all tissue homogenates of diabetic rats, however vitamin D3 did enhance D2 mRNA expression especially in liver and brain of diabetic rats.Conclusion: Diabetes mellitus inhibited peripheral conversion of T4 into T3 secondary to reduction in the expression of D2 in almost all body tissues. Vitamin D3 greatly corrected the alterations in thyroid profile and D2 expression in diabetic rats and protected against the subclinical hypothyroid state that could associate diabetes mellitus.Grant Funding Source: No

The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid

BackgroundNanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets.ObjectiveThe objective of this study was to determine the protective ability of selenium nanoparticles against hexavalent chromium-induced thyrotoxicity.DesignTwenty male rats were used in the study, and arbitrarily assigned to four groups. Group 1 was the control group, and was given phosphate-buffered saline. Group 2 was the chromium-treated group and was given K2Cr2O7 60 μg/kg body weight intraperitoneally as a single dose on the third day of administration. Group 3 was the nano-selenium-treated group and was given selenium nanoparticles (size 3–20 nm) 0.5 mg/kg body weight intraperitoneally daily for 5 consecutive days. Group 4 was the nano-selenium chromium-treated group, which received selenium nanoparticles for 5 days and a single dose of K2Cr2O7 on the third day of administration.Materials and methodsBlood samples were collected from rats for measuring thyroid hormones (free triiodothyronine [T3] and free thyroxine [T4]) and oxidative and antioxidant parameters (malondialdehyde [MDA], reduced glutathione [GSH], catalase, and superoxide dismutase [SOD]). Upon dissection, thyroid glands were taken for histopathological examination by using paraffin preparations stained with hematoxylin and eosin (H&E) and Masson’s trichrome. Immunohistochemical staining was performed for detecting cellular proliferation using Ki67 antibodies.ResultsThe present study shows that K2Cr2O7 has a toxic effect on the thyroid gland as a result of inducing a marked oxidative damage and release of reactive oxygen species. This was shown by the significant decrease in free T3 and T4 and GSH levels, which was accompanied by significant increases in catalase, SOD, and MDA in the chromium-treated group compared to the control group. Se nanoparticles have a protective effect on K2Cr2O7-induced thyroid damage, as a result of correcting the free T3 and T4 levels and GSH, catalase, SOD, and MDA compared to the K2Cr2O7-treated group. Administration of nano-selenium alone in the nano-selenium-treated group had no toxic effect on rats’ thyroid compared to the control group. The biochemical results were confirmed by histopathological, immunohistochemical and pathomorphological studies.

Successful treatment of thyrotoxicosis is accompanied by a decrease in serum sclerostin levels

Sclerostin, a product of a SOST gene, is a protein expressed by osteocytes that inhibits osteoblastic bone formation. Several hormones, including PTH and glucocorticosteroids, have been suggested to be possible regulators of sclerostin production. The influence of thyroid hormones on sclerostin synthesis has not been investigated, so far. The aim of the study was to evaluate sclerostin concentrations in patients before and after treatment of thyrotoxicosis.Patients and methodsThe study involved 15 patients (4 men), mean age 51.8±15.3 years, mean BMI value - 24.7±3.5, with thyrotoxicosis due to Graves’ disease or toxic multinodular goitre. Serum sclerostin was measured by immunoassay at diagnosis of thyrotoxicosis and after 6–10 weeks of treatment with thiamazole. The data were analysed by means of simple descriptive statistics of location and dispersion and Mann–Whitney U test for pairs of results, before and after thiamazole therapy. Association between variables was evaluated with use of Spearman`s correlation coefficient.ResultsThere was a significant decrease in free T3 (FT3) and free T4 (FT4) concentrations (from 8.74±4.79 pg/ml to 3.54±2.40 pg/ml, and from 4.48±2.21 ng/ml to 1.02±1.07 ng/ml, respectively, p<0.001). This was accompanied by a marked decrease of serum sclerostin levels from 55.46±20.90 pmol/l to 35.73±15.70 pmol/l, p<0.0015). Interestingly, enough, sclerostin levels did not correlate with serum FT3 or FT4 concentrations.ConclusionsRestoration of a euthyroid state in patients with thyrotoxicosis results in a significant decrease in serum sclerostin concentrations. The above mentioned phenomenon may reflect lowering of bone metabolism, but a possible direct influence of thyroid hormones on SOST gene needs to be investigated.

Endemic goitre in Senegal--thyroid function etiological factors and treatment with oral iodized oil.

Endemic goitre and its response to orally administered iodized oil has been studied in seven villages 25-30 km south of Velingara, Eastern Casamance, Senegal. In 502 adults aged greater than 15 years goitre prevalence was 62% with 18.2% having goitre grade 2 or 3. Mean free T4 (FT4) was 11.9 +/- 3.5 (SD) pmol/l and iodine deficiency was confirmed by noting median urinary I of 0.079 mumol/l (14.9 mumol I/mol creatinine) with elevated free T3 (FT3)/FT4 ratios. Serum selenium concentrations were normal. The response to 480 mg of oral iodized oil assessed at 6 and 12 months was characterized by a 35.8% increase in FT4, a 25% decrease in FT3 and a 50% decrease in TSH (all p less than 0.01) at 12 months associated with a significant decrease in goitre size measured in 70 persons when compared to 65 controls not receiving iodine. Urinary iodine rose from 0.071 mumol/l to 0.189 mumol/l (p less than 0.01) during this time and no adverse effects on thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) were observed. A variation in goitre prevalence between villages was noted which, in such a small geographical area, suggests that etiological factors in addition to iodine deficiency may be important in goitre pathogenesis. Oral iodized oil administration is an effective treatment for iodine deficiency goitre in the short term.

Effects of short‐term 17β‐estradiol treatment on the properties of t3‐binding proteins in the plasma of immature rainbow trout, salmo gairdneri

AbstractTo determine the effects of 17β‐estradiol (E2) on theproperties of the plasma proteins that bind 3,5,3′‐triiodo‐L‐thyronine (T3), immature rainbow trout, Salmo gairdneri, were intraperitoneally injected on days 0 and 3 with 0.5 mg E2‐3‐benzoate/100 g body weight, and plasma was sampled on days 4, 7, or 12. Control trout received peanut oil alone. E2 increased significantly the proportion of [125I]T3 bound to plasma‐binding sites. Separation of plasma proteins of control trout by agarose filtration on Bio‐Gel A‐1.5 m revealed that T3 bound to two main sites corresponding to molecular weights of 130 kDa (presumed prealbumin) and 55 kDa (presumed β‐globulin). Addition of a calculated amount of unlabeled T3 displaced [125I]T3 from the 55 kDa site, indicating its role as the T3 high‐affinity and low‐capacity site. E2 treatment initiated production of vitellogenin, which did not bind T3. Saturation analysis of [125I]T3 binding conducted on miniature G‐25 Sephadex columns indicated that E2 increased the capacity of the low‐affinity, high‐capacity T3‐binding site without effect on the high‐affinity, low‐capacity T3‐binding site. In conclusion, T3 binds to two main plasma sites and E2 causes an increase in the capacity of the low‐affinity site, resulting in a decrease in free T3 and in possible changes in T3 availability to tissues.

The effect of propranolol on circulating thyroid hormone measurements in thyrotoxic and euthyroid subjects.

Circulating concentrations of total and free thyroid hormones and thyroid hormone binding proteins were measured in thyrotoxic and euthyroid subjects treated with propranolol. In the thyrotoxic group, total triiodothyronine (T3) concentration fell after propranolol therapy, suggesting an effect of the drug on the peripheral conversion of thyroxine (T4) to T3. In euthyroid subjects, a rise in circulating concentrations of free T4 and reverse T3 (rT3) was observed, while only a small decrease in free T3 was evident. Thyroxine binding globulin (TBG) concentration fell during propranolol treatment while thyroxine binding prealbumin (TBPA) concentration rose. The changes observed in the euthyroid state are consistent with inhibition of peripheral deiodination of T4 and rT3; an additional effect of propranolol on binding protein metabolism was evident.