Changes In Thyroid Hormone Concentrations Research Articles

Changes in thyroid hormone concentrations over time in dogs with autoimmune thyroiditis.

The objective of this study was to follow long-term changes in the concentration of thyroid hormones in dogs with subclinical thyroiditis. Samples were obtained from 125 dogs with subclinical thyroiditis. The study population included 70 female and 55 male dogs. The mean testing interval was 3.9 years from initial testing (SD, 2.3 years; range, 1 to 9 years). Dogs with subclinical thyroiditis were identified retrospectively using results from the Orthopedic Foundation for Animals Canine Thyroid Profile performed by the Endocrinology Section of the Michigan State University Veterinary Diagnostic Lab. Owners were invited to submit follow-up serum samples with their veterinarian along with a medical history form, including subsequent treatments. At the time of retesting, 30% of the dogs had progressed to hypothyroidism and/or were treated with thyroxine. Fifty percent maintained positive or equivocal thyroglobulin autoantibody (TgAA) results while remaining euthyroid. Fourteen percent of the dogs became TgAA negative and remained euthyroid. In 6% of the cases tested, proper medical histories were not available, and a final classification could not be determined. These results indicate that most dogs with elevated thyroglobulin autoantibodies either exhibit persistent autoimmune thyroiditis with continued risk of hypothyroidism or progress to hypothyroidism when monitored for more than 1 year. Thyroid function in dogs with subclinical thyroiditis should be monitored every 12 months or if there is change in the clinical presentation.

A comparison of medium-term heat acclimation by post-exercise hot water immersion or exercise in the heat: adaptations, overreaching, and thyroid hormones.

This research compared thermal and perceptual adaptations, endurance capacity, and overreaching markers in men after 3, 6, and 12 days of post-exercise hot water immersion (HWI) or exercise heat acclimation (EHA) with a temperate exercise control (CON), and examined thyroid hormones as a mechanism for the reduction in resting and exercising core temperature (Tre) after HWI. HWI involved a treadmill run at 65% V̇o2peak at 19°C followed by a 40°C bath. EHA and CON involved a work-matched treadmill run at 65% V̇o2peak at 33°C or 19°C, respectively. Compared with CON, resting mean body temperature (Tb), resting and end-exercise Tre, Tre at sweating onset, thermal sensation, and perceived exertion were lower and whole-body sweat rate (WBSR) was higher after 12 days of HWI (all P ≤ 0.049, resting Tb: CON -0.11 ± 0.15°C, HWI -0.41 ± 0.15°C). Moreover, resting Tb and Tre at sweating onset were lower after HWI than EHA (P ≤ 0.015, resting Tb: EHA -0.14 ± 0.14°C). No differences were identified between EHA and CON (P ≥ 0.157) except WBSR that was greater after EHA (P = 0.013). No differences were observed between interventions for endurance capacity or overreaching markers (mood, sleep, Stroop, P ≥ 0.190). Thermal adaptations observed after HWI were not related to changes in thyroid hormone concentrations (P ≥ 0.086). In conclusion, 12 days of post-exercise hot water immersion conferred more complete heat acclimation than exercise heat acclimation without increasing overreaching risk, and changes in thyroid hormones are not related to thermal adaptations after post-exercise hot water immersion.

Evidence of an olfactory imprinting window in embryonic Atlantic salmon

AbstractSalmonid olfactory imprinting during the parr‐to‐smolt transformation (PST) is essential for successful homing to natal spawning sites years later by mature fish. However, in many species, juveniles may move away from spawning sites before the PST, yet home to the natal site as adults, indicating that there may be multiple imprinting windows. To test the hypothesis that olfactory learning can occur prior to the PST, we exposed Atlantic salmon (Salmo salar) to the imprinting odorant L‐arginine at the alevin stage. Odour exposures were conducted in both brook and well water to test whether environmental characteristics of the rearing water affected endocrine and imprinting responses. Changes in thyroid hormone concentration differed over the course of development between water sources (p < .001). In brook water, fish experienced a plateau in thyroxine concentrations coinciding with the L‐arginine exposure, but a continued decline was observed in those kept in well water. In subsequent experiments, migratory stage adults from the brook water‐reared group exposed to L‐arginine spent significantly more time than control fish (p < .04) in the L‐arginine odour arm of a two‐choice maze, whereas the well water‐reared group's responses did not differ from those of the control group. Our findings provide physiological and behavioural evidence supporting the hypothesis that imprinting in Atlantic salmon can occur before the PST. These results indicate that the water source during development may affect the ability to imprint and may have implications for hatchery programmes that often incubate salmonids in well water during the alevin life stage.

Growth hormone replacement may influence the biological action of thyroid hormone on liver and bone tissue

ObjectiveGrowth hormone (GH) replacement alters the peripheral interconversion of thyroxine (T4) and triiodothyronine (T3). However, little is known about the clinical impact of these alterations. We aimed to compare changes observed in the serum T3:T4 ratio with known biological markers of thyroid hormone action derived from different peripheral tissues. DesignWe prospectively studied twenty GH deficient men before and after GH replacement in a tertiary referral endocrine center. Serum biochemical measurements included insulin like growth factor-1 (IGF-1), thyroid hormones (free & total T3, free & total T4 and reverse T3) and TSH. Changes in thyroid hormone concentration were compared to alterations in hepatic and bone biomarkers of thyroid hormone action. ResultsGH replacement provoked a decline in serum free T4 concentration (−1.09 ± 1.99 pmol/L; p = 0.02) and an increase in free T3 (+0.34 ± 0.15 pmol/L; p = 0.03); therefore, the free T3:free T4 ratio increased from 0.40 ± 0.02 to 0.47 ± 0.02 (p = 0.002). Sex hormone binding globulin (SHBG) level was unchanged. However, a decline in serum ferritin (−26.6 ± 8.5 ng/mL; p = 0.005) correlated with a fall in freeT4. Alterations in lipid profile, including a rise in large HDL sub-fractions and Lp (a) (+2.1 ± 21.1 nmol/L; p = 0.002) did not correlate with thyroid hormone levels. Significant increases were recorded in serum bone turnover markers - procollagen type 1 amino-terminal propeptide +57.4%; p = 0.0009, osteocalcin +48.6%; p = 0.0007; c-terminal telopeptides of type 1 collagen +73.7%; p = 0.002. Changes in bone formation markers occurred in parallel with fluctuations in thyroid hormone. ConclusionGH-induced alterations in the thyroid axis are associated with complex, tissue specific effects on thyroid hormone action. Modulation of bone turnover markers suggests that GH may improve the biological action of thyroid hormone on bone.

The effects of perinatal bisphenol A exposure on thyroid hormone homeostasis and glucose metabolism in the prefrontal cortex and hippocampus of rats.

IntroductionBisphenol A (BPA) is an endocrine disruptor widely used to manufacture consumer goods. Although the thyroid hormone (TH) disrupting potential of BPA has been thought to be responsible for the neuropsychiatric deficits in the animals that experienced perinatal BPA exposure, the TH availability change at the level of specific brain structures has not been subject to systematic investigation.MethodsIn the present study the impacts of perinatal BPA exposure (0.1 mg/L in drinking water) spanning gestation and lactation on TH homeostasis in the prefrontal cortex (PFC) and hippocampus were assessed in male Sprague–Dawley rats at postnatal day 21 (PND21) and PND90. As TH regulates brain glucose metabolism at multiple levels，the effects of BPA treatment on glucose metabolism in the brain tissues were also assessed in adult rats.ResultsThe results showed heterogeneous changes in TH concentration induced by BPA between serum and brain tissues, additionally, in the BPA–treated pups, up–regulated expression of the TH transporter monocarboxylate 8 mRNA at PND21 and increased type 3 iodothyronine deiodinase mRNA expressions at PND21 and PND90 were observed. Meanwhile, decreased glucose metabolism was seen in the PFC and hippocampus, while deficits in locomotor activity, spatial memory and social behaviors occurred in BPA‐treated groups.ConclusionThese data support the concept that the developing brain possesses potent mechanisms to compensate for a small reduction in serum TH, such as serum hypothyrodism induced by BPA exposure, however, the long‐term negative effect of BPA treatment on TH homeostasis and glucose metabolism may be attributable to neuropsychiatric deficits after mature.

Thyroid Hormone Disruption in the Fetal and Neonatal Rat: Predictive Hormone Measures and Bioindicators of Hormone Action in the Developing Cortex.

Adverse neurodevelopmental consequences remain a primary concern when evaluating the effects of thyroid hormone (TH) disrupting chemicals. Though the developing brain is a known target of TH insufficiency, the relationship between THs in the serum and the central nervous system is not well characterized. To address this issue, dose response experiments were performed in pregnant rats using the goitrogen propylthiouracil (PTU) (dose range 0.1-10 ppm). THs were quantified in the serum and brain of offspring at gestational day 20 (GD20) and postnatal day 14 (PN14), two developmental stages included in OECD and EPA regulatory guideline/guidance studies. From the dose response data, the quantitative relationships between THs in the serum and brain were determined. Next, targeted gene expression analyses were performed in the fetal and neonatal cortex to test the hypothesis that TH action in the developing brain is linked to changes in TH concentrations within the tissue. Results show a significant reduction of T4/T3 in the serum and brain of the GD20 fetus in response to low doses of PTU; interestingly, very few genes were significantly different at any dose tested. In the PN14 pup significant reductions of T4/T3 in the serum and brain were also detected; however, twelve transcriptional targets were identified in the neonatal cortex that correlated well with reduced brain THs. These results show that serum T4 is a good predictor of brain THs, and offer several target genes that could serve as pragmatic readouts of T4/T3 dysfunction within the PN14 cortex.

Alterations In Thyroid Hormone Levels Following Growth Hormone Replacement Exert Complex Biological Effects

Alterations in the thyroid axis are frequently observed following growth hormone (GH) replacement, but uncertainty exists regarding their clinical significance. We aimed to compare fluctuations in circulating thyroid hormone levels, induced by GH, to changes in sensitive biological markers of thyroid hormone action. This was a prospective observational clinical study. Twenty hypopituitary men were studied before and after GH replacement. Serum thyroid-stimulating hormone (TSH), thyroid hormones, and insulin-like growth factor 1 were measured. Changes in thyroid hormone concentrations were compared to alterations in resting metabolic rate and cardiac time intervals. Health-related quality of life (QOL) was assessed by disease-sensitive and generic questionnaires. Following GH replacement, free thyroxine concentration declined and free triiodothyronine level increased. Resting energy expenditure increased, particularly in subjects with profound hypopituitarism, including TSH deficiency (16.73 ± 1.75 kcal/kg/min vs. 17.96 ± 2.26 kcal/kg/min; P = .01). Alterations in the thyroid axis were more pronounced in subjects with a low/normal baseline respiratory quotient (RQ) who experienced a paradoxical rise in RQ (0.81 vs. 0.86; P = .01). Subjects with a high baseline RQ experienced a slight but nonsignificant fall in RQ without alteration in thyroid axis. The isovolumetric contraction time was shortened during the study; however, this did not reach statistical significance. Improvements in QOL were observed despite alterations in thyroid axis. Changes in the thyroid axis following GH replacement are associated with complex tissue-specific effects. These fluctuations may induce a hypothyroid phenotype in some tissues while appearing to improve the biological action of thyroid hormone in other organs. AGHDA = Assessment of Growth Hormone Deficiency in Adulthood; CHOox = carbohydrate oxidation; ET = ejection time; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; GHD = growth hormone deficiency; HB-RQ = high baseline respiratory quotient; HPT = hypothalamic-pituitary-thyroid; ICT = isovolumetric contraction time; IGF-1 = insulin-like growth factor 1; IRT = isovolumetric relaxation time; LB-RQ = low baseline respiratory quotient; LV = left ventricular; NHP = Nottingham Health Profile; QOL = quality of life; REE = resting energy expenditure; RQ = respiratory quotient; rT3 = reverse triiodothyronine; SF-36 = Short Form 36; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; TT3 = total triiodothyronine; TT4 = total thyroxine.

Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats.

Individuals who consume a diet deficient in zinc (Zn-deficient) develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH) levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH). PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood.

Changes in thyroid hormone concentrations during neonatal extracorporeal membrane oxygenation.

Thyroid hormone concentrations can be disturbed during critical illness. Our aim was to determine changes in thyroid hormone concentrations during neonatal extracorporeal membrane oxygenation (ECMO). We included 21 ECMO-treated neonates. Age-specific s.d. scores (SDS) of free and total thyroxine (FT4; TT4), reverse and total triiodothyronine (rT3; TT3), thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) were determined at six fixed time-points. Data were analyzed using general linear models. At baseline, mean SDS FT4 (-0.78, 95% CI: -1.37 to -0.19), TT4 (-1.97, 95% CI: -2.76 to -1.18), TT3 (-0.88, 95% CI: -1.13 to -0.63), TSH (-2.14, 95% CI: -2.93 to -1.35) and TBG (-3.52, 95% CI: -4.55 to -2.50) were low with high mean SDS rT3 (0.53, 95% CI: 0.28 to 0.78). One hour after start ECMO, TT4, TSH and TBG had further declined; 12 h after start ECMO TT3 had declined (all P<0.05). After this decline, mean SDS TSH increased to the baseline level 12 h after start ECMO (-2.50, 95% CI: -3.22 to -1.79), and was higher than baseline 48 h after start ECMO (-0.56, 95% CI: -1.29 to 0.17). This TSH increase was followed by increases in TT4 and TT3. FT4 remained constant within the normal range during ECMO. Thyroid hormone concentrations before ECMO were suggestive of non-thyroidal illness syndrome (NTIS). During ECMO, increases in TSH, TT4 and TT3 after an initial decline possibly reflect spontaneous restoration of the hypothalamic-pituitary-thyroid axis. FT4 remained constant within the normal range. This suggests that thyroxine therapy is not required during ECMO.

Thyroid hormones and cardiovascular disease.

Myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive to changes in the concentrations of circulating thyroid hormones. The importance of thyroid hormones in maintaining cardiovascular homeostasis can be deduced from clinical and experimental data showing that even subtle changes in thyroid hormone concentrations - such as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome - adversely influence the cardiovascular system. Some potential mechanisms linking the two conditions are dyslipidaemia, endothelial dysfunction, blood pressure changes, and direct effects of thyroid hormones on the myocardium. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Over the past 2 decades, accumulating evidence supports the association between abnormal thyroid function at the time of an acute myocardial infarction (MI) and subsequent adverse cardiovascular outcomes. Furthermore, experimental studies showed that thyroid hormones can have an important therapeutic role in reducing infarct size and improving myocardial function after acute MI. In this Review, we summarize the literature on thyroid function in cardiovascular diseases, both as a risk factor as well as in the setting of cardiovascular diseases such as heart failure or acute MI, and outline the effect of thyroid hormone replacement therapy for reducing the risk of cardiovascular disease.

Thyroxine in acute myocardial infarction (ThyrAMI) - levothyroxine in subclinical hypothyroidism post-acute myocardial infarction: study protocol for a randomised controlled trial.

BackgroundCardiac disease is the most common cause of morbidity and mortality in the United Kingdom. Even minor changes in thyroid hormone concentration may impact adversely on the cardiovascular system. Subclinical hypothyroidism (SCH) after admission for an acute cardiac problem has been associated with an increase in cardiac mortality and overall death. We have designed protocols for a prospective observational study to assess the association of thyroid function at the time of acute myocardial infarction (AMI) with cardiovascular outcomes, and a double-blinded randomised placebo-controlled trial of levothyroxine to evaluate its effect on LV function and vascular health.Methods/DesignThyrAMI 1: This will be a prospective longitudinal observational study of patients with AMI that will be followed for 24 months to study the association between thyroid status at the time of AMI (within 24 hours of diagnosis) with vascular outcomes.ThyrAMI 2: This will be a prospective double-blinded randomised placebo-controlled trial of levothyroxine of 12 months duration in patients with AMI and SCH.Setting: Patients will be recruited from five hospitals in the North East of England.Participants: One hundred patients with thyroid function tests within the subclinical hypothyroid range upon admission with an AMI and no previous history of thyroid disease.Intervention: Levothyroxine will be administered at a starting dose of 25 mcg once daily, which will be increased at intervals if needed to maintain a TSH level between 0.4 to 2.5 mU/L, versus a placebo.Randomisation: Participants will be randomized with a computerised randomisation algorithm, stratified by type of MI (NSTEMI versus STEMI), in a 1:1 ratio to levothyroxine therapy or placebo (as container or bottle numbers), starting within 21 (+/− 7) days of AMI.Blinding: Assignment to either the LT4 or placebo arm will be double-blinded.Outcomes: The outcome will be the effect of levothyroxine on ventricular function, endothelial function and blood coagulability and rheology.DiscussionThere is evidence to suggest that treatment of SCH can improve cardiovascular parameters. Therefore, ThyrAMI 1 and ThyrAMI 2 will be the first trials investigating SCH in AMI to give a better insight into whether thyroid hormone levels are a key target for improving cardiovascular outcomes.Trial registrationISRCTN number: ISRCTN52505169. Date of registration: 09/01/2015

Thyroid axis function after in-patient treatment of acute psychosis with antipsychotics: a naturalistic study.

BackgroundEndocrine function in psychiatric patients may be affected by mental disorder itself as well as by antipsychotic medications.The aim of this naturalistic observational study was to determine if treatment of acute psychotic episode with antipsychotic medication affects thyroid axis hormone concentrations and if such changes are associated with symptomatic improvement.MethodsEighty six adult acute psychotic patients, consecutively admitted to a mental hospital, were recruited for the study. All patients were physically healthy and without thyroid disease. During the hospitalization period all study patients received treatment with antipsychotic medication according to clinical need. Severity of the psychotic episode was evaluated using the Brief Psychiatric Rating Scale (BPRS) and venous blood samples were drawn for analysis of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) concentrations on the day of admission and on the day of discharge from the hospital.ResultsAntipsychotic drug treatment was associated with decrease of mean FT3 (p < 0.001) and FT4 (p = 0.002) concentrations; and with increase of mean TSH (p = 0.016) concentrations. Changes in thyroid hormone concentrations were mostly predicted by baseline hormone concentrations. Individual changes were not limited to decrease in high hormone concentrations; in patients who had low FT3 or FT4 concentrations, treatment resulted in increase in concentrations. Such an increase was established in one-quarter of patients for FT3 concentrations and in one-third of patients for FT4 concentrations. Fall in FT4 concentrations negatively correlated with the improvement in the BPRS score (r = −0.235, p = 0.023).ConclusionsThe study indicates that antipsychotic treatment resulted in a decrease in mean FT3 concentrations and in an increase in mean TSH concentrations after recovery from acute psychosis. Symptomatic improvement was less evident in patients who experienced a decrease in FT4 concentrations.Trial registrationEudraCT No.2007-001541-18

Course of hatch and developmental changes in thyroid hormone concentration in blood of chicken embryo following in ovo riboflavin supplementation

The influence of riboflavin on the function of the hypothalamo-pituitary-thyroid axis during chicken embryogenesis is poorly understood. Therefore, examination of the effects of in ovo riboflavin supplementation on the possible linkage between the thyroid gland function and chick embryonic development seems to be interesting. Eggs on the sixth day of incubation were injected with 0 (control), 60, or 600 µg of riboflavin/egg. Blood samples were collected on the 12th, 15th, 18th, and 20th days of embryogenesis. Thyroxine (T4) and triiodothyronine (T3) concentrations in plasma samples were determined by radioimmunoassay method. The time of external pipping and hatching of each chick as well as the body weights of sampled and newly hatched chicks were recorded. Generally, riboflavin supplied in ovo did not affect chicken embryo mortality and hatchability; however, a dose of 600 µg of riboflavin/egg had a tendency to reduce embryo body weight. Chicks exposed to 60 µg of riboflavin/egg hatched 3.7 h earlier in comparison with controls and were characterized by a higher synchronization degree of hatching. Both applied doses of riboflavin significantly elevated T4 concentrations in blood plasma of the chicken embryos; however, on day 20 of embryogenesis, both applied doses of riboflavin decreased T3 levels in blood circulation. The data presented here suggest that riboflavin supplementation at the early stages of embryogenesis markedly affects embryonic development and influences thyroid hormone metabolism during the second half of embryogenesis.

Thyroid hormone receptor β mediates thyroid hormone effects on bone remodeling and bone mass

Excess thyroid hormone (TH) in adults causes osteoporosis and increases fracture risk. However, the mechanisms by which TH affects bone turnover are not elucidated. In particular, the roles of thyroid hormone receptor (TR) isotypes in the mediation of TH effects on osteoblast-mediated bone formation and osteoclast-mediated bone resorption are not established. In this study we have induced experimental hypothyroidism or hyperthyroidism in adult wild-type, TRα- or TRβ-deficient mice and analyzed the effects of TH status on the structure and remodeling parameters of trabecular bone. In wild-type mice, excess TH decreased bone volume and mineralization. High TH concentrations were associated with a high bone-resorption activity, assessed by increased osteoclast surfaces and elevated concentrations of serum bone-resorption markers. Serum markers of bone formation also were higher in TH-treated mice. TRα deficiency did not prevent TH action on bone volume, bone mineralization, bone formation, or bone resorption. In contrast, TRβ deficiency blocked all the early effects of excess TH observed in wild-type mice. However, prolonged exposure to low or high TH concentrations of TRβ-deficient mice induced mild modifications of bone structure and remodeling parameters. Together our data suggest that TRβ receptors mediate the acute effects produced by transient changes of TH concentrations on bone remodeling, whereas TRα receptors mediate long-term effects of chronic alterations of TH metabolism. These data shed new light on the respective roles of TRs in the control of bone metabolism by TH.

The Nuclear Receptor Corepressor (NCoR) Controls Thyroid Hormone Sensitivity and the Set Point of the Hypothalamic-Pituitary-Thyroid Axis

The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T(4) and T(3) concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary-thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T(4) and T(3) and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by the serum TSH.

Effects of selenomethionine supplementation on selenium status and thyroid hormone concentrations in healthy adults

Background: Selenium, a potential cancer prevention agent currently being tested against prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), plays an integral role in thyroid metabolism. The effects of long-term selenium supplementation on thyroid hormone concentrations are unknown.Objective: The objective was to investigate the effects of long-term selenium supplementation on thyroid hormone concentrations.Design: Twenty-eight healthy adults took 200 μg selenomethionine/d for 28 mo. The thyroid hormones triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) were measured in plasma for 4 mo before supplementation and quarterly during supplementation. The assay methods were changed midstudy; the results of the 2 methods were not comparable. Therefore, one analysis was conducted based on the results of the first method, and a second analysis was based on all of the data, adjusted for the change. Serial data collection permitted a test for trends rather than simply a difference between initial and final values.Results: By 9 mo, mean (±SEM) plasma selenium concentrations had increased from 1.78 ± 0.07 μmol/L at baseline to 2.85 ± 0.11 μmol/L for men and from 1.64 ± 0.04 to 3.32 ± 0.1.2 μmol/L for women. T3 concentrations in men increased 5% per year (P = 0.01). T4 and TSH concentrations were unchanged.Conclusions: Selenium supplementation produced no clinically significant changes in thyroid hormone concentrations. A small but statistically significant increase in T3 concentrations was noted in men, with no corresponding decreases in TSH. A subset of SELECT subjects might be monitored periodically for changes during long-term selenium supplementation.

Enhancement of Vascular Endothelial Function by Recombinant Human Thyrotropin

The cardiovascular consequences of thyroid diseases are attributed to the altered secretion of thyroid hormones. The possibility that TSH also affects the cardiovascular system has been poorly explored. Endothelial cells and vascular smooth muscle cells possess TSH receptors. The study was designed to determine whether TSH exerts any effect on vascular homeostasis. Two different double-blind, controlled studies were performed, one in eight healthy volunteers and the other in six thyroidectomized patients. Recombinant human (rh) TSH (or saline) was infused intrabrachially (1 mU/min) to raise TSH to severe hypothyroidism levels (approximately 100 microU/ml). Endothelium-dependent and -independent vasodilation was tested by intraarterial infusion of acetylcholine and sodium nitroprusside, respectively, and forearm blood flow was measured by plethysmography. Endothelium-dependent vasodilation was potentiated by rhTSH (P < 0.05 for the treatment effect; general linear model). The dynamics of the response was also profoundly affected by rhTSH because the dose-response curve was much steeper than in controls (P < 0.02 for the interaction between TSH and acetylcholine). rhTSH had no effect on endothelium-independent vasodilation (P = NS for both treatment and interaction). During rhTSH infusion, free T(3) levels increased slowly from 2.3 +/- 0.2 to 3.6 +/- 0.2 pg/ml. In thyroidectomized patients, rhTSH potentiated endothelium-mediated vasodilation to an extent similar to that of healthy subjects (P = 0.05 for the treatment effect and P = 0.01 for the interaction), without affecting the response to nitroprusside. In these patients, thyroid hormones remained unchanged during rhTSH infusion. rhTSH exerts marked effects on the resistance vessels by enhancing endothelial-mediated vasodilation, independent of changes in thyroid hormone concentration.

Effect of Graves’ Disease and Methimazole on Warfarin Anticoagulation

To describe a case of Graves' disease treated with methimazole and examine the influence of thyroid hormone alteration on warfarin anticoagulation. A 54-year-old man presented to the emergency department with palpitations, fatigue, weight loss, and anxiety attacks. He was taking no medications at that time. An electrocardiogram showed new onset atrial fibrillation. His thyroid profile was consistent with hyperthyroidism. The patient was admitted to the intensive care unit and started on methimazole 30 mg/day, metoprolol, enoxaparin, and warfarin 5 mg/day. Postdischarge doses of warfarin and methimazole were adjusted over the next several months based on thyroid panel results indicative of hypothyroidism. Postdischarge changes in methimazole dose caused alterations in thyroid function and intensity of anticoagulation as measured by international normalized ratio. Interactions between warfarin and drugs that alter thyroid hormone concentrations have been reported; however, the extent and significance of the interaction between methimazole and warfarin have been inadequately described. Thyroid hormone concentrations influence the metabolic rates of proteins and, thus, can alter the amount of vitamin K-dependent clotting factors, which in turn can alter the extent of inhibition by warfarin. This may lead to changes in the intensity of anticoagulation and thereby increase the risk of thromboembolic or hemorrhagic events. Changes in thyroid hormone concentrations have the potential to significantly alter the extent of warfarin-induced anticoagulation. Clinicians must be aware of the need for close anticoagulation monitoring and dosage adjustment in patients receiving concomitant warfarin and methimazole. The full extent of this interaction may be delayed following a change in methimazole dose.

The effects of age, season and geographic region on thyroid hormones in Steller sea lions ( Eumetopias jubatus)

The purpose of this study was to investigate thyroid hormone concentrations, thyroxine (T 4) and triiodothyronine (T 3), in order to determine basal levels in Steller sea lions of different ages and over seasons. Serum concentrations of total T 4 were highest in Steller sea lions followed by total T 3 concentrations. Concentrations of free T 4 and free T 3 were three to four orders of magnitude lower. Concentrations for all four thyroid hormone measurements tended to a lower level as animals matured beyond the neonatal stage. When thyroid hormones from captive sea lions were evaluated across seasons, all thyroid hormones were highest in the July to September period. When compared across the geographic range, animals in southeast Alaska tended to have lower thyroid hormone levels, while the Steller sea lions west of Prince William Sound and animals from the Russian Far East had significantly higher concentrations. Significant inter-annual differences in concentrations were also observed across the geographic range. With an understanding of the basic changes in thyroid hormone concentrations, changes in plane of nutrition or life history states (i.e. fasting, pregnancy or lactation) can now be evaluated for their effect on the overall health of this endangered species.

Thyroid Function Testing in Pregnancy and Thyroid Disease

During pregnancy the thyroid is hyperstimulated, resulting in changes in thyroid hormone concentrations. Accurate assessment of thyroid function during pregnancy is critical, for both the initiation of thyroid hormone therapy, and for the adjustment of thyroid hormone dose in those already receiving thyroid hormone. Trimester-specific intervals are especially important during pregnancy when thyroid insufficiency may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits. Gestational age-specific reference intervals are now available for thyroid function tests. Knowing the expected normal changes in hormone concentrations throughout pregnancy allows individualized supplementation when necessary.