Circulating Thyroid Hormone Research Articles

The 5′-Deiodinases Are Not Essential for the Fasting-Induced Decrease in Circulating Thyroid Hormone Levels in Male Mice: Possible Roles for the Type 3 Deiodinase and Tissue Sequestration of Hormone

Fasting in rodents is characterized by decreases in serum T4 and T3 levels but no compensatory increase in serum TSH level. The types 1 and 2 deiodinases (D1 and D2) are postulated to play key roles in mediating these changes. However, serum T4 and T3 levels in fasted 5'-deiodinase-deficient mice decreased by at least the same percentage as that observed in wild-type mice, whereas serum TSH level was unaffected. D3 activity was increased in kidney, muscle, and liver up to 4-fold during fasting, and the mean serum rT3 level was increased 3-fold in fasted D1-deficient mice, compared with fed animals. In wild-type mice, the tissue contents of T4 and T3 in liver, kidney, and muscle were unchanged or increased in fasted animals, and after the administration of [(125)I]T4 or [(125)I]T3, the radioactive content in the majority of tissues from fasted mice was increased 2- or 4-fold, respectively. These findings suggest that the observed fasting-induced reductions in the circulating T3 and T4 levels are mediated in part by increased D3 activity and by the sequestration of thyroid hormone and their metabolites in tissues. Studies performed in D3-deficient mice demonstrating a blunting of the fasting-induced decrease in serum T4 and T3 levels were consistent with this thesis. Thus, the systemic changes in thyroid hormone economy as a result of acute food deprivation are not dependent on the D1 or D2 but are mediated in part by sequestration of T4 and T3 in tissues and their enhanced metabolism by the D3.

Therapeutic Plasmapheresis in Preparation of Toxic Multinodular Goiter for Surgery

Thyrotoxicosis is a condition characterized by excessive amounts of thyroid hormones in bloodstream leading to multisystem involvement with a high mortality rate (1,2). Antithyroid drugs, radioactive iodine and thyroidectomy are three conventional forms of treatment selected according to the specific cause of hyperthyroidism. Thyroidectomy is the definitive treatment especially in patients resistant to other treatment options. Surgical intervention should be performed when the patient is euthyroid to decrease perioperative cardiac risks (3). Plasmapheresis is a medical procedure that removes the thyroid hormones and antibodies from the bloodstream of patients who are in need of urgent surgical intervention. It has been utilized for the treatment of several immunologic and nonimmunologic disorders such as Graves’ disease, intoxication of levothyroxin and amiodarone (4,5). Here, we report the case of a patient with toxic multinodular goiter (TMNG) who was prepared for surgery by plasmapheresis due to the side effects of antithyroid drugs. In the literature, there are many cases of hyperthyroidism diagnosed as Graves’ disease treated with plasmapheresis for the removal of circulating thyroid hormones. However, the role of plasmapheresis in the treatment of TMNG is not fully determined.

PBDE flame retardants

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardant chemicals that have been used in large quantities and are now detected worldwide in humans and wildlife. To complement reviews of effects on human health, this review discusses and synthesizes current evidence of PBDE toxicokinetics and toxicity mechanisms leading to perturbations of thyroid hormone homeostasis in fish. PBDE disruptions to thyroid signaling in fish appear to proceed through multiple pathways involving declines in circulating thyroid hormones, disrupted deiodination activity, hindered hormone transport, and altered transcriptional regulation of genes involved in thyroid hormone production, transport, and genomic signaling. PBDE exposures have also been linked to impacts on reproductive health with reductions in fecundity, spawning, hatching success, and offspring survival observed in some species, as well as impaired fertility. These studies on PBDE mediated hormone disruption in fish can help inform future st...

Loss of Acquired Functions Due to Thyroid Function Disorder in a Patient with Spinal Cord Injury

The metabolic responses to spinal cord injury (SCI) involve every organ and tissue of the body and yet, surprisingly, little is known about the underlying mechanisms. Many factors are known to affect levels of circulating thyroid hormones such as activity level, nutritional status, systemic illness, drugs, age and trauma. Even healthy person requisited to the bedrest, the normal circadian variation in T3 and T4 may be disappeared. So any condition of traumatic stress will be associated with changes in serum thyroid hormone levels that have been referred to as several syndromes. During chronic disease processes, the state of stress results in hypermetabolism, increased energy expenditure, hyperglycemia and muscle loss. It is anticipated that appropriate metabolic support could improve the outcome in these patients, but considerable controversy remains regarding the indicated therapeutic approach. In patients with SCI, regression or loss of existing functions can be monitored in patients in frequently developed situations due to metabolic problems such as heterotopic ossification, urinary tract infections, deep vein thrombosis, pressure ulcers, neuropathic pain, psychological problems and thyroid dysfunction. In this report we present a chronic SCI patient admitted to the clinic with the chief complaint of loss of the functional status who was diagnosed as a thyroid dysfunction.

Iridoid glucoside attenuates hyperglycemia-mediated oxidative stress and thyroid hormone function in streptozotocin–induced diabetic rats

The present study was to evaluate the effect of iridoid glucoside on the levels of blood glucose, plasma insulin, serum total protein, albumin, thyroid hormone (T3, T4), TSH, LPO and activities of both enzymic and non-enzymic antioxidants in streptozocin-induced diabetic rats. The levels of blood glucose, TBARS and hydroperoxide were significantly increased whereas the levels of plasma insulin and activities of enzymic antioxidants (SOD, CAT, GPx and GST) and the levels of non-enzymic antioxidants (vitamin C, vitamin E) and reduced glutathione were decreased in the liver and kidney tissues of diabetic rats. In addition, serum levels of total protein, albumin, T3, T4 and TSH were also decreased in diabetic rats when compared to control rats. Oral administration of iridoid glucoside to diabetic rats showed significant ameliorative effects on all the biochemical parameters studied. Moreover, the iridoid glucoside showed free radical scavenging activity assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro which may have responsible for these hypoglycemic and improved antioxidant statuses in vivo. The effect produced by iridoid glucoside on various parameters was comparable to that of glibenclamide. These results indicated that iridoid glucoside possesses antidiabetic and antioxidant potential in addition to synthesis and/or secretion of circulating thyroid hormone.

Rapid method for the measurement of circulating thyroid hormones in low volumes of teleost fish plasma by LC-ESI/MS/MS

Thyroid hormones are critical regulators of normal development and physiological functioning in all vertebrates. Radioimmunoassay (RIA) approaches have been the method of choice for measuring circulating levels of thyroid hormones in vertebrates. While sensitive, RIA-based approaches only allow for a single analyte measurement per assay, can lack concordance across platforms and laboratories, and can be prone to analytical interferences especially when used with fish plasma. Ongoing advances in liquid chromatography tandem mass spectrometry (LC/MS/MS) have led to substantial decreases in detection limits for thyroid hormones and other biomolecules in complex matrices, including human plasma. Despite these advances, current analytical approaches do not allow for the measurement of native thyroid hormone in teleost fish plasma by mass spectrometry and continue to rely on immunoassay. In this study, we developed a new method that allows for the rapid extraction and simultaneous measurement of total T4 (TT4) and total T3 (TT3) in low volumes (50μL) of fish plasma by LC/MS/MS. Methods were optimized initially in plasma from rainbow trout (Oncorhynchus mykiss) and applied to plasma from other teleost fishes, including fathead minnows (Pimephales promelas), mummichogs (Fundulus heteroclitus), sockeye salmon (Oncorhynchus nerka), and coho salmon (Oncorhynchus kisutch). Validation of method performance with T4- and T3-spiked rainbow trout plasma at 2 and 4ng/mL produced mean recoveries ranging from 82 to 95% and 97 to 105%, respectively. Recovery of (13)C12-T4 internal standard in plasma extractions was: 99 ± 1.8% in rainbow trout, 85 ± 11% in fathead minnow, 73 ± 5.0% in mummichog, 73 ± 1.7% in sockeye salmon, and 80 ± 8.4% in coho salmon. While absolute levels of thyroid hormones measured in identical plasma samples by LC/MS/MS and RIA varied depending on the assay used, T4/T3 ratios were generally consistent across both techniques. Less variability was measured among samples subjected to LC/MS/MS suggesting a more precise estimate of thyroid hormone homeostasis in the species targeted. Overall, a sensitive and reproducible method was established that takes advantage of LC/MS/MS techniques to rapidly measure TT4 and TT3 with negligible interferences in low volumes of plasma across a variety of teleost fishes.

Supraphysiologic Doses of Levothyroxine as Adjunctive Therapy in Bipolar Depression

Suboptimal availability of circulating thyroid hormones may contribute to the high rate of treatment failures in bipolar disorder. This study tested the efficacy of adjunctive treatment with supraphysiologic doses of levothyroxine in patients with bipolar depression and the hypothesis that women would display a better outcome compared to men. The aims of this multicenter, 6-week, double-blind, randomized, placebo-controlled fixed-dose (300 μg/d) trial conducted from 2004 to 2009 were to assess efficacy and tolerability of levothyroxine adjunctive to continuing treatment with mood stabilizer and/or antidepressant medication for patients with bipolar I or II disorder, currently depressed (DSM-IV), and to investigate gender differences in treatment response. The primary efficacy variable was mean change in Hamilton Depression Rating Scale (HDRS) score. Of 74 patients enrolled in the study, 62 (35 with bipolar I; mean age = 44.9 years) were randomized. Mean change in HDRS score from randomization to week 6 was larger in the levothyroxine group compared to the placebo group, with a 2.7-point difference (decline of -7.8 [38.3%] vs -5.1 [25.5%]; last-observation-carried-forward analysis). The course of HDRS scores over time from randomization to week 6 was significantly different between groups at week 4 (P = .046) but not at the end of the placebo-controlled phase (P = .198). The secondary analysis of women (n = 32) revealed a significant difference between groups in mean change in HDRS score (-16.6% placebo vs -42.4% levothyroxine, P = .018). A mixed-effects model for repeated-measures analysis showed a significant between-group difference in HDRS score (6.8, P = .012) for women. High thyroid-stimulating hormone levels, indicating suboptimal levels of circulating thyroid hormones, were predictive for positive treatment outcome in women treated with levothyroxine in a linear regression model (F3 = 3.47; P = .05). This trial demonstrated that patients treated with levothyroxine did numerically better than those treated with placebo; however, the study failed to detect a statistically significant difference between the 2 groups in the primary outcome measure due to a high placebo response rate. Previous findings that women show better improvement in depression scores with levothyroxine compared to men were confirmed. ClinicalTrials.gov identifier: NCT01528839.

Fibromyalgia, Thyroid Dysfunction and Treatment Modalities

Fibromyalgia is a debilitating condition presenting with symptoms of chronic muscular pain, fatigue, insomnia and cognitive dysfunction among other symptoms, which lead to a diminished quality of life. Although the exact pathogenesis and underlying mechanisms which lead to clinical manifestation are unknown, there is a growing line of evidence suggesting an association between fibromyalgia and thyroid dysfunction. Numerous studies have reported that patients with fibromyalgia have a high incidence of hypothyroidism. Further, thyroid autoimmunity has also been associated with fibromyalgia symptom severity. Circulating thyroid hormones do not provide an accurate status of thyroid function in patients with fibromyalgia, rather intracellular thyroid hormone levels are more relevant. Low levels of intracellular hormones may result from mitochondrial dysfunction as active transport of hormones across cellular membranes is required. It is well known that mitochondrial dysfunction is associated with fibromyalgia. In order to correct thyroid dysfunction and manage symptoms presenting in fibromyalgia patients, a multi-disciplinary approach should be taken incorporating dietary supplements, nutraceuticals, dietary changes and complementary alternative therapies.

Jaundice and factor VII deficiency in newborn

Resistance to thyroid hormone is an uncommon condition. We report the clinical and laboratory findings of a case with both resistance to thyroid hormone and, a reduced capacity to produce and respond to thyroid hormone. RTH is a disorder characterized by elevated circulating thyroid hormones, state of non-suppressed pituitary TSH secretion and refractoriness to hormone action in peripheral tissues. Resistance to thyroid hormone might be an important additional diagnosis to consider in cases where thyrotropin remains persistently elevated. In this article we described an infant with RTH; her situation was diagnosed incidentally at birth with impaired hypothyroidism screening tests.

Growth and Development in a incidentally diagnosed Resistance to Thyroid Hormone

Resistance to thyroid hormone is an uncommon condition. We report the clinical and laboratory findings of a case with both resistance to thyroid hormone and, a reduced capacity to produce and respond to thyroid hormone. RTH is a disorder characterized by elevated circulating thyroid hormones, state of non-suppressed pituitary TSH secretion and refractoriness to hormone action in peripheral tissues. Resistance to thyroid hormone might be an important additional diagnosis to consider in cases where thyrotropin remains persistently elevated. In this article we described an infant with RTH; her situation was diagnosed incidentally at birth with impaired hypothyroidism screening tests.

They live in the land down under: thyroid function and basal metabolic rate in the Blind Mole Rat, Spalax

The Israeli blind subterranean mole rat (Spalax ehrenbergi superspecies) lives in sealed underground burrows under extreme, hypoxic conditions. The four Israeli Spalax allospecies have adapted to different climates, the cool–humid (Spalax galili, 2 n = 52 chromosomes), semihumid (S. golani, 2 n = 54) north regions, warm–humid (S. carmeli, 2 n = 58) central region and the warm–dry S. judaei, 2 n = 60) southern regions. A dramatic interspecies decline in basal metabolic rate (BMR) from north to south, even after years of captivity, indicates a genetic basis for this BMR trait. We examined the possibility that the genetically-conditioned interspecies BMR difference was expressed via circulating thyroid hormone. An unexpected north to south increase in serum free thyroxine (FT4) and total 3, 5, 3′-triiodo-L-thyronine (T3) (p < 0.02) correlated negatively with previously published BMR measurements. The increases in serum FT4 and T3 were symmetrical, so that the T3:FT4 ratio – interpretable as an index of conversion of T4 to T3 in nonthyroidal tissues – did not support relative decrease in production of T3 as a contributor to BMR. Increased north-to-south serum FT4 and T3 levels also correlated negatively with hemoglobin/hematocrit. North-to-south adaptations in spalacids include decreased BMR and hematocrit/hemoglobin in the face of increasing thyroid hormone levels, arguing for independent control of hormone secretion and BMR/hematocrit/hemoglobin. But the significant inverse relationship between thyroid hormone levels and BMR/hematocrit/hemoglobin is also consistent with a degree of cellular resistance to thyroid hormone action that protects against hormone-induced increase in oxygen consumption in a hostile, hypoxic environment.

Associations between single nucleotide polymorphisms in thyroid hormone transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones

BackgroundThyroid hormone (TH) action takes place intracellularly; therefore, transport across the plasma membrane by specific TH transporters, such as MCT8, MCT10 and OATP1C1, is necessary. Several single nucleotide polymorphisms (SNPs) in these genes were reported to be associated with TH concentrations; however, results have been inconsistent. MethodsSix SNPs in TH transporter genes (rs5937843-G/T and rs6647476-T/C in MCT8, rs14399-C/A in MCT10, rs10444412-C/T, rs10770704-C/T and rs36010656-C/A in OATP1C1) were genotyped in 2 cohorts; one consisting of 2416 men and women aged 35–55yrs (Asklepios), and the other of 941 men aged 25–45yrs (Siblos), using KASPar technology. TSH, FT3, FT4 and total T3 were determined by immuno-electrochemiluminescence in both cohorts; in the second cohort additional determination of total T4 by electrochemiluminescence and of reverse T3 (rT3) and thyroid binding globulin (TBG) by radioimmunoassays was performed. ResultsThe first SNP in MCT8 (rs5937843-G/T) was inversely associated with FT4 concentrations in men but not in women. In Siblos, this SNP showed also negative associations with TT4 and rT3; in men from Asklepios a trend for positive association with TSH was observed. The second SNP in MCT8 (rs6647476-T/C) was negatively associated with FT3 levels in men from the Siblos and the Asklepios cohort. In addition, an inverse association with TT3 levels in men from the Siblos was observed. Rs36010656 (C/A) in OATP1C1 was not in Hardy–Weinberg equilibrium and therefore excluded from further analyses. The other 2 SNPs in OATP1C1 (rs10444412-C/T and rs10770704-C/T) and the SNP in MCT10 (rs14399-C/A) were not related to TH levels in either cohort. ConclusionTwo SNPs in MCT8 were related to circulating thyroid hormone levels in men but not in women: the rs5937843 polymorphism (G/T) was inversely associated with FT4 levels and the rs6647476 (T/C) polymorphism related negatively to circulating FT3.

Total Laryngeal Transplant Explanted in 2012: 14 Years of Lessons Learned

Objectives: In 1998, the first successful total laryngeal transplant was performed at the Cleveland Clinic. The patient was a 40 year-old-man who had suffered an MVA, which left him aphonic. Not only was his larynx completely replaced with a vascularized graft, but also his pharynx, thyroid, parathyroids, and a portion of his trachea. Over the subsequent 14 years, much was learned about tolerance of a transplanted laryngeal complex, marking this surgery as the longest surviving maiden transplanted organ system when immunosuppression was applied. Methods: Outstanding voice quality and swallowing function were achieved, although volitional vocal cord movement was not attempted, and therefore the patient remained stoma dependent for breathing. The scientific advancement of understanding around laryngeal transplantation was concurrently conducted in the laboratory via animal models, which translated into gradual reduction in the level of immunosuppression for the patient without acute rejection. Results: After approximately a decade, a slowly progressive, chronic rejection process gradually rendered the organ non-functional, and the patient and his providers deemed him appropriate for explantation with free-flap reconstruction and tracheoesophageal puncture voice restoration. Pre-operative functional studies showed a reversion back to his original thyroidal tissue as the source of his circulating thyroid hormone. Post-explantation histologic studies demonstrated loss of tissue cellularity and organ architecture. Conclusions: On routine explantation follow-up, the patient was found to have an asymptomatic early stage, human papillomavirus-related oropharyngeal neoplasm that was successfully treated with surgical resection alone. Voice results will be demonstrated over the patient’s 14 year experience, as well as his own perspective on this landmark experience.

Associations between thyroid hormones and serum metabolite profiles in an euthyroid population.

The aim was to characterise associations between circulating thyroid hormones—free thyroxine (FT4) and thyrotropin (TSH)—and the metabolite profiles in serum samples from participants of the German population-based KORA F4 study. Analyses were based on the metabolite profile of 1463 euthyroid subjects. In serum samples, obtained after overnight fasting (≥8), 151 different metabolites were quantified in a targeted approach including amino acids, acylcarnitines (ACs), and phosphatidylcholines (PCs). Associations between metabolites and thyroid hormone concentrations were analysed using adjusted linear regression models. To draw conclusions on thyroid hormone related pathways, intra-class metabolite ratios were additionally explored. We discovered 154 significant associations (Bonferroni p < 1.75 × 10−04) between FT4 and various metabolites and metabolite ratios belonging to AC and PC groups. Significant associations with TSH were lacking. High FT4 levels were associated with increased concentrations of many ACs and various sums of ACs of different chain length, and the ratio of C2 by C0. The inverse associations observed between FT4 and many serum PCs reflected the general decrease in PC concentrations. Similar results were found in subgroup analyses, e.g., in weight-stable subjects or in obese subjects. Further, results were independent of different parameters for liver or kidney function, or inflammation, which supports the notion of an independent FT4 effect. In fasting euthyroid adults, higher serum FT4 levels are associated with increased serum AC concentrations and an increased ratio of C2 by C0 which is indicative of an overall enhanced fatty acyl mitochondrial transport and β-oxidation of fatty acids.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-013-0563-4) contains supplementary material, which is available to authorized users.

Thyroid Hormone Levels Within Reference Range Are Associated with Heart Rate, Cardiac Structure, and Function in Middle-Aged Men and Women

Triiodothyronine (T3) has many effects on the heart, and marked changes in cardiac function and structure occur in patients with (subclinical) thyroid disease. We investigated whether between-subject variation in thyroid hormone levels within the euthyroid range is also associated with heart rate and echocardiographic heart function and structure. Subjects were selected from the Asklepios study (n=2524), a population-representative random sample of patients aged between 35 and 55 years, free from overt cardiovascular disease at baseline. Analyses were restricted to 2078 subjects (1013 women and 1065 men), not using antihypertensive or thyroid medication nor having antithyroperoxidase antibody levels above clinical cut-off or thyrotropin (TSH) levels outside the reference range. All subjects were phenotyped in-depth and underwent comprehensive echocardiography, including diastolic evaluation. Thyroid function parameters were determined by automated electrochemiluminescence. Heart rate was robustly positively associated with (quartiles of) free T3 (FT3) and T3, both in subjects with TSH levels within reference (0.27-4.2 μU/L) and in narrow TSH range (0.5-2.5 μU/L; p<0.0001). FT3 and T3 were negatively associated with left ventricular (LV) end-diastolic volume but positively associated with relative wall thickness. Total T3 (TT3) was associated with enhanced ventricular contraction (as assessed by tissue Doppler imaging). Free thyroxine, FT3, and TT3 were positively associated with late ventricular filling, and TT3 was associated with early ventricular filling. We have demonstrated a strong positive association between thyroid hormone levels within the euthyroid range and heart rate, and more subtle effects on cardiac function and structure. More specifically, we suggest a smaller LV cavity size (with increased relative wall thickness), an enhanced atrial and ventricular contraction, and LV relaxation with higher circulating thyroid hormones. These results illustrate that variation in thyroid hormone levels, even within the reference range, exerts effects on the heart.

Quantification of Total Thyroxine in Plasma from Xenopus laevis

There is evidence that the endocrine systems of certain fish and wildlife can be affected by chemical contaminants, possibly resulting in developmental and reproductive problems. Perturbations in the hypothalamus-pituitary-thyroid (HPT) axis, in particular, can be detrimental during early development. Because the rate of amphibian metamorphosis is controlled by circulating thyroid hormones, tadpoles undergoing metamorphosis have been selected as relevant test organisms for evaluating the potential effects of a substance on the HPT axis in vertebrates. An indicative measure of HPT functioning in these assays is the concentration of the thyroid hormone, thyroxine (T4), in frog plasma. Therefore, there is a need for a validated method to measure T4 in plasma during amphibian metamorphosis. This study describes a method involving mixed-mode strong cation exchange solid-phase extraction (SPE) with ultrahigh-performance liquid chromatography and isotope dilution tandem mass spectrometry (UPLC-ID-MS-MS) to quantify total T4 in a small volume (10 µL) of plasma from Xenopus laevis (African clawed frog). The SPE procedure, together with MS detection, produced the required selectivity for the analysis of both T4 and the T4 internal standard. The limit of detection of the method was determined to be 0.2 ng/mL, whereas the lower limit of quantification was 0.5 ng/mL. The intra-day and inter-day precision values were less than ± 5 and ±10%, respectively. Concentrations of total T4 in the plasma of X. laevis tadpoles at metamorphic peak were calculated to be 10.7 ± 0.8 ng/mL, which is comparable to the results from radioimmunoassay. This validated UPLC-ID-MS-MS method for the determination of total T4 in plasma has demonstrated good accuracy and precision, with low susceptibility to interferences with the utilization of multiple reaction monitoring and ID.

Thyroid hormones correlate with resting metabolic rate, not daily energy expenditure, in two charadriiform seabirds

SummaryThyroid hormones affect in vitro metabolic intensity, increase basal metabolic rate (BMR) in the lab, and are sometimes correlated with basal and/or resting metabolic rate (RMR) in a field environment. Given the difficulty of measuring metabolic rate in the field—and the likelihood that capture and long-term restraint necessary to measure metabolic rate in the field jeopardizes other measurements—we examined the possibility that circulating thyroid hormone levels were correlated with RMR in two free-ranging bird species with high levels of energy expenditure (the black-legged kittiwake, Rissa tridactyla, and thick-billed murre, Uria lomvia). Because BMR and daily energy expenditure (DEE) are purported to be linked, we also tested for a correlation between thyroid hormones and DEE. We examined the relationships between free and bound levels of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) with DEE and with 4-hour long measurements of post-absorptive and thermoneutral resting metabolism (resting metabolic rate; RMR). RMR but not DEE increased with T3 in both species; both metabolic rates were independent of T4. T3 and T4 were not correlated with one another. DEE correlated with body mass in kittiwakes but not in murres, presumably owing to the larger coefficient of variation in body mass during chick rearing for the more sexually dimorphic kittiwakes. We suggest T3 provides a good proxy for resting metabolism but not DEE in these seabird species.

Does thyroid disruption contribute to the developmental neurotoxicity of chlorpyrifos?

Although organophosphate pesticides are not usually characterized as “endocrine disruptors,” recent work points to potential, long-term reductions of circulating thyroid hormones after developmental exposures to chlorpyrifos that are devoid of observable toxicity. We administered chlorpyrifos to developing rats on gestational days 17–20 or postnatal days 1–4, regimens that produce distinctly different, sex-selective effects on neurobehavioral performance. The prenatal regimen produced a small, but statistically significant reduction in brain thyroxine levels from juvenile stages through adulthood; in contrast, postnatal exposure produced a transient elevation in young adulthood. However, in neither case did we observe the sex-selectivity noted earlier for neurobehavioral outcomes of these specific treatment regimens, or as reported earlier for effects on serum T4 in developing mice. Thus, although chlorpyrifos has the potential to disrupt thyroid status sufficiently to alter brain thyroid hormone levels, the effect is small, and any potential contribution to neurobehavioral abnormalities remains to be proven.

The results of therapeutic plasma exchange in patients with severe hyperthyroidism: A retrospective multicenter study

Hyperthyroidism characterized by elevated serum levels of circulating thyroid hormones. The aim of hyperthyroidism treatment is to achieve a euthyroid state as soon as possible and to maintain euthyroid status. However, drug withdrawal and utilization of alternative therapies are needed in cases in which leucopenia or impairment in liver functions is observed during medical therapy. In the present study, we aimed to present our cases which underwent therapeutic plasma exchange (TPE) due to severe hyperthyroidism. The results of 22 patients who underwent therapeutic plasma exchange due to hyperthyroidism in Apheresis Units of Erciyes University and Gaziantep University, between 2006 and 2012, were retrospectively reviewed. These cases had severe thyrotoxic values despite anti-thyroid drug use. After TPE, we observed a significant decrease in free thyroxin (FT4) (p<0.001) and free triiodotyhronin (FT3) (p<0.004) levels. There was statistically significant increase in the mean values of TSH levels after TPE (p<0.001).Clinical improvement was achieved in hyperthyroidism by TPE in 20 cases (91%). Both FT3 and FT4 levels remained above the normal limits in two of 22 patients. TPE should be considered as an effective and safe therapeutic option to achieve euthyroid state before surgery or radioactive iodine treatment. TPE is a useful option in cases with severe hyperthyroidism unresponsive to anti-thyroid agents and in those with clinical manifestations of cardiac failure and in patients with severe adverse events during anti-thyroid therapy.

Thyroid dysfunction in the elderly

Thyroid dysfunction is common in the general population, and mild or subclinical forms can be present in more than 10% of individuals aged >80 years. The diagnosis of abnormal thyroid hormone concentrations in people aged >60 years poses a challenge, as the clinical presentation of thyroid dysfunction is usually nonspecific, and ageing is associated with a number of physiological changes that can affect thyroid function test results. Furthermore, the presence of acute or chronic nonthyroidal illnesses and the use of medications that interfere with thyroid function tests are common confounders in the determination of thyroid status in the elderly. Early diagnosis and treatment of overt thyroid dysfunction is crucial in this population in view of the marked effects of abnormal circulating thyroid hormone levels on a number of organ systems, including the heart, the skeleton and the neurological system. The clinical significance of mild thyroid overactivity and underactivity remains uncertain, and the need for treatment of subclinical thyroid dysfunction is much debated. A number of large epidemiological studies have identified associations between mild thyroid dysfunction and short-term as well as long-term adverse outcomes, and a small but increasing number of randomized controlled intervention studies have been reported. Guidelines recommend treatment of thyroid dysfunction on the basis of the degree of abnormal serum TSH concentrations, patient age and associated comorbidities. This Review describes the current evidence on the prevalence, diagnosis, management and long-term consequences of thyroid dysfunction in the elderly.