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This trial compared two thyrotropin-stimulation methods and two 131I doses for postoperative ablation in patients with low-risk thyroid cancer. Rates of ablation were similar in all treatment groups. Doses lower than those currently recommended may be adequate for this condition. Radioiodine ( 131 i) is administered to patients with thyroid cancer after total thyroidectomy for three reasons 1 – 3 : first, to eradicate normal-thyroid remnants (ablation) in order to achieve an undetectable serum thyroglobulin level; second, to irradiate any neoplastic focus in order to decrease the risk of recurrence; and third, to perform 131 I total-body scanning for persistent carcinoma. Successful ablation is defined by the combination of undetectable serum thyroglobulin levels after thyrotropin stimulation and normal results on neck ultrasonography 6 to 12 months after 131 I administration. 2 , 3 When these criteria are met, approximately 1% of patients have a recurrence. 4 – 6 In . . .

Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac regenerative potential correlates with cardiomyocyte cell-cycle arrest and polyploidization as well as the development of postnatal endothermy. We reveal that diploid cardiomyocyte abundance across 41 species conforms to Kleiber’s law—the ¾-power law scaling of metabolism with bodyweight—and inversely correlates with standard metabolic rate, body temperature, and serum thyroxine level. Inactivation of thyroid hormone signaling reduces mouse cardiomyocyte polyploidization, delays cell-cycle exit, and retains cardiac regenerative potential in adults. Conversely, exogenous thyroid hormones inhibit zebrafish heart regeneration. Thus, our findings suggest that loss of heart regenerative capacity in adult mammals is triggered by increasing thyroid hormones and may be a trade-off for the acquisition of endothermy.

In this trial, low-dose radioiodine was as effective as high-dose radioiodine in patients with differentiated thyroid tumors, and recombinant human thyrotropin (thyrotropin alfa) was as effective as thyroid hormone withdrawal. Thyroid cancer is the most frequently occurring endocrine cancer, with more than 2100 new cases each year in the United Kingdom and more than 48,000 in the United States. 1 , 2 Most cases are differentiated thyroid cancer, which is associated with a high 10-year survival rate (90 to 95%). 3 Many patients with differentiated thyroid cancer undergo radioiodine ablation to remove residual normal thyroid tissue after surgery. Some nonrandomized studies have suggested that radioiodine ablation reduces rates of death and recurrence. 4 – 7 However, there is uncertainty over the dose (administered activity) of radioiodine required for effective ablation. A systematic review of randomized . . .

Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. Limited studies suggest that exposure to DEHP may be associated with altered thyroid function, but detailed mechanisms are unclear. In order to elucidate potential mechanisms by which DEHP disturbs thyroid hormone homeostasis, Sprague-Dawley (SD) rats were dosed with DEHP by gavage at 0, 250, 500, and 750 mg/kg/day for 30 days and sacrificed within 24 h after the last dose. Gene expressions of thyroid hormone receptors, deiodinases, transthyretin, and hepatic enzymes were measured by RT-PCR; protein levels of transthyretin were also analyzed by Western blot. Results showed that DEHP caused histological changes in the thyroid and follicular epithelial cell hypertrophy and hyperplasia were observed. DEHP significantly reduced thyroid hormones (T3, T4) and thyrotropin releasing hormone (TRH) levels, whereas thyroid stimulating hormone (TSH) was not affected. After exposure to DEHP, biosynthesis of thyroid hormones was suppressed, and sodium iodide symporter (NIS) and thyroid peroxidase (TPO) levels were significantly reduced. Additionally, levels of deiodinases and transthyretin were also affected. TSH receptor (TSHr) level was downregulated, while TRH receptor (TRHr) level was upregulated. Metabolism of thyroid hormones was accelerated due to elevated gene expression of hepatic enzymes (UDPGTs and CYP2B1) by DEHP. Taken together, observed findings indicate that DEHP could reduce thyroid hormones through influencing biosynthesis, biotransformation, biotransport, receptor levels, and metabolism of thyroid hormones.

Our understanding of thyroid hormone action has been substantially altered by recent clinical observations of thyroid signaling defects in syndromes of hormone resistance and in a broad range of conditions, including profound mental retardation, obesity, metabolic disorders, and a number of cancers. The mechanism of thyroid hormone action has been informed by these clinical observations as well as by animal models and has influenced the way we view the role of local ligand availability; tissue and cell-specific thyroid hormone transporters, corepressors, and coactivators; thyroid hormone receptor (TR) isoform-specific action; and cross-talk in metabolic regulation and neural development. In some cases, our new understanding has already been translated into therapeutic strategies, especially for treating hyperlipidemia and obesity, and other drugs are in development to treat cardiac disease and cancer and to improve cognitive function.

Background Thyroid hormone (T3) has an inhibitory effect on tissue/organ regeneration. It is still elusive how T3 regulates this process. It is well established that the developmental effects of T3 are primarily mediated through transcriptional regulation by thyroid hormone receptors (TRs). Here we have taken advantage of mutant tadpoles lacking both TRα and TRβ (TRDKO), the only receptor genes in vertebrates, for RNA-seq analyses to investigate the transcriptome changes underlying the initiation of tail regeneration, i.e., wound healing and blastema formation, because this crucial initial step determines the extent of the functional regeneration in the later phase of tissue regrowth. Results We discovered that GO (gene ontology) terms related to inflammatory response, metabolic process, cell apoptosis, and epithelial cell migration were highly enriched among commonly regulated genes during wound healing at either stage 56 or 61 or with either wild type (WT) or TRDKO tadpoles, consistent with the morphological changes associated with wound healing occurring in both regenerative (WT stage 56, TRDKO stage 56, TRDKO stage 61) and nonregenerative (WT stage 61) animals. Interestingly, ECM-receptor interaction and cytokine-cytokine receptor interaction, which are essential for blastema formation and regeneration, were significantly enriched among regulated genes in the 3 regenerative groups but not the non-regenerative group at the blastema formation period. In addition, the regulated genes specific to the nonregenerative group were highly enriched with genes involved in cellular senescence. Finally, T3 treatment at stage 56, while not inducing any measurable tail resorption, inhibited tail regeneration in the wild type but not TRDKO tadpoles. Conclusions Our study suggests that TR-mediated, T3-induced gene regulation changed the permissive environment during the initial period of regeneration and affected the subsequent patterning/outgrowth period of the regeneration process. Specifically, T3 signaling via TRs inhibits the expression of ECM-related genes while promoting the expression of inflammation-related genes during the blastema formation period. Interestingly, our findings indicate that amputation-induced changes in DNA replication-related pathways can occur during this nonregenerative period. Further studies, particularly on the regenerative microenvironment that may depend on ECM-receptor interaction and cytokine-cytokine receptor interaction, should provide important insights on the regulation of regenerative capacity during vertebrate development.

Since the realization that the cellular homologs of a gene found in the retrovirus that contributes to erythroblastosis in birds (v-erbA), i.e. the proto-oncogene c-erbA encodes the nuclear receptors for thyroid hormones (THs), most of the interest for THs focalized on their ability to control gene transcription. It was found, indeed, that, by regulating gene expression in many tissues, these hormones could mediate critical events both in development and in adult organisms. Among their effects, much attention was given to their ability to increase energy expenditure, and they were early proposed as anti-obesity drugs. However, their clinical use has been strongly challenged by the concomitant onset of toxic effects, especially on the heart. Notably, it has been clearly demonstrated that, besides their direct action on transcription (genomic effects), THs also have non-genomic effects, mediated by cell membrane and/or mitochondrial binding sites, and sometimes triggered by their endogenous catabolites. Among these latter molecules, 3,5-diiodo-L-thyronine (3,5-T2) has been attracting increasing interest because some of its metabolic effects are similar to those induced by T3, but it seems to be safer. The main target of 3,5-T2 appears to be the mitochondria, and it has been hypothesized that, by acting mainly on mitochondrial function and oxidative stress, 3,5-T2 might prevent and revert tissue damages and hepatic steatosis induced by a hyper-lipid diet, while concomitantly reducing the circulating levels of low density lipoproteins (LDL) and triglycerides. Besides a summary concerning general metabolism of THs, as well as their genomic and non-genomic effects, herein we will discuss resistance to THs and the possible mechanisms of action of 3,5-T2, also in relation to its possible clinical use as a drug.

The deiodinase family of enzymes mediates the activation and inactivation of thyroid hormone. The role of these enzymes in the regulation of the systemic concentrations of thyroid hormone is well established and underpins the treatment of common thyroid diseases. Interest in this field has increased in the past 10 years as the deiodinases became implicated in tissue development and homeostasis, as well as in the pathogenesis of a wide range of human diseases. Three deiodinases have been identified, namely, types 1, 2 and 3 iodothyronine deiodinases, which differ in their catalytic properties and tissue distribution. Notably, the expression of these enzymes changes during the lifetime of an individual in relation to the different needs of each organ and to ageing. The systemic homeostatic role of deiodinases clearly emerges during changes in serum concentrations of thyroid hormone, as seen in patients with thyroid dysfunction. By contrast, the role of deiodinases at the tissue level allows thyroid hormone signalling to be finely tuned within a given cell in a precise time–space window without perturbing serum concentrations of thyroid hormone. This Review maps the overall functional role of the deiodinases and explores challenges and novel opportunities arising from the expanding knowledge of these ‘master’ components of the thyroid homeostatic system.This Review discusses the two main functions of the human deiodinases: the homeostatic control of plasma concentrations of thyroid hormone and the control of intracellular T3 concentrations.

Thyroid hormones (TH) play critical roles during nervous system development and patients carrying coding variants of MCT8 (monocarboxylate transporter 8) or THRA (thyroid hormone receptor alpha) present a spectrum of neurological phenotypes resulting from perturbed local TH action during early brain development. Recently, human cerebral organoids (hCOs) emerged as powerful in vitro tools for disease modelling recapitulating key aspects of early human cortex development. To begin exploring prospects of this model for thyroid research, we performed a detailed characterization of the spatiotemporal expression of MCT8 and THRA in developing hCOs. Immunostaining showed MCT8 membrane expression in neuronal progenitor cell types including early neuroepithelial cells, radial glia cells (RGCs), intermediate progenitors and outer RGCs. In addition, we detected robust MCT8 protein expression in deep layer and upper layer neurons. Spatiotemporal SLC16A2 mRNA expression, detected by fluorescent in situ hybridization (FISH), was highly concordant with MCT8 protein expression across cortical cell layers. FISH detected THRA mRNA expression already in neuroepithelium before the onset of neurogenesis. THRA mRNA expression remained low in the ventricular zone, increased in the subventricular zone whereas strong THRA expression was observed in excitatory neurons. In combination with a robust up-regulation of known T3 response genes following T3 treatment, these observations show that hCOs provide a promising and experimentally tractable model to probe local TH action during human cortical neurogenesis and eventually to model the consequences of impaired TH function for early cortex development.