Canine follicular cell and medullary thyroid carcinomas: Immunohistochemical characterization.

Research on modulation of iodine uptake by thyroid cells could help improve radioiodine treatment of dogs with thyroid tumors. The aim of this study was to characterize the immunohistochemical expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, thyroid peroxidase (TPO), vimentin, and Ki-67 in follicular cell thyroid carcinomas (FTCs) and medullary thyroid carcinomas (MTCs), and to compare protein expression between FTC causing hyperthyroidism and FTC of euthyroid dogs. Immunohistochemistry was performed in 25 FTCs (9 follicular, 8 follicular-compact, and 8 compact) and 8 MTCs. FTCs and MTCs were positive for TTF-1, and expression was higher in FTCs of euthyroid dogs compared with FTCs of hyperthyroid dogs (P= .041). Immunolabeling for thyroglobulin was higher in follicular and follicular-compact FTCs compared with compact FTCs (P = .001), while vimentin expression was higher in follicular-compact FTCs compared with follicular FTCs (P = .011). The expression of TSHR, NIS, pendrin, and TPO was not significantly different among the different subtypes of FTCs or between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. TSHR, NIS, pendrin, and TPO were also expressed in MTCs. Ki-67 labeling index was comparable between FTCs and MTCs, and between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. Proteins of iodine transport were also expressed in canine MTCs, which could have implications for diagnosis and treatment. The different expression of thyroglobulin and vimentin between FTC histological subtypes could reflect variations in tumor differentiation.

Placental leukocyte infiltration accompanies gestational changes induced by hyperthyroidism.

In brief: The endocrine and immunological disruption induced by hyperthyroidism could alter gestation, placenta, and fetal development. This study suggests an immunological role of thyroid hormones in gestation. Abstract: Thyroid dysfunctions lead to metabolic, angiogenic, and developmental alterations at the maternal-fetal interface that cause reproductive complications. Thyroid hormones (THs) act through their nuclear receptors that interact with other steroid hormone receptors. Currently, immunological regulation by thyroid status has been characterized to a far less extent. It is well known that THs exert regulatory function on immune cells and modulate cytokine expression, but how hyperthyroidism (hyper) modulates placental immunological aspects leading to placental alterations is unknown. This work aims to throw light on how hyper modulates immunological and morphological placental aspects. Control and hyper (induced by a daily s.c. injection of T4 0.25 mg/kg) Wistar rats were mated 8 days after starting T4 treatment and euthanized on days 19 (G19) and 20 (G20) of pregnancy. We removed the placenta to perform qPCR, flow cytometry, immunohistochemistry, Western blot and histological analysis, and amniotic fluid and serum to evaluate hormone levels. We observed that hyper increases the fetal number, fetal weight, and placental weight on G19. Moreover, hyper induced an endocrine imbalance with higher serum corticosterone and changed placental morphology, specifically the basal zone and decidua. These changes were accompanied by an increased mRNA expression of glucocorticoid receptor and monocyte chemoattractant protein-1, an increased mRNA and protein expression of prolactin receptor, and an increase in CD45+ infiltration. Finally, by in vitro assays, we evidenced that TH induced immune cell activation. In summary, we demonstrated that hyper modulates immunological and morphological placental aspects and induces fetal phenotypic changes, which could be related to preterm labor observed in hyper.

N-Acetylcysteine and Safranal prevented the brain damage induced by hyperthyroidism in adult male rats.

Background: Hyperthyroidism is associated with impairment in the neurotransmission and severe tissue damage in the brain. The present study explored the potential deleterious effects of experimentally-induced hyperthyroidism on the neurotransmitters, oxidative homeostasis, apoptosis and DNA fragmentation in cerebral cortex, thalamus & hypothalamus, and hippocampus in rats.Methods and Results: The ameliorative effects of N-acetylcysteine (NAC; 50 mg/kg, oral) and safranal (50 mg/kg, intraperitoneal) against hyperthyroidism (L-T4 500 µg/kg, subcutaneous) were investigated. All treatments continued daily over three weeks. Hyperthyroidism was manifested by significant elevations in serum fT3 and fT4 levels and a decline in serum TSH level and body weight. It was also characterized by significant elevations in the levels of dopamine, serotonin, and 5-hydroxyindole acetic acid, and monoamine oxidase activity to varying degrees in the brain regions examined and a significant reduction in norepinephrine in hippocampus only. Hyperthyroidism resulted in a significant oxidative stress in brain typified by elevations in malondialdehyde and nitric oxide content and reductions in glutathione level and SOD and catalase activities. This led to elevations in Caspases 9 and 3 and a reduction in Bcl2 resulting in DNA damage and confirmed by the histopathology of brain tissue. The administration of NAC or safranal with L-T4 prevented these deleterious effects by reducing the oxidative load and improving the brain antioxidant status.Conclusions: Hyperthyroidism disrupted the neurotransmitters in the brain which aggravated the oxidative stress and resulted in apoptosis. N-Acetylcysteine and safranal prevented these deleterious effects by enhancing the poor antioxidant milieu of the brain.

Neutropenia in patients with hyperthyroidism: Systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Neutropenia, a low absolute neutrophil count (ANC), may be a sign of new-onset hyperthyroidism. The aim of this systematic review and meta-analysis was to provide the most reliable estimates of prevalence, degree and response to treatments of neutropenia in the pure hyperthyroidism setting. METHODS: A comprehensive literature search was performed in PubMed and Scopus databases for retrieving articles in English and non-English languages reporting ANC values/neutropenic cases at presentation and after therapy in patients with hyperthyroidism. A proportion meta-analysis was performed with DerSimonian and Laird method (random-effects model). Pooled data were presented with 95% confidence intervals (95% CI) and displayed in a forest plot. I2 statistic index was used to quantify the heterogeneity among the studies. Sensitivity analyses for the prevalence of neutropenia and the mean of ANC in hyperthyroid patients were performed by excluding the studies without full details. Trim and fill analysis and Egger's linear regression test were carried out to evaluate the publication bias. A two-sided P-value of <.05 was regarded as significant for all analyses. The National Heart, Lung and Blood Institute Quality Assessment Tool was used to evaluate the quality of studies included. RESULTS: The literature search yielded 1880 studies of which 13 studies were included for systematic review and meta-analysis. Results of the meta-analysis demonstrated that the prevalence of neutropenia in newly diagnosed and untreated patients with Graves' hyperthyroidism was 10% (CI 5%-19%, I2 88.6%) and summary mean ANC value in neutropenic was 1.4 ± 0.3 × 109 /L. In all neutropenic patients under ATD therapy neutropenia resolved, thus without the worsening of the baseline ANC values or the development of agranulocytosis. The sensitivity analyses showed similar results as those of the main analyses. For all outcomes, the publication bias was not statistically significant or not calculable. CONCLUSIONS: Graves' disease per se is associated with neutropenia in about 10% of cases. Neutropenia usually appears as a mild to moderate laboratory abnormality with no detectable consequences. Subnormal/mild neutropenia should not be regarded as a contraindication to use ATDs, and clinicians should know that treating hyperthyroidism they have a significant chance to normalize ANC too.

The substance basis of Poria ameliorates hypothyroidism other than hyperthyroidism based on proteomics and metabolomics.

Integrated metabolomics and proteomics analysis was carried out to study the effects of Poria and its split components (volatile oil, triterpenoid, oligosaccharide, amino acid, and crude polysaccharide) on rats of normal physiological model, hyperthyroidism model, and hypothyroidism model to explore the substance basis of Poria for hypothyroidism from the perspective of a holistic view in substance and energy metalism. The key pathways regulating substance and energy metabolism were screened, encompassing tricarboxylic acid cycle pathway, glycolysis/ gluconeogenesis pathways, biosynthesis of amino acid pathway, fatty acid biosynthesis pathway, pentose phosphate pathway, peroxisome proliferator-activated receptors pathway, etc Poria and its split components showed promoting effects on substance and energy metabolism in normal model, while showed amelioration effects on hypothyroidism model at different degrees, and had no significant improvement effects on hyperthyroidism in rats. Volatile oil, triterpenoid, and crude polysaccharide from Poria were regarded as substance basis of Poria ameliorating hypothyroidism other than hyperthyroidism. This work also revealed the feasibility of metabolomics and proteomics analysis to elucidate the effective substance basis of traditional Chinese medicine from a new viewpoint based on its effects on substance and energy metabolism.

Functional State of Rat Heart Mitochondria in Experimental Hyperthyroidism.

In this work, the effect of thyroxine on energy and oxidative metabolism in the mitochondria of the rat heart was studied. Hyperthyroidism was observed in experimental animals after chronic administration of T4, which was accompanied by an increase in serum concentrations of free triiodothyronine (T3) and thyroxine (T4) by 1.8 and 3.4 times, respectively. The hyperthyroid rats (HR) had hypertrophy of the heart. In HR, there was a change in the oxygen consumption in the mitochondria of the heart, especially when using palmitoylcarnitine. The assay of respiratory chain enzymes revealed that the activities of complexes I, I + III, III, IV increased, whereas the activities of complexes II, II + III decreased in heart mitochondria of the experimental animals. It was shown that the level of respiratory complexes of the electron transport chain in hyperthyroid rats increased, except for complex V, the quantity of which was reduced. The development of oxidative stress in HR was observed: an increase in the hydrogen peroxide production rate, increase in lipid peroxidation and reduced glutathione. The activity of superoxide dismutase in the heart of HR was higher than in the control. At the same time, the activity of glutathione peroxidase decreased. The obtained data indicate that increased concentrations of thyroid hormones lead to changes in energy metabolism and the development of oxidative stress in the heart of rats, which in turn contributes to heart dysfunction.

A Blunted Sympathetic Function and an Enhanced Nitrergic Activity Contribute to Reduce Mesenteric Resistance in Hyperthyroidism.

We aimed to determine whether an experimental model of hyperthyroidism could alter the function of sympathetic and nitrergic components of mesenteric innervation. For this purpose, male Wistar rats were divided into (1) control rats (CT) and (2) rats infused with L-Thyroxine (HT). Body weight gain and adipose tissue accumulation were lower in HT rats, while systolic blood pressure and citrate synthase activity in the soleus muscle were increased by HT. In segments from the superior mesenteric artery, the application of an electrical field stimulation (EFS) induced a vasoconstrictor response, which was lower in arteries from HT animals. The alpha-adrenoceptor antagonist phentolamine diminished EFS-induced vasoconstriction to a lower extent in HT arteries, while the purinergic receptor antagonist suramin reduced contractile response to EFS only in segments from CT. In line with this, noradrenaline release, tyrosine hydroxylase expression and activation and dopamine ß hydroxylase expression were diminished in HT. The unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in segments from HT rats. NO release was enhanced in HT, probably due to an enhancement in neuronal NOS activity, in which a hyperactivation of both PKC and PI3K-AKT signaling pathways might play a relevant role. In conclusion, perivascular mesenteric innervation might contribute to reduce the vascular resistance observed in hyperthyroidism.

Evaluating Hyperthyroidism-Induced Liver Injury Based on In Situ Fluorescence Imaging of Glutathione and Phosphate via Nano-MOFs Sensor.

Hyperthyroidism-induced liver injury is quite common in clinical settings. Therefore, developing rapid and simple methods for the assessment of hyperthyroid liver injury is of great significance. Considering phosphorus metabolism is disordered because of hyperthyroidism, and the hyperthyroid liver injury is closely related to the abnormal level of glutathione (GSH). Thus, development of a new method that can simultaneously detect changes in blood phosphorus and GSH levels of serum, liver, kidney, and other organs to assess the degree of hyperthyroid liver injury is necessary for clinical medical research. Herein, a novel fluorescent metal-organic frameworks (MOFs) nanoprobe using the UiO-66(OH)2 as core and Cu-MOFs as shell was designed and synthesized. Through the specific action between Zr (IV) and phosphate, and the combine interaction of MOFs active center Cu (II) and GSH, high sensitivity and specific fluorescence detection of phosphate and GSH were achieved, respectively. Finally, the nanosensor was applied for evaluating different degrees of hyperthyroid liver injury in mice models and realized the monitoring of serum, liver, kidney, and other organs' blood phosphorus and GSH levels, and found that the levels of phosphate and GSH in serum were negatively correlated with the degree of hyperthyroid liver injury, while the changes of phosphate and GSH levels in the liver and kidney organs were positively correlated with the degree of hyperthyroid liver injury. In general, the present works provide a new way to effectively evaluate liver injury induced by hyperthyroidism in the early clinical stage.

Hyperthyroidism is associated with breast cancer risk and mammographic and genetic risk predictors.

BACKGROUND: Despite the biological link between thyroid hormones and breast cancer cell proliferation shown in experimental studies, little is known about the association between hyperthyroidism and breast cancer, as well as its association with the most common mammographic and genetic risk predictors for breast cancer. METHODS: This study estimates the incidence rate ratios (IRRs) of breast cancer among women diagnosed with hyperthyroidism, compared to those who are not, using two cohorts: a Swedish national cohort of the general female population (n = 3,793,492, 2002-2011) and the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, n = 69,598, 2002-2017). We used logistic regression to estimate the odds ratios (ORs) of hyperthyroidism according to the mammographic and genetic risk predictors for breast cancer. RESULTS: An increased risk of breast cancer was observed in patients in the national cohort with hyperthyroidism (IRR = 1.23, 95% CI = 1.12-1.36), particularly for toxic nodular goiter (IRR = 1.38, 95% CI = 1.16-1.63). Hyperthyroidism was associated with higher body mass index, early age at first birth, and lower breastfeeding duration. Higher mammographic density was observed in women with toxic nodular goiter, compared to women without hyperthyroidism. Additionally, among genotyped women without breast cancer in the KARMA cohort (N = 11,991), hyperthyroidism was associated with a high polygenic risk score (PRS) for breast cancer overall (OR = 1.98, 95% CI = 1.09-3.60) and for estrogen receptor-positive specific PRS (OR = 1.90, 95% CI = 1.04-3.43). CONCLUSION: Hyperthyroidism is associated with an increased risk of breast cancer, particularly for patients with toxic nodular goiter. The association could be explained by higher mammographic density among these women, as well as pleiotropic genetic variants determining shared hormonal/endocrine factors leading to the pathology of both diseases.

Local hyperthyroidism promotes pancreatic acinar cell proliferation during acute pancreatitis.

Proliferation of pancreatic acinar cells is a critical process in the pathophysiology of pancreatic diseases, because limited or defective proliferation is associated with organ dysfunction and patient morbidity. In this context, elucidating the signalling pathways that trigger and sustain acinar proliferation is pivotal to develop therapeutic interventions promoting the regenerative process of the organ. In this study we used genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones to elucidate their role in acinar proliferation following caerulein-mediated acute pancreatitis in mice. In addition, molecular mechanisms mediating the effects of thyroid hormones were identified by genetic and pharmacological inactivation of selected signalling pathways.In this study we demonstrated that levels of the thyroid hormone 3,3',5-triiodo-l-thyronine (T3) transiently increased in the pancreas during acute pancreatitis. Moreover, by using genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones, we showed that T3 was required to promote proliferation of pancreatic acinar cells, without affecting the extent of tissue damage or inflammatory infiltration.Finally, upon genetic and pharmacological inactivation of selected signalling pathways, we demonstrated that T3 exerted its mitogenic effect on acinar cells via a tightly controlled action on different molecular effectors, including histone deacetylase, AKT, and TGFß signalling.In conclusion, our data suggest that local availability of T3 in the pancreas is required to promote acinar cell proliferation and provide the rationale to exploit thyroid hormone signalling to enhance pancreatic regeneration. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[Hereditary predispositions to follicular thyroid tumors]. / Prédispositions héréditaires aux tumeurs thyroïdiennes de souche folliculaire.

Familial thyroid cancers of follicular origin are rare and include syndromic and non-syndromic tumours. In familial adenomatous polyposis, the prevalence of papillary thyroid cancer is 2-12% and in 20-40% of cases it is a cribriform-morular papillary thyroid carcinoma. Morules and cribriform pattern are the two main typical criteria, associated with a nuclear and cytoplasmic immunopositivity for beta catenin. DICER1 syndrome is associated with pleuropneumoblastoma, ovarian tumors and thyroid pathology (multinodular goiter and less frequently a well-differentiated thyroid cancer without microscopic particularity). Cowden syndrome is characterized by multiple hamartomas and two-thirds of patients develop thyroid pathology, including multinodular goiter (50-67%) and cancer (35%), the latter being one of the major diagnostic criteria of the syndrome. Classic triad of Carney complex associates lentiginosis, myxoid tumors, and various endocrine abnormalities; thyroid pathology occurs in 10% of cases and may be benign or malignant. In Werner's syndrome, thyroid cancer is present in 18% of cases. McCune-Albright syndrome is characterized by fibrous dysplasia, café-au-lait spots and various endocrinopathies including hyperthyroidism and nodular hyperplasia. Non-syndromic thyroid cancers, which represent the majority of familial cancers, are most often papillary carcinomas. In daily practice, in the presence of multiple benign thyroid nodules and/or thyroid cancer in a young person, or with family thyroid diseases, the pathologist should be aware about hereditary predispositions to propose an oncogenetic consultation.

Prenatal thyroxine treatment promotes anxiolysis in male Swiss mice offspring.

The proper functioning of the maternal thyroid plays a crucial role in fetal development. Thus, the aim of our study was to verify how maternal hyperthyroidism is able to change behavioral parameters in mice offspring during adulthood. For this purpose, pregnant Swiss mice (n = 24 and ~35 g) were randomly assigned into two groups: a control and a thyroxine (T4)-treatment group. The control was treated with 0.9% saline, while the treatment group received T4 (200 µg/kg, s.c.) once daily during the entire pregnancy period. After completing 70 days of life, a part of male offspring underwent a battery of tests, including open field, dark-light box, elevated plus maze, marble burying, rotarod and tail suspension tests. The other male pups were euthanized, being hippocampus and serum collected for RNA analysis and hormones measurement, respectively. Statistical analysis was performed using Student's t-test, and the means were considered significantly different when p < 0.05. In adult offspring, a significant decrease was observed for serum T3 in treated group. It was demonstrated that the T4 group had an increase in total distance traveled in an open field test. In the elevated plus maze test, we observed a higher time in opened arms as well as an increased in percentage of entries in these arms. In the hippocampus, T4 offspring had a higher expression of tryptophan hydroxylase 2 (TPH2), serotonin transporter (SERT) and glutamate decarboxylase 67 (GAD 67) in comparison to controls. These findings suggest that prenatal T4 treatment alters hippocampal serotonergic and GABAergic systems, promoting anxiolysis in male adult offspring.

Hippocampal Up-Regulation of Apolipoprotein D in a Rat Model of Maternal Hypo- and Hyperthyroidism: Implication of Oxidative Stress.

Thyroid disorders impair various functions of the hippocampus where thyroid hormone receptors are localized in the brain. Hyper and hypothyroidism are associated with large changes in brain oxidative stress. Apolipoprotein D (APOD) is a conserved glycoprotein that increased in response to oxidative stress in the brain and has been suggested function as an antioxidant in the brain. Thus, the goal of this work was to explore the effect of maternal hypo- and hyperthyroidism on the Apod expression in the pup's brain regarding changes in oxidative stress. For induction hypo and hyperthyroidism in adult female rats, 100 ppm propylthiouracil (PTU) and 8 ppm levothyroxine administrated 1 month before copulation to the week 3 after delivery in drinking water. The hippocampal region of rat pups was isolated and used for immunohistochemistry and quantitative RT-PCR on postnatal day (PND)5, PND10 and PND20. Results revealed that APOD over-expressed in both hypo- and hyperthyroid groups on PND5, PND10, and PND20. There was a proportional increase between the Apod expression and oxidative stress in the hyperthyroid group but not the hypothyroid in different days. Regarding the wide functions of thyroid hormones, oxidative stress does not suggest to be the only mechanism that involves Apod gene expression in thyroid disturbances.

A 2019 update on TSH-secreting pituitary adenomas.

Thyrotropin-secreting pituitary adenomas (TSH-omas) present with signs and symptoms of hyperthyroidism and they are characterized by elevated serum levels of free thyroid hormones with measurable TSH levels. TSH-omas are very infrequent, accounting for less than 1% of all pituitary adenomas, thus representing a very rare cause of hyperthyroidism. For this reason, data collected on these rare disorders are relatively few, but some new researches shed new light on the etiopathogenesis, the diagnosis and the treatment of such a remarkable disease. Since the same biochemical picture is present in the syndromes of thyroid hormone resistance (RTH), in particular in the form of pituitary RTH, failure in distinguishing these clinical entities may lead to improper patient management. Conversely, early diagnosis and correct treatment of TSH-omas may prevent the occurrence of neurological and endocrinological complications, thus leading to a better rate of cure. In the present short review article, the most relevant recent advances in the pathophysiology of TSH-omas are described.

An improved mouse model of Graves disease by once immunization with Ad-TSHR289.

The novel Graves disease (GD) model was established in BALB/c mice with recombinant adenovirus expressing the full-length human TSHR (Ad-TSHR289) by three times immunizations for nearly three months. Reducing the frequency of immunizations may shorten the modeling time to improve the efficiency of the study. In this study, female BALB/c mice were immunized one time with an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). At the 3, 6, 12, 17 weeks after the immunization, mice were sacrificed. The blood was collected and thyroids were removed. T3, T4, TRAB and thyroid weight/body weight (TW/BW) were tested. Compared with the Normal control (NC) group, the incidence of hyperthyroidism at 3, 6, 12 and 17 weeks after immunization were about 66.67%, 100%, 100%, and 100%. Meanwhile, the incidences of goiter were nearly 50%, 83.33%, 100% and 100% at the same stages. Therefore, modeling rates of GD were about 50%, 83.33%, 100%, 100% at 3, 6, 12 and 17 weeks after immunization. T3 in serum continues to increase from 3 weeks to 17 weeks after immunization. Serum TRAb reached to peak at 6 weeks and remained from 12 weeks after immunization, while T4 and TW/BW had kept steady from 6 weeks. There are positive correlations between T3, T4 and TRAb, TRAb and TW/BW, as well as T3, T4 and TW/BW. GD model can be constructed by primary immunization with Ad-TSHR289, which could be detected at 3 weeks and at least until the 17 weeks after primary immunization. It would improve the efficiency of GD research.

Energy Metabolism in the Bone is Associated with Histomorphometric Changes in Rats with Hyperthyroidism.

BACKGROUND/AIMS: In this study we assessed histomorphometric changes induced by thyroxine (T4) in 3-month-old hyperthyroid male rats and examined whether the potential mechanism of these changes is related to bone changes. METHODS: Rats were classified as either hyperthyroid following administration of 250 µg/kg/day freshly prepared T4 by gavage for 2 months or euthyroid following administration of vehicle alone (n = 8 per group). We measured bone mineral density (BMD), bone biomechanical properties, and bone histomorphometric changes. Levels of serum indicators were also measured, and three right femurs from the two groups were selected for proteomic investigation. RESULTS: Compared with the control rats, hyperthyroid rats showed a reduction in the fifth lumbar vertebral BMD as well as in the entire femoral BMD (p = 0.033 and 0.026, respectively). Histomorphometric analysis of the proximal tibial metaphysis showed that the percentage of the trabecular area, trabecular number, and percentage of the cortical bone area in the hyperthyroid rats significantly decreased compared with those of the control rats. Conversely, bone formation rate (per unit of bone surface and bone volume), percentage of the osteoclast perimeter, trabecular separation, and endosteal mineral apposition rate in the hyperthyroid rats significantly increased compared with the control rats (all p < 0.05). Except for stiffness (p = 0.24), all bone biomechanical properties of the femur showed a significant decreasing trend in the hyperthyroid rats versus the control rats (all p < 0.05). Serum levels of osteocalcin, alkaline phosphatase, terminal telopeptides of type ß collagen, and tartrate-resistant acid phosphatase were higher in the hyperthyroid rats than in the control rats (all p < 0.05). Using isobaric tags for relative and absolute quantification (iTRAQ), the expression levels of 1,310 proteins were found to be significantly different between the hyperthyroid and control rats (711 proteins were upregulated and 599 were downregulated in hyperthyroid rats). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that most of the enzymes in the glycolysis-tricarboxylic acid (TCA) cycle-oxidative phosphorylation signalling pathway were upregulated in hyperthyroid rats, and seven differentially expressed proteins were selected to verify the iTRAQ results using western blotting. CONCLUSION: Energy metabolism via the glycolysis-TCA cycle-oxidative phosphorylation pathway is positively associated with T4-induced bone histomorphometric changes in rats.

Detection of Parathyroid Autofluorescence Using Near-Infrared Imaging: A Multicenter Analysis of Concordance Between Different Surgeons.

BACKGROUND: Parathyroid glands (PGs) exhibit autofluorescence (AF) when excited by near-infrared laser. This multicenter study aims to analyze how this imaging could facilitate the detection of PGs during thyroidectomy and parathyroidectomy procedures. METHODS: This was a retrospective Institutional Review Board-approved analysis of prospectively collected data at three centers. Near-infrared fluorescence imaging (NIFI) was used to detect AF from PGs during thyroidectomy and parathyroidectomy procedures. Logistic regression analysis was performed to assess the utility of NIFI to identify PGs and concordance at these centers. RESULTS: Overall, 210 patients underwent total thyroidectomy (n = 95), thyroid lobectomy (n = 41), and parathyroidectomy (n = 74) (n = 70 per center). Using NIFI, AF was detected from 98% of visually identified PGs. Upon initial exploration, 46% of PGs were not visible to the naked eye due to coverage by soft tissue, but AF from these glands could be detected by NIFI without any further dissection. Overall, a median of one PG per patient was detected by NIFI in this fashion before being identified visually (p = nonsignificant between centers). On logistic regression, smaller PGs were more likely to be missed visually, but localized by AF on NIFI (odds ratio with increasing size, 0.91; p = 0.02). CONCLUSIONS: In our experience, NIFI facilitated PG identification by detecting their AF, before conventional recognition by the surgeon, in 37-67% of the time. Despite the variability in this rate across centers, there was a concordance in detecting AF from 97 to 99% of the PGs using NIFI. We suggest the incorporation of AF on NIFI alongside conventional visual cues to aid identification of PGs during neck operations.

Association between circulating irisin levels and epicardial fat in patients with treatment-naïve overt hyperthyroidism.

BACKGROUND: Hyperthyroidism is associated with increased metabolic activity and thermogenesis. Irisin is a key molecule in thermogenesis and energy expenditure via adipose tissue browning. Epicardial fat was previously defined as brown-like fat. Thus, here we aimed to evaluate the association between serum irisin level and epicardial fat thickness (EFT) in patients with hyperthyroidism. METHODS: A total of 25 hyperthyroid patients and 24 age-, sex- and BMI-matched healthy controls were enrolled. Serum irisin levels, thyroid hormone levels, and body compositions were compared. EFT was measured via transthoracic echocardiography. RESULTS: Serum irisin level and EFT were significantly higher in the hyperthyroid group (p < 0.001 and p = 0.001, respectively). The distributions of fat-free mass, muscle mass and fat mass were similar between the study groups. Serum irisin level was negatively correlated with TSH (p < 0.001) and positively correlated with fT3 (p < 0.001), fT4 (p < 0.001) and TSH receptor antibody (p = 0.002) levels and EFT (p = 0.001). In multivariate linear regression analysis, TSH (ß = -0.475, p < 0.001) and EFT (ß = 0.290, p = 0.023) levels were significantly associated with serum irisin levels. CONCLUSIONS: An increased serum irisin level associated with EFT might contribute to metabolic derangement in hyperthyroidism. Further studies are needed to elucidate whether irisin levels and EFT are affected by hyperthyroidism or vice versa.

Opposing Effects of Maternal Hypo- and Hyperthyroidism on the Stability of Thalamocortical Synapses in the Visual Cortex of Adult Offspring.

Insufficient or excessive thyroid hormone (TH) levels during fetal development can cause long-term neurological and cognitive problems. Studies in animal models of perinatal hypo- and hyperthyroidism suggest that these problems may be a consequence of the formation of maladaptive circuitry in the cerebral cortex, which can persist into adulthood. Here we used mouse models of maternal hypo- and hyperthyroidism to investigate the long-term effects of altering thyroxine (T4) levels during pregnancy (corresponding to embryonic days 6.5-18.5) on thalamocortical (TC) axon dynamics in adult offspring. Because perinatal hypothyroidism has been linked to visual processing deficits in humans, we performed chronic two-photon imaging of TC axons and boutons in primary visual cortex (V1). We found that a decrease or increase in maternal serum T4 levels was associated with atypical steady-state dynamics of TC axons and boutons in V1 of adult offspring. Hypothyroid offspring exhibited axonal branch and bouton dynamics indicative of an abnormal increase in TC connectivity, whereas changes in hyperthyroid offspring were indicative of an abnormal decrease in TC connectivity. Collectively, our data suggest that alterations to prenatal T4 levels can cause long-term synaptic instability in TC circuits, which could impair early stages of visual processing.

Neonatal exposure to T3 disrupts male reproductive functions by altering redox homeostasis in immature testis of rats.

T3 is the active hormone, produced by peripheral deiodination of thyroxine. Exposure to excess thyroid hormones leads to hypermetabolic state and thus generates oxidative stress which seems to be involved in hyperthyroidism-induced testicular pathophysiology. We investigated the effects of T3 administration on the testis during development throughout sexual maturation in rats. Male pups were divided into two groups. T3 group was administered 80 µg/kg body weight intraperitoneal T3 injections daily for 21 days from the 1st postnatal day, while the control group was administered saline intraperitoneal injections. The pups were sacrificed at pnd 10, 20 and 30. T3 treatment resulted in a significant decrease in body weight at all ages tested and an increase in testis weight during the treatment period. The treatment produced imbalance in their testicular redox status, reflected by a significant increase in the amount of thiobarbituric acid-reactive substances and protein carbonyl content in the testicular homogenates of 20-day-old rats. We observed a significant increase in antioxidant system activities γ-glutamyl transferase, glucose-6-phosphate dehydrogenase, catalase and superoxide dismutase, reduced glutathione content and lactate dehydrogenase activity. Histological examination showed altered seminiferous tubules, degenerated germ cells and decreased height of the germinal epithelium. Chronic neonatal exposure to T3 resulted in redox state alterations which contribute to testicular impairment.