Comparative cardiac macroscopic and microscopic study in cats with hyperthyroidism vs. cats with hypertrophic cardiomyopathy.

Hyperthyroidism is considered the most common endocrinopathy in middle-aged and old cats. The increased level of thyroid hormones influences many organs, including the heart. Cardiac functional and structural abnormalities in cats with hyperthyroidism have indeed been previously described. Nonetheless, myocardial vasculature has not been subjected to analysis. Also, no comparison with hypertrophic cardiomyopathy has been previously described. Although it has been shown that clinical alterations resolve after the treatment of hyperthyroidism, no detailed data have been published on the cardiac pathological or histopathological image of field cases of hyperthyroid cats that received pharmacological treatment. The aim of this study was to evaluate the cardiac pathological changes in feline hyperthyroidism and to compare them to alterations present in cardiac hypertrophy due to hypertrophic cardiomyopathy in cats. The study was conducted on 40 feline hearts divided into three groups: 17 hearts from cats suffering from hyperthyroidism, 13 hearts from cats suffering from idiopathic hypertrophic cardiomyopathy and 10 hearts from cats without cardiac or thyroid disease. A detailed pathological and histopathological examination was performed. Cats with hyperthyroidism showed no ventricular wall hypertrophy in contrast to cats with hypertrophic cardiomyopathy. Nonetheless, histological alterations were similarly advanced in both diseases. Moreover, in hyperthyroid cats more prominent vascular alterations were noted. In contrast to hypertrophic cardiomyopathy, the histological changes in hyperthyroid cats involved all ventricular walls and not mainly the left ventricle. Our study showed that despite normal cardiac wall thickness, cats with hyperthyroidism show severe structural changes in the myocardium.

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.

Incidence and Risk Factors of Thyroid Malignancy in Patients with Toxic Nodular Goiter.

Background: Although hyperfunctioning thyroid disorders were thought to be protective against malignancy, some recent studies reported a high incidence of incidentally discovered cancer in patients with hyperfunctioning benign thyroid disorders. We performed this study to estimate the incidence and predictors of malignant thyroid disease in patients with toxic nodular goiter (TNG). Patients and Methods. The data of 98 patients diagnosed with TNG were reviewed (including toxic multinodular goiter SMNG and single toxic nodule STN). The collected data included patients age, gender, systemic comorbidities, family history of thyroid malignancy, previous neck radiation, type of disease (multinodular or single), size of the dominant nodule by the US, operative time, and detection of significant lymph nodes during operation. Based on the histopathological analysis, the cases were allocated into benign and malignant groups. Results: Malignancy was detected in 21 patients (21.43%). Although age distribution was comparable between the two groups, males showed a significant increase in association with malignancy. Medical comorbidities and family history of cancer did not differ between the two groups. However, TMNG showed a statistically higher prevalence in the malignant group. Operative data, including operative time and lymph node detection, were comparable between the two groups. On regression analysis, both male gender and TMNG were significant predictors of malignancy. Conclusion: The presence of thyroid hyperfunction is not a protective factor against malignancy, as malignancy was detected in about 1/5 of cases. Male gender and TMNG were significant risk factors of malignancy in such patients.

Bone mineral density (BMD) and neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) in childhood thyroid diseases.

OBJECTIVE: This study aimed at investigating the laboratory parameters related to the pathogenesis of bone loss, including bone mineral density (BMD), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) in children with thyroid disease and healthy controls. PATIENTS AND METHODS: Children and adolescents with hypothyroidism (n=63) and hyperthyroidism (n=30) as well as 32 age- and sex-matched healthy controls were included in the study. Auxological data, BMD, hemogram parameters, the levels of thyroid hormone, thyroid stimulating hormone (TSH), thyroid autoantibodies, parathyroid hormone, 25-hydroxy vitamin D, alkaline phosphatase, calcium, and phosphorus were analyzed. RESULTS: The mean age of the patients was 12.12±2.7 years (range: 8-17). BMD Z-scores were within the normal range in all the patients and healthy controls. The BMD Z-scores were significantly higher in patients with hyperthyroidism than those in the control group and in patients with hypothyroidism. No significant difference was observed between the control and hypothyroid groups in terms of the BMD Z-scores. A correlation was observed between the BMD Z-scores and NLR, MLR, PLR, and free T4 levels. In patients with hypothyroidism, the BMD Z-scores were significantly positively correlated with the NLR, MLR, PLR, and the TSH level. In the control group, there was a moderate positive correlation between the BMD Z-scores and NLR. In the hyperthyroid group, there were no significant correlations between the BMD Z-scores and other variables. CONCLUSIONS: The study data suggest that in children and adolescents with thyroid disease, the relationship between the BMD Z-scores and NLR, MLR, and PLR at the initial diagnosis in the hypothyroidism group was different from that in their healthy peers.

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.

A Longitudinal Study of Medial Temporal Lobe Volumes in Graves Disease.

CONTEXT: Neuropsychiatric symptoms are common features of Graves disease (GD) in hyperthyroidism and after treatment. The mechanism behind these symptoms is unknown, but reduced hippocampal volumes have been observed in association with increased thyroid hormone levels. OBJECTIVE: This work aimed at investigating GD influence on regional medial temporal lobe (MTL) volumes. METHODS: Sixty-two women with newly diagnosed GD underwent assessment including magnetic resonance (MR) imaging in hyperthyroidism and 48 of them were followed up after a mean of 16.4 ±â€…4.2 SD months of treatment. Matched thyroid-healthy controls were also assessed twice at a 15-month interval. MR images were automatically segmented using multiatlas propagation with enhanced registration. Regional medial temporal lobe (MTL) volumes for amygdalae and hippocampi were compared with clinical data and data from symptom questionnaires and neuropsychological tests. RESULTS: Patients had smaller MTL regions than controls at inclusion. At follow-up, all 4 MTL regions had increased volumes and only the volume of the left amygdala remained reduced compared to controls. There were significant correlations between the level of thyrotropin receptor antibodies (TRAb) and MTL volumes at inclusion and also between the longitudinal difference in the levels of free 3,5,3'-triiodothyronine and TRAb and the difference in MTL volumes. There were no significant correlations between symptoms or test scores and any of the 4 MTL volumes. CONCLUSION: Dynamic alterations in the amygdalae and hippocampi in GD reflect a previously unknown level of brain involvement both in the hyperthyroid state of the condition and after treatment. The clinical significance, as well as the mechanisms behind these novel findings, warrant further study of the neurological consequences of GD.

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.

Smoothelin-Like Protein 1 Regulates Development and Metabolic Transformation of Skeletal Muscle in Hyperthyroidism.

Hyperthyroidism triggers a glycolytic shift in skeletal muscle (SKM) by altering the expression of metabolic proteins, which is often accompanied by peripheral insulin resistance. Our previous results show that smoothelin-like protein 1 (SMTNL1), a transcriptional co-regulator, promotes insulin sensitivity in SKM. Our aim was to elucidate the role of SMTNL1 in SKM under physiological and pathological 3,3',5-Triiodo-L-thyronine (T3) concentrations. Human hyper- and euthyroid SKM biopsies were used for microarray analysis and proteome profiler arrays. Expression of genes related to energy production, nucleic acid- and lipid metabolism was changed significantly in hyperthyroid samples. The phosphorylation levels and activity of AMPKα2 and JNK were increased by 15% and 23%, respectively, in the hyperthyroid samples compared to control. Moreover, SMTNL1 expression showed a 6-fold decrease in the hyperthyroid samples and in T3-treated C2C12 cells. Physiological and supraphysiological concentrations of T3 were applied on differentiated C2C12 cells upon SMTNL1 overexpression to assess the activity and expression level of the elements of thyroid hormone signaling, insulin signaling and glucose metabolism. Our results demonstrate that SMTNL1 selectively regulated TRα expression. Overexpression of SMTNL1 induced insulin sensitivity through the inhibition of JNK activity by 40% and hampered the non-genomic effects of T3 by decreasing the activity of ERK1/2 through PKCδ. SMTNL1 overexpression reduced IRS1 Ser307 and Ser612 phosphorylation by 52% and 53%, respectively, in hyperthyroid model to restore the normal responsiveness of glucose transport to insulin. SMTNL1 regulated glucose phosphorylation and balances glycolysis and glycogen synthesis via the downregulation of hexokinase II by 1.3-fold. Additionally, mitochondrial respiration and glycolysis were measured by SeaHorse analysis to determine cellular metabolic function/phenotype of our model system in real-time. T3 overload strongly increased the rate of acidification and a shift to glycolysis, while SMTNL1 overexpression antagonizes the T3 effects. These lines of evidence suggest that SMTNL1 potentially prevents hyperthyroidism-induced changes in SKM, and it holds great promise as a novel therapeutic target in insulin resistance.

Relapse of Human Chorionic Gonadotropin-Induced Hyperthyroidism and Severe Hyperemesis Gravidarum Secondary to Twin-Twin Transfusion Syndrome, With Rapid Recovery Following Fetoscopic Laser Coagulation: Case Report.

Background: Limited data have shown that, compared to uncomplicated twin pregnancies, pregnancies complicated by twin-twin transfusion syndrome (TTTS), a life-threatening condition, are associated with higher maternal serum levels of both human chorionic gonadotropin (hCG) and thyroid hormones. With the continuing expansion of assisted reproductive technologies, the rate of twin pregnancies, including those complicated by TTTS and associated hyperemesis gravidarum, is expected to increase further. Therefore, detailed descriptions of the maternal and fetal clinical outcomes of maternal thyrotoxicosis linked to TTTS can be useful for timely diagnosis and management. However, such descriptions are currently lacking in the literature. Case Presentation: We report the case of a 30-year-old woman carrying a monochorionic twin pregnancy complicated by TTTS that induced a relapse of severe hyperemesis gravidarum with overt non-autoimmune hyperthyroidism at 17 weeks of gestation. Following fetoscopic laser coagulation (FLC), both hyperemesis and hyperthyroidism improved within 1 week. Conclusions: The present experience contributes to the knowledge base on maternal thyrotoxicosis linked to TTTS and can be useful in the diagnosis and treatment of future cases; it also emphasizes the need for a high degree of clinical suspicion and for close collaboration between endocrinologists and obstetricians. Another key point is that TTTS-associated hyperemesis gravidarum and maternal hyperthyroidism should be considered in the differential diagnosis of refractory or relapsing hyperemesis gravidarum in women with monochorionic twin pregnancy, because this condition may require more stringent supportive treatment before and during the FLC procedure when the mother is overtly hyperthyroid.

Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Because subclinical hyperthyroidism increases the risk of osteoporosis and fractures, concerns are growing about the long-term skeletal safety of TSH suppression therapy after total thyroidectomy in patients with differentiated thyroid cancer (DTC). OBJECTIVE: We aimed to determine the effect of TSH suppression therapy on bone mineral density (BMD) in DTC patients. METHODS: We searched PubMed, Embase, the Cochrane library, and other sources. Eligible observational studies included DTC patients who underwent TSH suppression therapy and BMD measurement. Two independent reviewers extracted data on the studies' characteristics and outcomes and determined their risk of bias. Data were extracted from each study for postmenopausal/premenopausal women's and men's lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD and summed using a random-effects meta-analysis model. The weighted mean differences with 95% CIs are expressed for the differences in outcome measurements between groups. RESULTS: Seventeen studies (739 patients and 1085 controls) were included for quantitative analysis. In postmenopausal women, TSH suppression therapy showed a significant decrease in LS BMD (-0.03; -0.05, -0.02), and a similar trend was seen in TH. In premenopausal women, TSH suppression therapy significantly increased LS BMD (0.04; 0.02, 0.06) and FN BMD (0.02; 0.01, 0.04). In men, there was no significant association between TSH suppression therapy and BMD at any site compared with the controls. CONCLUSION: Evidence from observational studies suggests that postmenopausal women treated with TSH suppression therapy are at risk for lower BMD. Attention should be paid to long-term skeletal safety in DTC survivors.

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.

"Is there any reason to treat subclinical hypo and hyperthyroidism?"

Subclinical thyroid disease represents an early stage of thyroid dysfunction, which is usually asymptomatic and biochemically defined; its diagnosis can be performed thanks to the high sensitivity of the hypothalamic-pituitary-thyroid axis. The approach to this disorder requires correct diagnosis, clinical assessment and treatment. Cardiovascular diseases (e.g. atrial fibrillation, heart failure, and coronary heart disease), bone loss and fractures, and dementia represent the main adverse events of severe subclinical hyperthyroidism with undetectable TSH levels. Treatment of patients with subclinical hypothyroidism with a serum TSH level above 10 mIU/L is justified in order to reduce the risks of coronary heart disease and heart failure.

Familial neonatal nonautoimmune hyperthyroidism due to a gain-of-function (D619G) thyrotropin-receptor mutation.

OBJECTIVES: Activating germline mutations of the thyroid-stimulating hormone receptor (TSHR) are responsible for a rare form of neonatal nonautoimmune hyperthyroidism (NAH). We report the first case of familial neonatal neonatal nonautoimmune associated with c.1856A>G (p.Asp619Gly) variant in the TSHR gene. CASE PRESENTATION: We describe an eight-year-old African-American female presenting with neonatal NAH associated with an inherited heterozygous c.1856A>G (p.Asp619Gly) variant in the TSHR gene. This variant was previously described in one patient presenting with sporadic NAH in adolescence. Our patient was diagnosed with hyperthyroidism in the neonatal period. The mother had a history of hyperthyroidism and had thyroidectomy at the age of 4 years. The patient had goiter and elevated free thyroxine (FT4) and free triiodothyronine (FT3) levels that normalized with methimazole treatment; however, TSH level remained suppressed. Thyroid antibodies were negative. The patient also had bilateral exotropia, a trait shared by the mother and may represent a new association. CONCLUSIONS: Familial neonatal NAH is associated with heterozygous c.1856A>G (p.Asp619Gly) variant of the TSHR gene.

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.

Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM).

OBJECTIVES: Treatment of children with Hashimoto thyroiditis (HT) and particularly of those with coexistent diabetes mellitus type 1 (TIDM) and normal/mildly elevated serum TSH is controversial. The aim of the study was to evaluate the natural course of HT in children with TIDM compared with children with no other coexistent autoimmunity and investigate for possible predictive factors of thyroid function deterioration. METHODS: Data from 96 children with HT, 32 with T1DM (23 girls, nine boys) mean (sd) age: 10.6 (2.3) years, and 64 age and sex-matched without T1DΜ (46 girls, 18 boys), mean (sd) age: 10.2 (2.9) years were evaluated retrospectively. They all had fT4 and TSH values within normal ranges and available data for at least three years' follow-up. RESULTS: During the follow-up period, 11 children (34.4%) with TIDM exhibited subclinical hypothyroidism and two children (6.2%) progressed to overt hypothyroidism compared to 12 (18.8%) and two (3.1%) among children without TIDM, respectively. Among children with HT, a higher percentage (40.6%) of children with T1DM progressed to subclinical or overt hypothyroidism, compared with children (21.9%) with similar characteristics but without TIDM or other coexistent autoimmunity. CONCLUSIONS: The annual conversion rate from euthyroidism to hypothyroidism in children with T1DM was significantly higher compared to sex and age-matched children without TIDM. Prospective randomized trials are needed to support the view of an earlier intervention therapy even in milder degrees of thyroid failure in these children.

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.

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.

Effect of lithium carbonate on the function of the thyroid gland: mechanism of action and clinical implications.

Lithium carbonate, a drug known for more than 100 years, has been successfully used as a psychiatric medication. Currently, it is a commonly used drug to treat patients with unipolar and bipolar depression, and for the prophylaxis of bipolar disorders and acute mania. Lithium salts may cause the development of goiter, hypothyroidism, or rarely hyperthyroidism. The present review examined the current state of knowledge on the effect of lithium carbonate on the thyroid gland. The Pubmed database and Google Scholar were searched for articles related to the effects of lithium therapy on the thyroid gland function published up to February 2020. Studies that examined the mechanism of action of lithium at the molecular level, including pharmacokinetics, and focused on its effects on the thyroid gland were included. Lithium as a mood-stabilizing drug has a complex mechanism of action. Because of the active transport of Na+/I- ions, lithium, despite its concentration gradient, is accumulated in the thyroid gland at a concentration 3 - 4 times higher than that in the plasma. It can inhibit the formation of colloid in thyrocytes, change the structure of thyroglobulin, weaken the iodination of tyrosines, and disrupt their coupling. In addition, it reduces the clearance of free thyroxine in the serum, thereby indirectly reducing the activity of 5-deiodinase type 1 and 2 and reducing the deiodination of these hormones in the liver. Taken together, this review provides recommendations for monitoring the thyroid gland in patients who require long-term lithium therapy. Prior to the initiation of lithium therapy, thyroid ultrasound should be performed, and the levels of thyroid hormones (fT3 and fT4), TSH, and antithyroid peroxidase and antithyroglobulin antibodies should be measured. If the patient shows normal thyroid function, TSH level measurement and thyroid ultrasound should be performed at 6- to 12-month intervals for long term.

Effect of ß-casomorphin-7 on myocardial hypertrophy in hyperthyroidism-induced cardiomyopathy.

OBJECTIVE: The purpose of this study was to investigate the effect of ß-casomorphin-7 (ß-CM-7) on myocardial hypertrophy (MH) in hyperthyroidism-induced cardiomyopathy in vivo and in vitro. MATERIALS AND METHODS: Thirty C56BL/6 mice were randomly divided into three groups: control group, hyperthyroidism group, and ß-CM-7 treatment group. An animal model of cardiac hypertrophy of hyperthyroid heart disease (HHD) was constructed by continuous intraperitoneal injection of 100 µg of L-thyroxine (L-Thy) for 28 days, and the serum TT3 and TT4 concentrations were measured. After that, myocardial specimens were collected to measure left and right ventricular MH index, and the myocardial cell structure was observed under hematoxylin and eosin (HE) staining. Thereafter, Masson staining was adopted to determine collagen volume fraction, and hydroxylamine method was used to measure superoxide dismutase (SOD) activity, Meanwhile, DTNB direct method was applied to measure GSH-Px activity, thio-malonylurea method was utilized to measure malondialdehyde (MDA) content, and the level of reactive oxygen species (ROS) was detected by flow cytometry. Finally, the expressions of oxidative stress (OS) and inflammation-related factors in vivo and the nuclear factor-κB (NF-κB) pathway in vitro were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared with those in control group, TT3 and TT4 were remarkably increased, the structure of myocardial cells was disordered, the interstitial fibrosis and the ventricular MH index were significantly increased, the OS and inflammatory responses were increased, and the NF-κB pathway was activated in the Hyperthyroidism group. In the ß-CM-7 group, the content of TT3 and TT4 was decreased, the myocardial cell structure was slightly disturbed, the fibrosis and the ventricular MH index were reduced, OS and inflammatory response were reduced, and the NF-κB pathway was inhibited. CONCLUSIONS: ß-CM-7 can prevent and treat MH in mice with L-Thy-induced HHD probably through regulating the NF-κB signaling pathway.