leptin and Thyroid-Neoplasms

The clinical behavior of thyroid cancers is seen to reflect inherent transcriptional activities of mutated genes and trophic effects on tumors of circulating pituitary thyrotropin (TSH). The thyroid hormone, L-thyroxine (T4), has been shown to stimulate proliferation of a large number of different forms of cancer. This activity of T4 is mediated by a cell surface receptor on the extracellular domain of integrin αvβ3. In this brief review, we describe what is known about T4 as a circulating trophic factor for differentiated (papillary and follicular) thyroid cancers. Given T4's cancer-stimulating activity in differentiated thyroid cancers, it was not surprising to find that genomic actions of T4 were anti-apoptotic. Transduction of the T4-generated signal at the integrin primarily involved mitogen-activated protein kinase (MAPK). In thyroid C cell-origin medullary carcinoma of the thyroid (MTC), effects of thyroid hormone analogues, such as tetraiodothyroacetic acid (tetrac), include pro-angiogenic and apoptosis-linked genes. Tetrac is an inhibitor of the actions of T4 at αvβ3, and it is assumed, but not yet proved, that the anti-angiogenic and pro-apoptotic actions of tetrac in MTC cells are matched by T4 effects that are pro-angiogenic and anti-apoptotic. We also note that papillary thyroid carcinoma cells may express the leptin receptor, and circulating leptin from adipocytes may stimulate tumor cell proliferation. Transcription was stimulated by leptin in anaplastic, papillary, and follicular carcinomas of genes involved in invasion, such as matrix metalloproteinases (MMPs). In summary, thyroid hormone analogues may act at their receptor on integrin αvβ3 in a variety of types of thyroid cancer to modulate transcription of genes relevant to tumor invasiveness, apoptosis, and angiogenesis. These effects are independent of TSH.

Topics: Animals; Gene Expression Regulation, Neoplastic; Humans; Integrin alphaVbeta3; Leptin; Thyroid Neoplasms; Thyroxine

The incidence of thyroid carcinoma is increasing all over the world. Some studies have suggested that the change of adipokines expression can induce thyroid carcinoma. However, other studies have come to the opposite conclusion. Therefore, we studied the relationship between adipokines and thyroid carcinoma.. Databases-PubMed, Cochrane Library, SinoMed, CNKI, Wanfang, and clinical trial registries were searched. A meta-analysis was then performed through a fixed or random-effects model to calculate I values for heterogeneity analysis.. Adipokines (TNF-α, IL-6 and leptin) show a strong relationship between elevated concentrations (in serum and/or tissue) and thyroid carcinoma. However, the association between adiponectin and thyroid carcinoma needs further research.

Topics: Adipocytes; Adiponectin; Carcinoma; Case-Control Studies; Humans; Incidence; Interleukin-6; Leptin; Risk Factors; Thyroid Gland; Thyroid Neoplasms; Tumor Necrosis Factor-alpha

Obesity and thyroid diseases are common disorders in the general population and they frequently occur in single individuals. Alongside a chance association, a direct relationship between 'thyroid and obesity' has been hypothesized. Thyroid hormone is an important determinant of energy expenditure and contributes to appetite regulation, while hormones and cytokines from the adipose tissue act on the CNS to inform on the quantity of energy stores. A continuous interaction between the thyroid hormone and regulatory mechanisms localized in adipose tissue and brain is important for human body weight control and maintenance of optimal energy balance. Whether obesity has a pathogenic role in thyroid disease remains largely a matter of investigation. This review highlights the complexity in the identification of thyroid hormone deficiency in obese patients. Regardless of the importance of treating subclinical and overt hypothyroidism, at present there is no evidence to recommend pharmacological correction of the isolated hyperthyrotropinemia often encountered in obese patients. While thyroid hormones are not indicated as anti-obesity drugs, preclinical studies suggest that thyromimetic drugs, by targeting selected receptors, might be useful in the treatment of obesity and dyslipidemia.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Autoimmunity; Body Weight; Energy Intake; Energy Metabolism; Feedback, Physiological; Feeding Behavior; Humans; Hypothyroidism; Leptin; North America; Obesity; Randomized Controlled Trials as Topic; Thyroid Gland; Thyroid Hormones; Thyroid Neoplasms; Thyroiditis, Autoimmune; Thyrotropin

There is increasing evidence that obesity may have pathophysiological effects that extend beyond its well-known co-morbidities; in particular its role in cancer has received considerable epidemiological support. As adipose tissue becomes strongly established as an endocrine organ, two of its most abundant and most investigated adipokines, leptin and adiponectin, are also taken beyond their traditional roles in energy homeostasis, and are implicated as mediators of the effects of obesity on cancer development. This review examines these adipokines in relation to the prostate, breast, colorectal, thyroid, renal, pancreatic, endometrial and oesophageal cancers, and how they may orchestrate the influence of obesity on the development of these malignancies.

Topics: Adiponectin; Body Mass Index; Breast Neoplasms; Colorectal Neoplasms; Endometrial Neoplasms; Esophageal Neoplasms; Female; Humans; Kidney Neoplasms; Leptin; Male; Neoplasms; Obesity; Pancreatic Neoplasms; Prostatic Neoplasms; Thyroid Neoplasms

Leptin is a multifunctional adipose-derived cytokines that play a critical role in bodyweight homeostasis and energy balance. Recently, leptin and leptin receptor dysreulation have been reported in variety of malignant cells including thyroid. Leptin modulates growth and proliferation of cancer cells via activation of various growth and survival signaling pathways including JAK/STAT, PI3-kinase/AKT and/or Map kinases. In this review, current understanding of leptin's role in the pathogenesis of thyroid cancer has been described.

Topics: Humans; Leptin; Receptors, Leptin; Signal Transduction; Thyroid Neoplasms

Cachexia is the result of complex metabolic alterations which cause morbidity and mortality in patients with advanced cancers including undifferentiated (anaplastic) thyroid carcinoma (ATC). ATC is a lethal disease with limited therapeutic options and unclear etiology for cachexia. We hypothesize that the BRAF(V600E) oncoprotein triggers microvascular endothelial cell tubule formation (in vitro angiogenesis) by means of factors which play a crucial role in angiogenic switch, inflammation/immune response and cachexia. We use human ATC cells and applied multiplex ELISA assay to screen for and measure angiogenic/cachectic and pro-inflammatory factors in the ATC-derived secretome. We find that vemurafenib anti-BRAF(V600E) therapy significantly reduces secreted VEGFA, VEGFC and IL6 protein levels compared to vehicle-treated ATC cells. As a result, the secretome from vemurafenib-treated ATC cells inhibits microvascular endothelial cell-related in vitro angiogenesis. Furthermore, ATC clinical samples express VEGFA, VEGFC and IL6 proteins. Our results suggest that angiogenic/cachectic and pro-inflammatory/immune response factors could play a crucial role in BRAF(V600E)-positive human ATC aggressiveness. Understanding the extent to which microenvironment-associated angiogenic factors participate in cachexia and cancer metabolism in advanced thyroid cancers will reveal new biomarkers and foster novel therapeutic approaches.

Topics: Angiogenic Proteins; Cachexia; Cell Line, Tumor; Cytokines; Humans; Indoles; Inflammation Mediators; Leptin; Mutation; Neovascularization, Pathologic; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Signal Transduction; Sulfonamides; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Tumor Microenvironment; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor C; Vemurafenib

Obesity results in increased secretion of cytokines from adipose tissue and is a risk factor for various cancers. Leptin is largely produced by adipose tissue and cancer cells. It induces cell proliferation and may serve to induce various cancers. OB3-leptin peptide (OB3) is a new class of functional leptin peptide. However, its mitogenic effect has not been determined. In the present study, because of a close link between leptin and the hypothalamic-pituitary-thyroid axis, OB3 was compared with leptin in different thyroid cancer cells for gene expression, proliferation and invasion. Neither agent stimulated cell proliferation. Leptin stimulated cell invasion, but reduced adhesion in anaplastic thyroid cancer cells. Activated ERK1/2 and STAT3 contributed to leptin-induced invasion. In contrast, OB3 did not affect expression of genes involved in proliferation and invasion. In vivo studies in the mouse showed that leptin, but not OB3, significantly increased circulating levels of thyrotropin (TSH), a growth factor for thyroid cancer. In summary, OB3 is a derivative of leptin that importantly lacks the mitogenic effects of leptin on thyroid cancer cells.

Topics: Animals; Carbohydrate Metabolism; Cell Line, Tumor; Cell Proliferation; Disease Progression; Humans; Leptin; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Peptide Fragments; Random Allocation; Signal Transduction; Thyroid Neoplasms; Thyrotropin

Adipokines are bioactive proteins that mediate metabolism, inflammation and angiogenesis. Changes in the secretion of key serum adipokines - adiponectin and letpin - may be associated with obesity, cancer and metabolic disorders. Thyroid cancer is one of the most important types of endocrine cancer. Therefore, investigating the association between serum levels of adiponectin and leptin and thyroid cancer might be important. The purpose of this study was to assess adiponectin and leptin levels in medullary thyroid carcinoma (MTC) cases in order to identify novel tumor markers.. This research was based on a case-control study, including 45 patients with medullary thyroid cancer (21 men and 24 women) and 45 healthy controls (24 males and 21 females). Adiponectin and leptin levels were measured by ELISA in both groups. Height and weight were measured and body mass index (kg/m2) was calculated.. Adiponectin and leptin levels were not significantly different between medullary thyroid carcinomas and the control group. Also, there was no correlation among age and body mass index and the disease.. These results suggest that changes in serum adiponectin and leptin levels do not play an important role in the diagnosis or could act as as biomarkers for medullary thyroid cancer.

Topics: Adiponectin; Adult; Biomarkers, Tumor; Body Mass Index; Body Weight; Carcinoma, Neuroendocrine; Case-Control Studies; Female; Humans; Leptin; Male; Thyroid Neoplasms; Young Adult

To investigate the potential prognostic significance of leptin and its receptor (Ob-R) in thyroid carcinoma.. The study cohort consisted of 173 patients including 93 cases with papillary thyroid carcinoma (PTC), 41 cases with follicular thyroid carcinoma (FTC), 25 cases with medullary thyroid carcinoma (MTC) and 14 cases with anaplastic thyroid carcinoma (ATC). We investigated the correlation between clinicopathological features and leptin or Ob-R. The Kaplan-Meier method was used to analyse the survival rate.. There was a strong correlation of leptin expression with Ob-R expression in PTC, FTC and ATC. For PTC, leptin expression was strongly correlated with older age, larger tumour size, nodal metastasis and advanced stage. Ob-R was significantly correlated with larger tumour size, nodal metastasis and advanced stage. The 5-year disease-free survival (DFS) rate in patients with positive leptin or its receptor expression was lower than that in patients without expression (with statistical difference). For FTC, patients with positive leptin or Ob-R expression developed no recurrence or metastasis during the follow-up. For MTC, Ob-R was significantly correlated with nodal metastasis and advanced stage (P < 0·05). For ATC, patients with positive Ob-R expression had longer median DFS than those with negative expression (436 ± 185 vs 57 ± 71 days), and the difference in the survival rate was statistically significant (P < 0·05).. There was a strong correlation of leptin expression with Ob-R expression in PTC, FTC and ATC. Leptin and Ob-R had negative prognostic significance in PTC, while Ob-R may play a protective role in ATC.

Topics: Adenocarcinoma, Follicular; Carcinoma; Carcinoma, Neuroendocrine; Carcinoma, Papillary; Cohort Studies; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Leptin; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Receptors, Leptin; Recurrence; Survival Rate; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Tissue Array Analysis

Topics: Carcinoma; Female; Humans; Leptin; Male; Thyroid Neoplasms

Topics: Carcinoma; Humans; Leptin; Thyroid Neoplasms

There is a proven relationship between obesity and several cancers including breast, endometrium, colorectal, and esophagus. With the increasing incidence of both obesity and thyroid cancer, we designed the present study to investigate a causal relationship between leptin, which is one of the well known adipokines, and well-differentiated thyroid cancer (WDTC).. Serum leptin levels were measured in 30 patients with WDTC and compared to 30 healthy control subjects before and 1 month after surgery. Other parameters studied included age, sex, body mass index, menopausal status in women, lymph node status, tumor size, and disease multifocality.. There were no differences between the two groups regarding age and sex. Preoperative leptin levels were higher in the WDTC patients when compared to the control patients [19.25 (1.50-109.60) vs 0.90 (0.50-11.80) ng/ml, p < 0.001, group 1 vs group 2, respectively]. A significant drop in leptin levels 1 month after surgery occurred in the WDTC group, falling from 19.25 (1.50-109.60) to 0.90 (0.60-8.90) ng/ml (p < 0.001). This did not occur in the control group (p = 0.274). Lymph node involvement, tumor size, and multifocality had no effect on leptin levels, although trends were observed (p = 0.48, 0.079, and 0.064), respectively.. Serum leptin levels were significantly higher in WDTC patients when compared to control group patients, with a significant drop after surgery. Leptin may play a role in diagnosis of WDTC; however, its prognostic value is still undetermined.

Topics: Adolescent; Adult; Aged; Body Mass Index; Carcinoma; Case-Control Studies; Cell Differentiation; Female; Humans; Leptin; Lymph Node Excision; Male; Middle Aged; Postoperative Period; Preoperative Period; Prognosis; Thyroid Neoplasms; Thyroidectomy; Young Adult

Recent epidemiological studies provide strong evidence suggesting obesity is a risk factor in several cancers, including thyroid cancer. However, the molecular mechanisms by which obesity increases the risk of thyroid cancer are poorly understood. In this study, we evaluated the effect of diet-induced obesity on thyroid carcinogenesis in a mouse model that spontaneously develops thyroid cancer (Thrb(PV/PV)Pten(+/-) mice). These mice harbor a mutated thyroid hormone receptor-β (denoted as PV) and haplodeficiency of the Pten gene. A high-fat diet (HFD) efficiently induced the obese phenotype in Thrb(PV/PV)Pten(+/-) mice after 15 weeks. Thyroid tumor growth was markedly greater and survival was significantly lower in Thrb(PV/PV)Pten(+/-) mice fed an HFD than in controls fed a low-fat diet (LFD). The HFD increased thyroid tumor cell proliferation by increasing the protein levels of cyclin D1 and phosphorylated retinoblastoma protein to propel cell cycle progression. Histopathological analysis showed that the frequency of anaplasia of thyroid cancer was significantly greater (2.6-fold) in the HFD group than the LFD group. The HFD treatment led to an increase in parametrial/epididymal fat pad and elevated serum leptin levels in Thrb(PV/PV)Pten(+/-) mice. Further molecular analyses indicated that the HFD induced more aggressive pathological changes that were mediated by increased activation of the Janus kinase 2-signaling transducer and activator of transcription 3 (STAT3) signaling pathway and induction of STAT3 target gene expression. Our findings demonstrate that diet-induced obesity exacerbates thyroid cancer progression in Thrb(PV/PV)Pten(+/-) mice and suggest that the STAT3 signaling pathway could be tested as a potential target for the treatment of thyroid cancer.

Topics: Animals; bcl-X Protein; Cell Cycle; Cell Proliferation; Cyclin D1; Diet, High-Fat; Disease Models, Animal; Female; Heterozygote; Janus Kinase 2; Leptin; Male; Mice; Mutation; Obesity; Phosphorylation; Proto-Oncogene Proteins c-myc; PTEN Phosphohydrolase; Retinoblastoma Protein; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; STAT3 Transcription Factor; Thyroid Gland; Thyroid Hormone Receptors beta; Thyroid Neoplasms

Obesity is associated with a higher incidence of thyroid cancer. Adiponectin is one of the most abundant adipokines with a pleiotropic role in metabolism and in the development and progression of cancer. It has been shown that circulating adiponectin level is inversely associated with the risk of thyroid cancer. This study aimed to investigate the possible association between the expression of adiponectin receptors (AdipoR1 and AdipoR2) and clinicopathological variables in papillary thyroid cancer. We found that protein levels of AdipoR1 and AdipoR2 were increased in some thyroid cancer specimens compared with adjacent normal thyroid tissues. Thyroid cancer cells expressed AdipoR1 and AdipoR2, which were attenuated by histone deacetylase inhibitors valproic acid and trichostatin A. Adiponectin stimulated AMP-activated protein kinase phosphorylation in thyroid cancer cells. We further determined the expression of AdipoR1 and AdipoR2 by immunohistochemical staining in primary tumor samples and metastatic lymph nodes. AdipoR1 was expressed in 27 % of primary tumors and AdipoR2 in 47 %. Negative expression of both adiponectin receptors was significantly associated with extrathyroidal invasion, multicentricity, and higher TNM stage. There was a trend toward decreased disease-free survival in patients with negative tumor expression of AdipoR1 and AdipoR2 (log-rank P = 0.051). Collectively, overexpression of adiponectin receptors was observed in some tumor tissues of papillary thyroid cancer and was associated with a better prognosis.

Topics: Adiponectin; Adult; AMP-Activated Protein Kinases; Blotting, Western; Carcinoma, Papillary; Cell Line, Tumor; Disease-Free Survival; Female; Humans; Immunohistochemistry; Leptin; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Phosphorylation; Receptors, Adiponectin; Receptors, Leptin; Thyroid Neoplasms

The incidence of thyroid cancer has remarkably increased in recent years. Epidemiologic data suggest that obesity is associated with an increased incidence of several types of malignancies, including thyroid cancer. Leptin, an adipocyte-derived cytokine, has been shown to be involved in cancer development and progression. We previously demonstrated that papillary thyroid cancer expressing leptin receptor and/or leptin has a higher incidence of lymph node metastasis. In this study, we investigated the effects of leptin on cell migration in K1 and B-CPAP papillary thyroid cancer cells. Expression of leptin receptor was observed in both cell lines. Leptin enhanced the migratory activity significantly in a dose-dependent manner. We showed that leptin induced AKT and extracellular signal-regulated kinase (ERK) phosphorylation. Inhibition of phosphatidylinositol 3-kinase and ERK activation using pharmacological inhibitors effectively blocked leptin-induced migration of K1 and B-CPAP cells. Taken together, this study provides new mechanistic evidence for a role of leptin in the regulation of papillary thyroid cancer progression by stimulating tumor cell migration.

Topics: Carcinoma; Carcinoma, Papillary; Cell Line, Tumor; Cell Movement; Extracellular Signal-Regulated MAP Kinases; Humans; Immunohistochemistry; Leptin; MAP Kinase Kinase Kinases; MAP Kinase Signaling System; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Leptin; Signal Transduction; Thyroid Cancer, Papillary; Thyroid Neoplasms

The putative role of leptin and its receptor (Ob-R) in the pathogenesis of various primary human malignancies has been reported; however, their role in papillary thyroid cancer (PTC) has not yet been evaluated. We investigated the role of Ob-R in a large tissue microarray cohort of PTC followed by in vitro studies using a panel of PTC cell lines. Ob-R overexpression was seen in 80% PTCs and was significantly associated with poor disease-free survival (P=0.0235). PTCs that overexpressed Ob-R showed a aggressive phenotype characterized by older age, extrathyroid extension, larger tumor size, nodal metastasis, advanced stage, tall cell variant histological subtype, and a poor disease-free survival (P=0.0005, P=0.0006, P=0.0398, P=0.0004, P=0.0111, P=0.0003, and P=0.0235 respectively). However, Ob-R expression was not an independent prognostic marker to predict disease-free survival in multivariate analysis. PTCs with overexpression of Ob-R showed a significant direct association with overexpression of XIAP (P<0.0001) and Bcl-XL (P<0.0001). In vitro analysis showed that leptin stimulated cell proliferation and inhibited apoptosis via activation of phosphatidylinisitol 3' kinase (PI3K)/protein kinase B (AKT) signaling pathway. Inhibition of PI3K activity by its inhibitor LY294002 abrogated leptin-mediated PI3K/AKT signaling. Gene silencing of Ob-R in PTC cells resulted in downregulation of phospho-AKT, Bcl-XL, and XIAP expression suggesting that leptin-mediated pathogenesis of PTC occurs via involvement of these downstream targets. Altogether, these data show that leptin plays an important role in PTC pathogenesis through PI3K/AKT pathway via Ob-R and is a potential prognostic marker associated with an aggressive phenotype and poor disease-free survival.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Papillary; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Genetic Linkage; Humans; Leptin; Male; Middle Aged; Neoplasm Invasiveness; Oncogene Protein v-akt; Phosphatidylinositol 3-Kinases; Prognosis; Receptors, Leptin; RNA, Small Interfering; Signal Transduction; Thyroid Neoplasms; Tumor Burden; Tumor Cells, Cultured

Epidemiologic studies have shown that obesity is associated with an increased risk of thyroid cancer. Leptin, an adipocyte-derived cytokine, can act as a growth factor on certain normal and transformed cells. Aberrant expression of leptin or leptin receptor has been detected in some types of cancer. The aim of this study is to determine immunohistochemical expression of leptin and leptin receptor in papillary thyroid cancer to investigate the relationship between their expression and clinicopathologic features.. The expression of leptin and leptin receptor was assessed in 49 primary neoplasms and 15 lymph node metastases using a semiquantitative immunohistochemical staining method.. Leptin and leptin receptor were expressed in 37% and 51% of papillary thyroid cancer, respectively. They were not expressed in normal follicles. In the primary neoplasms and the metastatic nodes, expression of leptin correlated closely with leptin receptor (P < .001 for the primary neoplasms and P = .017 for nodal metastases). Expression of either protein was associated with greater neoplasm size (leptin expression, 32.0 +/- 10.7 vs 20.5 +/- 8.4 mm; P = .001; leptin receptor expression, 27.9 +/- 11.5 vs 21.4 +/- 9.0 mm; P = .032). Coexpression of leptin and leptin receptor in primary neoplasms had greater incidence of lymph node metastasis (P = .038).. Expression of leptin and/or leptin receptor in papillary thyroid cancer is associated with neoplasm aggressiveness, including tumor size and lymph node metastasis.

Topics: Adult; Body Mass Index; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Leptin; Lymphatic Metastasis; Male; Middle Aged; Receptors, Leptin; Thyroid Neoplasms

TSH-receptor (TSHR) has been found in a variety of cell types, including preadipocytes and adipocytes. In vitro, TSH-mediated preadipocyte and adipocyte responses include proliferation, differentiation, survival, and lipolysis. Objective To measure the response of serum leptin to exogenous administration of recombinant human TSH (rhTSH) in vivo. Patients One hundred patients with differentiated thyroid cancer already treated by total thyroidectomy and (131)I remnant ablation were enrolled. Mean (+/-s.e.m.) body mass index (BMI) was 26.9+/-0.6 kg/m(2). Methods Patients received a standard dose of rhTSH for measurement of thyroglobulin in the follow-up of their disease. Blood samples were taken for the assay of TSH and leptin before the first administration of rhTSH (time 0), and 24 h (time 1), 48 h (time 2), 72 h (time 3), and 96 h (time 4) after the first administration of rhTSH. Results Significant mean serum leptin increments, with respect to basal value, were 16, 13, 18, and 11% at times 1, 2, 3, and 4 respectively. Significant positive correlations of leptin-area under the curve with respect to basal leptin levels (r=0.43; P<0.0001) and BMI (r=0.32; P<0.005) were observed. Conclusions Acute rhTSH administration in hypothyroid subjects under l-thyroxine therapy produces a rise in serum leptin. This increase is proportional to the adipose mass suggesting that a functioning TSHR is expressed on the surface of adipocytes. The role that TSHR activation in adipocytes might play in physiological and pathological conditions remains a matter of investigation.

Topics: Adolescent; Adult; Aged; Female; Humans; Leptin; Male; Middle Aged; Receptors, Thyrotropin; Thyroid Neoplasms; Thyrotropin; Young Adult

Excess body weight is associated with a moderately increased risk of thyroid cancer. Adipocyte-derived hormone, leptin, has been shown to enhance cell growth and migration in many cancer types. Limited evidence suggests that leptin has direct actions on the thyroid gland, but there are no data available on the effect of leptin on thyroid cancer cells. We evaluated the action of leptin on gene expression, cell growth, cell cycle, and cell migration in anaplastic (ARO), follicular (WRO) and papillary (CGTH-W3) thyroid carcinoma cell lines. Expression of long-form leptin receptors was observed in all thyroid cancer cell lines. Leptin stimulation did not alter the expression levels of leptin, leptin receptor and sodium-iodide symporter. Cell growth and cell cycle were not changed after leptin treatment. However, leptin was able to promote cell migration of papillary thyroid cancer cells, but inhibited migration of anaplastic and follicular cancer cells. In summary, our study suggests that leptin modulates cell migration of thyroid cancer cells in a cell type-specific manner.

Topics: Adenocarcinoma, Follicular; Apoptosis; Blotting, Western; Carcinoma; Carcinoma, Papillary; Cell Cycle; Cell Movement; Cell Proliferation; Humans; Leptin; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thyroid Neoplasms

Topics: Adult; Body Mass Index; Carcinoma; Child, Preschool; Fasting; Humans; Hypothyroidism; Insulin; Leptin; Obesity; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triglycerides; Triiodothyronine; Weight Loss

Leptin has physiological roles in multiple systems, and has possible effects on several carcinogenesis steps. The aim of this study was to investigate the leptin levels in thyroid papillary carcinoma (TPC) patients.. Forty-three female TPC patients and 30 healthy female control subjects were recruited for the study. TPC was diagnosed by fine needle aspiration biopsy. TPC patients had a bilateral total thyroidectomy operation and their leptin levels were measured before and 20 days after the operation.. Serum leptin levels of TPC patients were higher than in control group subjects (21.15 +/- 14.12 ng/mL vs. 9.89 +/- 0.21 ng/mL, p < 0.05). The leptin levels decreased after total thyroidectomy (13.92 +/- 10.55 ng/mL) compared to prethyroidectomy levels (22.94 +/- 14.67 ng/mL) in 34 patients who came to the follow-up visit (p < 0.05). However, the decreased post-thyroidectomy levels of leptin were still statistically significantly higher than the control group levels. Multivariate regression analysis showed that the leptin levels in TPC patients were not related to age, menopausal status or pathologic occult status but were directly related to the cancer group.. Leptin levels were elevated in thyroid cancer, decreased after total thyroidectomy, and might be associated with thyroid papillary carcinogenesis.

Topics: Adult; Carcinoma, Papillary; Female; Humans; Leptin; Thyroid Neoplasms; Thyroidectomy

Some extra-thyroid effects of TSH have been described in vitro and in vivo. TSH has recently been suggested to induce interleukin-6 secretion by adipocytes. Leptin is the main protein secreted by adipose tissue.. The aim of our study was to evaluate the acute effect of the recombinant human TSH (rhTSH)-induced TSH surge on serum leptin levels in thyroidectomized patients undergoing levothyroxine (L-T4) suppressive therapy for differentiated thyroid carcinoma (DTC).. A cohort of 15 female DTC patients was evaluated. Standard rhTSH testing was performed. Leptin, TSH, thyroid hormones, and thyroglobulin were measured before and 3, 6, and 9 days after rhTSH testing. Some metabolic parameters were also evaluated at the baseline.. Baseline leptin levels were 12.2+/-3.2 microg/l. Only body mass index (BMI) correlated significantly (p<0.05) with leptin levels. After rhTSH administration, TSH levels increased significantly (p<0.001), while thyroid hormones remained unchanged. Twenty hours after the last rhTSH administration, leptin (11.8+/-3.0 microg/l) levels were unchanged. The maximal TSH level was negatively related with BMI (p<0.05), but no correlation between maximal TSH and leptin levels after rhTSH was noted.. Our in vivo experimental model suggests that an acute TSH increase after rhTSH testing is ineffective in changing circulating leptin levels.

Topics: Adult; Aged; Carcinoma; Female; Humans; Leptin; Middle Aged; Recombinant Proteins; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Thyroxine

Previous studies addressing the influence of thyroid hormones on serum levels of adipokines yielded conflicting results. We aimed to study the impact of short-term overt hypothyroidism on serum leptin, resistin, and adiponectin levels in an in vivo human model.. Twenty-two women with differentiated thyroid carcinoma were studied the last day of their thyroxine-suppressive treatment, 4-7 days after withdrawal, and the day before whole-body scanning. Evaluations included serum thyroid hormone, leptin, resistin, and adiponectin concentrations, fasting glucose and insulin, lipid profiles, body temperature, body mass index, and total body fat mass.. Thyroid function changed from subclinical or mild hyperthyroidism to normal free thyroxine and triiodothyronine levels, ending in overt hypothyroidism. Thyroxine withdrawal resulted in an increase in serum resistin (p = 0.007) and leptin (p = 0.006) concentrations, whereas adiponectin levels remain unchanged. A significant decrease in body temperature during thyroxine withdrawal was paralleled by a decrease in fasting glucose (p = 0.006) and insulin resistance (p = 0.033), which occurred despite an increase in estimated total body fat mass.. Thyroid hormones are important regulators of energy balance and intermediate metabolism, influencing the serum concentrations of leptin and resistin.

Topics: Adiponectin; Adult; Blood Glucose; Female; Humans; Leptin; Middle Aged; Resistin; Substance Withdrawal Syndrome; Thyroid Function Tests; Thyroid Hormones; Thyroid Neoplasms; Thyroxine; Whole Body Imaging

Leptin, a recently discovered protein produced in adipocytes, regulates body weight by suppressing food intake and/or increasing energy expenditure. Thyroid hormones, which increase the basal metabolic rate and thermogenesis, have been reported to be one of leptin's regulating factors because alternations in thyroid status might lead to compensatory changes in circulating leptin.. The aim of this study was to assess the influence of sequential changes in thyroid function on serum leptin levels.. The thyroid function status of 65 patients (55 women and 10 men, aged 40.6 +/- 15.2 years, mean +/- SD) with differentiated thyroid cancer who had received near-total thyroidectomy was studied before I-131 ablation therapy and after 2-4 and 6 months of levo-thyroxine suppressive therapy. Thirty-three (26 women, seven men; aged 41.0 +/- 10.4 years, mean +/- SD) of them were found to have become hypothyroid, then euthyroid and subsequently subclinically hyperthyroid. Their body mass index (BMI), body fat (%BF) by electrical bioimpedance, thyroid function and fasting serum leptin in these states were assessed and compared to those of 38 controls (30 women, eight men, aged 40.2 +/- 11.3 years, mean +/- SD). The controls had no past history or family history of thyroid diseases, and had the same range of BMI, between 20 and 30 kg/m2, as the patients.. No difference in serum leptin levels was found between patients and controls with comparable age, sex, and BMI distribution in the euthyroid state. Using a repeated measures anova, tests of TSH, free T4 (FT4), BMI,%BF and leptin were performed on the 33 patients with sex as a grouping factor and thyroid state as a time factor. The sex difference for %BF and leptin proved to be statistically significant (P < 0.0001, and P = 0.0003, respectively). Serum leptin levels increased significantly from the hypothyroid to the subclinical hyperthyroid state (P < 0.0001) with a more pronounced increase found in females than in males (P = 0.03). Change of BMI during sequential thyroid function alterations was significant (P = 0.04) while change in %BF was not significant (P = 0.09). Pearson correlation analysis showed that serum leptin levels significantly correlated with BMI, %BF, FT4, and TSH (all P < 0.05). Using the generalized estimating equations, multivariate regression analysis revealed that FT4 was a statistically independent predictor for serum leptin (P < 0.0001). While other parameters were held constant, the mean serum leptin level increased by 1.47 units when serum FT4 was increased by one unit.. In conclusion, our data indicate that circulating thyroid hormone plays a relevant role in regulating leptin metabolism independent of BMI and body fat.

Topics: Adult; Analysis of Variance; Body Composition; Body Mass Index; Case-Control Studies; Female; Humans; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Leptin; Male; Middle Aged; Sex Factors; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Thyroxine

The aim of the study is to determine the effect of short-term hypothyroidism on serum leptin levels. For this purpose 30 patients with past medical history of thyroidectomy for differentiated thyroid carcinoma were included. Serum leptin concentrations were similar when patients were on thyrotrophin-suppressive thyroxine therapy than when were admitted 4 weeks after stopping thyroxine treatment to perform a routine 131I scan in hypothyroid status (17.0 +/- s.e.m. 2.14 vs. 17.6 +/- s.e.m. 2.41 ng/ml; p = n.s.). Moreover, no differences were obtained when the analysis was performed separately in men and in women. We conclude that short-term hypothyroidism does not alter serum leptin concentrations. Furthermore, our results suggest that thyroid hormones do not operate through changes in serum leptin levels to regulate energy expenditure.

Topics: Female; Humans; Hypothyroidism; Leptin; Male; Middle Aged; Sex Characteristics; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Thyroxine; Time Factors