Impact of Nutritional Status of Patients with Head and Neck Squamous Cell Carcinoma on the Expression Profile of Ghrelin, Irisin, and Titin.

The goal of this paper was the evaluation of the changes in the expression profile of irisin, ghrelin, and titin in the carcinoma tissue and in the blood of patients with head and neck squamous cell carcinoma (HNSCC), including determining the profile of their expression in relation to patient nutrition. The study included 56 patients with diagnosed squamous cell carcinoma of HNSCC in the T3 and T4 stages of the disease. Healthy control tissue specimens were collected from an area 10 mm outside the histologically negative margin. In turn, the blood and serum from the control group came from healthy volunteers treated for non-oncologic reasons (n = 70). The molecular analysis allowed us to determine the profile of irisin, ghrelin, and titin methylation, evaluate their expression on the level of mRNA (quantitative Reverse Transcription Polymerase Chain Reaction; qRT-PCR) and protein (Enzyme-Linked Immunosorbent Assay Reaction; ELISA) in the carcinoma tissue and the margin of healthy tissue, as well as in serum of patients in the study and control groups. At the start of our observations, a Body Mass Index (BMI) < 18.5 was noted in 42 of the patients, while six months after the treatment a BMI < 18.5 was noted in 29 patients. We also noted a decrease in the expression of irisin, ghrelin, and titin both on the level of mRNA and protein, as well as a potential regulation of their expression via DNA methylation. There is no convincing evidence that the proteins assayed in the present work are specific with regard to HNSSC.

ATPase Inhibitory Factor 1-A Novel Marker of Cellular Fitness and Exercise Capacity?

ATPase inhibitory factor 1 is a myokine inhibiting the hydrolytic activity of mitochondrial adenosine triphosphate synthase and ecto-F1-ATPase on the surface of many cells. IF1 affects ATP metabolism in mitochondria and the extracellular space and upregulates glucose uptake in myocytes; these processes are essential in physical activity. It is unknown whether the IF1 serum concentration is associated with exercise capacity. This study explored the association between resting IF1 serum concentration and exercise capacity indices in healthy people. IF1 serum concentration was measured in samples collected at rest in 97 healthy amateur cyclists. Exercise capacity was assessed on a bike ergometer at the successive stages of the progressive cardiopulmonary exercise test (CPET). IF1 serum concentration was negatively and significantly correlated with oxygen consumption, oxygen pulse, and load at various CPET stages. A better exercise capacity was associated with lower circulating IF1. IF1 may reflect better cellular/mitochondrial energetic fitness, but there is uncertainty regarding how IF1 is released into the intravascular space. We speculate that lower IF1 concentration may reflect a better cellular/mitochondrial integrity, as this protein is bound more strongly with ATPases in mitochondria and cellular surfaces in people with higher exercise capacity.

The Role of Thyroid Hormones on Skeletal Muscle Thermogenesis.

Nowadays obesity becomes a significant global problem. Hence, recently more and more attention has been paid to substances present in the body that have a significant impact on metabolic processes and thermogenesis, in the context of their potential use in the prevention and treatment of obesity. It is well known that the relationship between thyroid hormones and obesity is multilayered, however recently, more and more information about the possible relation between thyroid hormones and muscle metabolism has been published. The aim of this review is to present the most updated information on the physiological impact of thyroid hormones on muscle tissue, as well as pathological changes related to the occurrence of various types of thyroid disorders, including hypothyroidism, hyperthyroidism and sick euthyroid syndrome. However, the data in humans still remains insufficient, and further studies are needed to fully explore the thyroid-muscle cross-talk.

Effect of restoration of euthyroidism on visfatin concentrations and body composition in women.

Dysregulation of thyroid function has known impact on body metabolism, however, data regarding metabolic outcome after restoration of thyroid function is limited. Therefore, the aim of the study was to investigate the effect of restoration of euthyroidism on serum visfatin, and its associations with insulin resistance and body composition. This is an observational study with consecutive enrollment. Forty-nine hyperthyroid (median age of 34 years) and 44 hypothyroid women (median age of 46 years) completed the study. Laboratory parameters and body composition analysis were assessed before and after the therapy. In the hyperthyroid group, visfatin concentrations increased (P < 0.0001), while glucose concentrations decreased (P < 0.0001). Total body mass and fat mass in the trunk and limbs significantly increased during the treatment. In the hypothyroid group, significant weight loss resulted from decrease of fat and muscle masses in trunk and limbs. Visfatin serum concentrations positively correlated with total fat mass (r = 0.19, P = 0.01) and insulin concentrations (r = 0.17, P = 0.018). In conclusion, restoration of thyroid function is not associated with beneficial changes in body composition, especially among hyperthyroid females.

Effect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People.

Different forms of physical activity-endurance, resistance or dynamic power-stimulate cytokine release from various tissues to the bloodstream. Receptors for exercise-induced cytokines are present in muscle tissue, adipose tissue, liver, brain, bones, cardiovascular system, immune system, pancreas, and skin. They have autocrine, paracrine and endocrine activities. Many of them regulate the myocyte growth and differentiation necessary for muscle hypertrophy and myogenesis. They also modify energy homeostasis, lipid, carbohydrate, and protein metabolism, regulate inflammation and exchange information (crosstalk) between remote organs. So far, interleukin 6 and irisin have been the best studied exercise-induced cytokines. However, many more can be grouped into myokines, hepatokines and adipomyokines. This review focuses on the less known exercise-induced cytokines such as myostatin, follistatin, decorin, brain-derived neurotrophic factor, fibroblast growth factor 21 and interleukin 15, and their relation to various forms of exercise, i.e., acute vs. chronic, regular training in healthy people.

Titin and dystrophin serum concentration changes in patients affected by thyroid disorders.

INTRODUCTION: It is well established that thyroid hormones significantly affect skeletal muscle function, causing symptoms like myalgia and muscle weakness. Hypothyroid patients present increased levels of creatine kinase (CK), indicating muscle destruction. Lately, we proposed new serum markers of muscle disturbances in thyroid disorders: titin (TTN) and dystrophin (DMD). The aim of this study is to determine the association between thyroid status, muscle metabolism, and serum levels of TTN and DMD in patients affected by hypoand hyperthyroidism, before and after the treatment. MATERIAL AND METHODS: In the study 56 subjects were enrolled. The studied group consisted of 16 patients with newly diagnosed overt hypothyroidism and 20 patients with hyperthyroidism. Twenty healthy controls were also included in the study. Body composition, thyroid hormones, and biochemical markers of muscle deterioration levels were evaluated before and after restoration of euthyroidism. RESULTS: Dystrophin and TTN levels were noticeably lower in the hypothyroid group and hyperthyroid group in comparison with controls, at the border of statistical significance. Along with the thyroid hormones and CK normalisation, DMD levels increased in the hypothyroid group, with no significant lowering of TTN levels. However, TTN concentrations and the fT3/fT4 ratio became significantly lower than in controls. Hyperthyroid patients experienced no significant changes in TTN and DMD. CONCLUSIONS: The presented data indicate that TTN and DMD are potential new markers of musculoskeletal deterioration in thyroid disorders. In addition, the shift in TTN and DMD serum concentrations after the treatment of hypothyroidism accompanied by decreased fT3/fT4 ratio suggest the influence of the chosen therapeutic approach on muscle metabolism.

Does nesfatin-1 influence the hypothalamic-pituitary-gonadal axis in adult males with obstructive sleep apnoea?

There is growing evidence that obstructive sleep apnoea (OSA) influences the hypothalamic-pituitary-gonadal axis (HPG axis) in men. The aim of the study was to assess the association of nesfatin-1 with HPG axis disturbances in OSA. This is a prospective study with consecutive enrolment. It comprises 72 newly diagnosed OSA patients ((AHI: apnoea-hypopnea index) 18 subjects: 5 ≤ AHI < 15; 24: 15 ≤ AHI < 30; 30: AHI ≥ 30) and a control group composed of 19 patients (AHI < 5). All patients underwent polysomnography and fasting blood collection for nesfatin-1, testosterone, luteinising hormone (LH), high-sensitivity C-reactive protein (hsCRP), aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine and glucose. Groups had similar levels of LH, nesfatin-1 and testosterone (p = 0.87; p = 0.24; p = 0.08). Nesfatin-1 was not correlated to LH (p = 0.71), testosterone (p = 0.38), AHI (p = 0.34) or the oxygen desaturation index (ODI) (p = 0.69) either in the whole group, or in sub-groups. The study did not reveal any association between the HPG axis and nesfatin-1 in OSA adult males. It is possible that nesfatin-1 is not a mediator of HPG axis disturbances in adult patients with OSA.

Determinants of Visfatin/NAMPT Serum Concentration and its Leukocyte Expression in Hyperthyroidism.

We aimed to analyze the potential influence of thyroid autoimmunity on visfatin/NAMPT serum concentration and its leukocyte expression in hyperthyroid patients. This is a single-center, cross-sectional study with consecutive enrollment. All patients with newly diagnosed overt hyperthyroidism in a course of Graves' disease or toxic nodular goiter were included in the study. They underwent physical examination, laboratory investigation, body composition analysis, and thyroid ultrasound. NAMPT mRNA leukocyte expressions were measured using RT-qPCR. Of the 173 patients, 95 were enrolled in further analysis [67 patients with Graves' disease (GD) and 28 with toxic nodular goiter (TNG)]. Control group consisted of 43 healthy volunteers adjusted for age, sex, and BMI. Higher NAMPT/visfatin serum concentration was found in patients with GD comparing with patients with TNG (p=0.03855). We found significant NAMPT leukocyte overexpression in GD patients (n=32) as compared to TNG patients (n=18) and euthyroid controls (n=24) (p=0.005965). Simple linear regression analysis revealed that NAMPT/visfatin serum concentration was significantly associated with NAMPT leukocyte expression, thyroid autoimmunity, age, HOMA-IR, and fat mass percentage (FM%). NAMPT leukocyte expression was related to thyroid autoimmunity, age, and TRAb levels. The stepwise multiple regression analysis revealed FM% and HOMA-IR as independent predictors of visfatin/NAMPT serum levels. In a separate stepwise multiple regression analysis, we confirmed the association between NAMPT leukocyte expression and TRAb levels. We found that fat mass percentage together with HOMA-IR are the most significant predictors of visfatin/NAMPT serum elevation in hyperthyroid patients.

Red cell distribution width - a new marker for exacerbation of heart failure in patients with hypothyroidism following radioiodine therapy.

INTRODUCTION: Cardiovascular diseases constitute a major cause of health problems and death in developed countries across the world. The increased value of the index of distribution of red blood cells volume (RDW) may be a prognostic marker in patients diagnosed with chronic heart failure (CHF). Hypothyroid patients present higher RDW values if compared to healthy controls. Taking into consideration that RDW might be both affected by thyroid status and CHF, we decided to determine the effect of concomitant hypothyroidism following radioiodine therapy (RIT) and CHF on hematological parameters. MATERIALS AND METHODS: Patients with toxic nodular goiter and heart failure with concomitant anemia were included. Patients underwent treatment with radioiodine before the planned heart transplant or pacemaker implantation (combined ICD/CRT-D). After RIT patients were divided into the three subgroups: with overt hypothyroidism (TSH ≥ 10µIU/mL, Group I), subclinically hypothyroid patients (TSH 4.3-9.0 µIU/mL, Group II) and with high-normal level of TSH (2.6-4.2 µIU/mL, Group III). RESULTS: Significant correlation between TSH and RDW was observed (r=0.46; P < 0.0001) after RIT, whereas no correlation between serum TSH levels and TIBC and Fe was observed. In Group I significant correlation between TSH and RDW (r= 0.48; P = 0.002) after RIT was observed, whereas in two other subgroups there were no significant correlation. CONCLUSIONS: Subclinical hypothyroidism or high-normal levels of TSH did not affect RDW in a significant manner in the studied population. Our results demonstrates that overt hypothyroidism may contribute to deterioration of CHF reflected in changes of RDW value. < p > < /p >.

The association between irisin and muscle metabolism in different thyroid disorders.

BACKGROUND: Irisin is a new adipo-myokine, encoded by the FNDC5 gene. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This prospective study assesses the influence of thyrometabolic changes on serum irisin concentration in association with altered muscle metabolism. This is performed on a large cohort of patients affected by severe hypo- or hyperthyroidism, as well as by the expression of the FNDC5 gene in thyroid tissue affected by different pathologies. METHODS: The study group comprised 119 patients with newly diagnosed severe hyperthyroidism or hypothyroidism, and a control group of 45 healthy subjects. Body composition, serum irisin concentrations, and thyroid-related hormones, creatine kinase, dystrophin and titin concentrations were evaluated. FNDC5 expression was also analysed in tissue samples from 80 patients with nontoxic multinodular goitre, toxic goitre, Graves' disease and papillary thyroid cancer. RESULTS: Irisin concentration was lower in patients with prolonged hypothyroidism. There was a tendency towards lower dystrophin and titin concentrations in patients with hypothyroidism and hyperthyroidism. Restoration of euthyroidism in patients with hypothyroidism resulted in a decreased muscle mass with an increase in irisin concentrations, while the hyperthyroid group showed an increase in fat mass. Statistically significant overexpression of FNDC5 gene was found in patients with toxic goitre as compared to Graves' disease, papillary thyroid cancer and controls. CONCLUSIONS: The presented data support the theory that irisin concentration changes are associated with prolonged hypothyroidism and might primarily constitute the result of prolonged myopathy. These changes are most likely not related to the expression of the FNDC5 gene in the thyroid gland.

Association between bone remodeling and inflammatory markers in obstructive sleep apnea in relation to disease severity.

INTRODUCTION    There is growing evidence that obstructive sleep apnea (OSA) influences both bone metabolism and structure. Chitinase­3­like protein 1 (YKL­40) is a novel inflammatory and remodeling marker, the levels of which were shown to increase in OSA. YKL­40 can probably alter the bone turnover. OBJECTIVES    The aim of the study was to assess a possible interplay between YKL­40 and bone turnover markers in patients with different stages of OSA, and to evaluate the relation between bone mass, severity of OSA, and YKL­40 levels. PATIENTS AND METHODS    The study involved 72 male patients with OSA. They were divided into 3 groups according to disease severity, using the apnea-hypopnea index (AHI): group 1 (n = 18; 5≤ AHI <15), group 2 (n = 25; 15≤ AHI <30), and group 3 (n = 29; AHI ≥30). All patients underwent polysomnography and densitometry. Fasting blood samples were collected for YKL­40, C­terminal telopeptide of typeI collagen (CTX), procollagen type 1 N­terminal propeptide (P1NP), and other markers. RESULTS    P1NP differed between groups 1 and 2, as well as groups 1 and 3 (P = 0.02). Group 2 had higher CTX levels than group 1 (borderline significance, P = 0.05). A simple linear regression analysis showed that serum YKL­40 levels were associated with the levels of CTX (P <0.0001, ß = 0.9871) and P1NP (P <0.0001, ß = 0.9780). CONCLUSIONS    Our study might suggest that YKL­40 is associated with bone turnover in OSA. We may assume that this marker influences both bone formation and destruction; thus, OSA could be characterized by preserved bone mineral density.

Thyroid Hemiagenesis: Incidence, Clinical Significance, and Genetic Background.

Context: Thyroid hemiagenesis (THA) constitutes a rare, congenital disorder that is characterized by an absence of one thyroid lobe. Because the pathogenesis and clinical significance of this malformation remain undefined, specific clinical recommendations are lacking, especially for asymptomatic cases. Evidence Acquisition: The PubMed database was searched (years 1970 to 2017), and the following terms were used to retrieve the results: "thyroid hemiagenesis," "thyroid hemiaplasia," "one thyroid lobe agenesis," and "one thyroid lobe aplasia." Subsequently, reference sections of the retrieved articles were searched. Evidence Synthesis: There is a noticeable susceptibility of subjects with THA to develop additional thyroid and nonthyroidal pathologies. In pathogenesis of concomitant thyroid pathologies, a chronic elevation in thyroid-stimulating hormone values may play an important role. Thus far, genetic studies failed to find a common genetic background of the anomaly, and the potential underlying cause was identified in a minority of the cases. Conclusions: Patients with THA are prone to develop additional thyroid pathologies and theoretically might benefit from l-thyroxine treatment to lower the thyrotropin levels to those observed in the normal population. However, further research should be done to ascertain whether such intervention early in life would prevent development of associated thyroid conditions. At least, increased vigilance should be maintained to reveal all of the concomitant disorders as soon as possible during follow-up examinations. Application of high-throughput technologies enabling a genome-wide search for novel factors involved in thyroid embryogenesis might be the next step to expand the knowledge on THA pathogenesis.

Does TSH Trigger the Anti-thyroid Autoimmune Processes? Observation on a Large Cohort of Naive Patients with Thyroid Hemiagenesis.

Thyroid hemiagenesis (THA) is a rare abnormality characterized by the absence of one thyroid lobe. Elevated thyroid stimulating hormone (TSH) level and higher incidence of thyroid diseases were reported in THA. The aim of the study is to evaluate the thyroid autoimmunity incidence in patients with THA and influence of higher than average TSH level on thyroid volume (TV) and its change with age. The study included a group of naive patients with THA and a control group of subjects with bilobate thyroid. All patients underwent clinical examination, thyroid ultrasound, scintiscan and laboratory tests. In the studied and control group the presence of thyroid autoantibodies (TAb) was evaluated. The THA group consisted of 65 patients. In THA group 53.85 % of patients were positive for TAb. Patients with positive TAb were older (46.0 ± 18.3 years) than those with negative (35.0 ± 19.8 years); p = 0.02. The incidence of TAb was lower in controls (13.85 %, p < 0.0001). In the study group, positive correlation between the age and TV (r = 0.46, p = 0.0001), and negative correlations between the age and TSH level (r = -0.31, p = 0.01), and TSH concentration and TV (r = -0.35, p = 0.004) were found. In a subgroup of 30 patients with THA negative for TAb, even stronger correlations were observed. The median single lobe volume and median TSH level were higher in patients with THA when compared to controls (13.60 vs 8.20 ml, p < 0.0001; 3.23 vs 1.48 µU/ml, p < 0.0001, respectively). Patients with THA constitute an in vivo model of long-term thyroid TSH overstimulation. Further studies are needed to reveal, whether TSH overstimulation may be the trigger for thyroid autoimmunity.

Electrocardiographic and scintigraphic evaluation of patients with subclinical hyperthyroidism during workout.

Subclinical hyperthyroidism (sHT) was found to be associated with elevated heart rate, blood pressure and increased risk of extrasystoles. However, the full clinical relevance of morphological and functional implications of sHT on the cardiovascular system is still a matter of debate. The aim of the study was to prospectively assess the influence of endogenous sHT on exercise capacity and cardiac function during workout with the use of exercise electrocardiography (ExECG) and perfusion scintigraphy. The studied group consisted of 44 consecutively recruited patients diagnosed with sHT. In all patients, ExECG, followed by post-exercise myocardial perfusion imaging, was performed. Both ExECG and scintigraphy were performed twice-in the state of sHT and after euthyroidism was restored. An average time period of exercise test was significantly longer in the state of euthyroidism than in sHT. An average oxygen consumption during exercise test was also higher after euthyroidism was achieved when compared to sHT. The end-diastolic and end-systolic volume indexes, stroke volume index and cardiac index were significantly larger in patients with sHT if compared values achieved after euthyroidism restoration. Stroke volume index was negatively correlated with TSH, and positively with free thyroid hormones values in the state of sHT, before euthyroidism was achieved. Cardiac index was positively correlated with free thyroid hormones levels. The obtained results indicate worse physical capacity in subjects with sHT and improvement of several parameters assessed during ExECG and perfusion scintiscan after therapy. Observed changes might reflect the mechanism of the deleterious effect exerted by sHT on the heart.

Circulating Visfatin in Hypothyroidism Is Associated with Free Thyroid Hormones and Antithyroperoxidase Antibodies.

We hypothesized that regulation of visfatin in hypothyroidism might be altered by coexisting chronic autoimmune thyroiditis. This is a prospective case-control study of 118 subjects. The autoimmune study group (AIT) consisted of 39 patients newly diagnosed with hypothyroidism in a course of chronic autoimmune thyroiditis. The nonautoimmune study group (TT) consisted of 40 patients thyroidectomized due to the differentiated thyroid cancer staged pT1. The control group comprised 39 healthy volunteers adjusted for age, sex, and BMI with normal thyroid function and negative thyroid antibodies. Exclusion criteria consisted of other autoimmune diseases, active neoplastic disease, diabetes mellitus, and infection, which were reported to alter visfatin level. Fasting blood samples were taken for visfatin, TSH, free thyroxine (FT4), free triiodothyronine (FT3), antithyroperoxidase antibodies (TPOAb), antithyroglobulin antibodies (TgAb), glucose, and insulin levels. The highest visfatin serum concentration was in AIT group, and healthy controls had visfatin level higher than TT (p = 0.0001). Simple linear regression analysis revealed that visfatin serum concentration was significantly associated with autoimmunity (ß = 0.1014; p = 0.003), FT4 (ß = 0.05412; p = 0.048), FT3 (ß = 0.05242; p = 0.038), and TPOAb (ß = 0.0002; p = 0.0025), and the relationships were further confirmed in the multivariate regression analysis.

Time-dependent irisin concentration changes in patients affected by overt hypothyroidism.

INTRODUCTION: Irisin, a cleaved and secreted part of the transmembrane protein FNDC5, is a recently discovered adipo-myokine that is said to have a significant influence on body metabolism. Changes in thyrometabolic state may also alter the serum irisin level. Since already reported data are not fully consistent, the aim of the present research is to evaluate the time-dependent changes in serum irisin level in patients affected by overt hypothyroidism. MATERIAL AND METHODS: The study involved 36 subjects - two groups of 12 patients with long-lasting (AITD) and short-term (TC) overt hypothyroidism, and a control group (CG) of 12 subjects, matched for age and gender. Serum irisin level, thyrometabolic state, creatine kinase (CK - muscle damage marker), glucose, and insulin concentration were assessed and compared between groups. RESULTS: The irisin level was significantly lower in AITD than in TC and CG (p = 0.02; p < 0.01; respectively) patients, with no statistical difference between TC and CG (p > 0.05). There was no significant difference between free triiodothyronine and free thyroxine levels in AITD and TC patients (p > 0.05). CK concentration was significantly higher in AITD than in CG patients (p < 0.01) with no difference between AITD and TC patients (p > 0.05) as well as TC and CG patients (p > 0.05). Additionally, the CK level negatively correlated with the irisin level (r = -0.58; p < 0.01). CONCLUSIONS: In conclusion, the irisin concentration changes during thyroid function impairment may be time-dependent. Patients with prolonged hypothyroidism have lower irisin levels that those with short-term disorder. (Endokrynol Pol 2016; 67 (5): 476-480).

Nicotinamide phosphoribosyltransferase leukocyte overexpression in Graves' opthalmopathy.

To investigate the role of NAMPT/visfatin in euthyroid patients with Graves' disease without (GD) and with Graves' ophthalmopathy (GO), we analyzed NAMPT leukocyte expression and its serum concentration. This was a single-center, cross-sectional study with consecutive enrollment. In total, 149 patients diagnosed with Graves' disease were enrolled in the study. We excluded subjects with hyper- or hypothyroidism, diabetes mellitus, other autoimmune disorders, active neoplastic disease, and infection. The control group was recruited among healthy volunteers adjusted for age, sex, and BMI with normal thyroid function and negative thyroid antibodies. Serum levels of visfatin, TSH, FT4, FT3, antibodies against TSH receptor (TRAb), antithyroperoxidase antibodies, antithyroglobulin antibodies, fasting glucose, and insulin were measured. NAMPT mRNA leukocyte expression was assessed using RT-qPCR. NAMPT/visfatin serum concentration was higher in GD (n = 44) and GO (n = 49) patients than in the control group (n = 40) (p = 0.0275). NAMPT leukocyte expression was higher in patients with GO (n = 30) than in GD patients (n = 27) and the control group (n = 29) (p < 0.0001). Simple linear regression analysis revealed that NAMPT/visfatin serum concentration was significantly associated with GD (ß = 1.5723; p = 0.021). When NAMPT leukocyte expression was used as a dependent variable, simple regression analysis found association with TRAb, fasting insulin level, HOMA-IR, GD, and GO. In the stepwise multiple regression analysis, we confirmed the association between higher serum NAMPT/visfatin level and GD (coefficient = 1.5723; p = 0.0212), and between NAMPT leukocyte expression and GO (coefficient = 2.4619; p = 0.0001) and TRAb (coefficient = 0.08742; p = 0.006). Increased NAMPT leukocyte expression in patients with GO might suggest a presently undefined role in the pathogenesis of GO.