Thyroid Diseases and Intestinal Microbiome.

The human microbiome plays an integral role in health. In particular, it is important for the development, differentiation, and maturation of the immune system, 70% of which resides in the intestinal mucosa. Microbiome studies conducted to date have revealed an association between disturbances in the microbiota (dysbiosis) and various pathological disorders, including changes in host immune status. Autoimmune thyroid diseases are one of the most common organ-specific autoimmune disorders, with a worldwide prevalence higher than 5%. The predominant autoimmune thyroid diseases are Hashimoto's thyroiditis and Grave's disease. Several factors, such as genetic and environmental ones, have been studied. In accordance with recent studies, it is assumed that the gut microbiome might play a significant role in triggering autoimmune diseases of the thyroid gland. However, the exact etiology has not yet been elucidated. The present review aims to describe the work carried out so far regarding the role of gut microflora in the pathogenesis of autoimmune thyroid diseases and its involvement in the appearance of benign nodules and papillary thyroid cancer. It appears that future work is needed to elucidate more precisely the mechanism for gut microbiota involvement in the development of autoimmune thyroid diseases.

Divergent Patterns of Thyrotropin and Other Thyroidal Parameters in Relationship with the Sex of Healthy Neonates and Infants Less than Two Years Old: A Longitudinal Study.

Background: A longitudinal study was conducted in full-term healthy infants who were born between 2015 and 2017 in Athens, Greece, to elucidate the evolution of thyrotropin (TSH) and other thyroidal parameters according to sex, from their day of birth until two years old. Other thyroidal parameters that were taken into account include antithyroid peroxidase antibody (TPO-Ab) and antithyroglobulin antibody (TG-Ab), total triiodothyronine (T3), and free triiodothyronine (fT3), along with total thyroxine (T4) and free thyroxine (fT4). Methods: Blood samples were taken at 5-day intervals from the day of birth until the 31st day of life, and then every 5th month until 2 years of age. All thyroid parameters were measured by electrochemiluminescence immunoassays. The study took place at the Iaso General, Maternity and Gynecological Clinic in Athens, Greece. Results: The sample consisted of 2916 full-term healthy neonates/infants: 1507 (51.7%) boys and 1409 (48.3%) girls. There were no significant differences in TSH levels between boys and girls in all time periods from birth up to 2 years except between 11 and 15 months of age (p = 0.038). Mean TSH levels for boys exhibited much more fluctuation and variability than for girls. In boys we found a significant association between TSH levels and fT4 (p < 0.001), while we found a significant association between TSH levels and T3 in girls (p = 0.045). Furthermore, we found that mean TPO-Ab and TG-Ab levels for boys exhibited larger variability than those for girls. Conclusions: In this study, we were able to plot the development of TSH and other thyroidal parameters by sex from birth up to two years of age. In terms of clinical practice, our findings suggest the need for a re-evaluation of the reference ranges of the studied parameters according to sex, especially in the first months of life and until the first year. Furthermore, our results suggest new optimal ranges for thyroid hormone replacement for that specific period.

Therapeutic Challenges in Neuroendocrine Tumors.

Neuroendocrine tumors (NETs) are a diverse set of tumors, being genetically varied. NETs can be presented with a distinct clinical picture, due to the production of various hormones, or being silent. Based on community health clinical statistics, the frequency numbers and reported occurrence of NETs are increasing. Although the therapeutic options for NETs have expanded in recent years, clinical diagnosis is possible only when metastases are present, requiring chronic complicated medical management. A positive development is that the recent evolution of molecularly-targeted therapy in oncology promotes the evolution of innovative tools for the management of these tumors. A diverse assortment of medical specialists is needed to improve outcomes and orchestrate the therapeutic care plan for NET patients.

Reciprocal changes of serum adispin and visfatin levels in patients with type 2 diabetes after an overnight fast.

OBJECTIVE: In order to elucidate the interrelationship of adipokines in glucose hemiostasis, we determined the concentration of visfatin and adipsin in blood samples in patients with type 2 diabetes and age-matched controls after an overnight fast. SUBJECTS AND METHODS: We enrolled 37 patients with known type 2 diabetes -21 males and 16 females, aged 62.95 ± 15.72 years and 43 controls- 28 males and 15 females, aged 60.79 ± 12.67 years. Blood samples were collected after an overnight fast and routine biochemical parameters such as glucose, cholesterol, HDL, LDL, triglycerides along with Hb1Ac, insulin and c-peptide, in addition to circulating visfatin and adipsin were determined in all samples. Data were considered significant at a level of p < 0.05. RESULTS: In patients with type 2 diabetes, circulating adipsin levels were decreased and inversely related with glucose levels while circulating visfatin was increased significantly in the fasting state. CONCLUSION: These results implicate the adipokines adipsin and visfatin as possible participants in the pathogenesis of type 2 diabetes.

Thyroid function and prevalence of anti-thyroperoxidase (TPO) and anti-thyroglobulin (Tg) antibodies in outpatients hospital setting in an area with sufficient iodine intake: influences of age and sex.

In order to examine the prevalence of thyroid disease in a hospital outpatient setting, in an area of sufficient iodine intake, serum levels of TSH, T4, T3, anti-Tg and anti-TPO antibodies were examined in 909 individuals with an age range of 12.4 to 88.5 years, participating in a checkup outpatient setting. The study was conducted in Henry Dynant Hospital located in the metropolitan area of Athens, Greece, during a 2 year period. Hormonal parameters were determined by chemiluminescence immunoassay. Overt thyrotoxicosis was found in 4.95% of the total population and subclinical thyrotoxicosis in 5.5%. Overt hypothyroidism was found in 1.43% and subclinical hypothyroidism in 4.51%. In male population, overt thyrotoxicosis was found in 4.4 % and subclinical thyrotoxicosis was also found in 4.4%. On the other hand, overt hypothyroidism was found in 1.4% and subclinical hypothyroidism was found in 3.7% in males. In female population, overt thyrotoxicosis was found in 5.2% whereas subclinical thyrotoxicosis was found in 6.0%. Overt hypothyroidism was found in 1.5% and subclinical hypothyroidism was found in 4,9% in females. Positive anti-TPO antibodies were detected more often (30.4%) than anti-Tg (15.4%) in the tested population. The positivity in both anti-TPO and anti-Tg antibodies was correlated with abnormally high TSH concentrations after the age of 50 years, especially in female population. In conclusion distinct profile of thyroid hormonal parameters was observed in inhabitants in the metropolitan area of Athens, with overt thyrotoxicosis strikingly overcome overt hypothyroidism while subclinical forms of each dysfunction also exhibit analogous results.

Osteoporosis in patients with breast and prostate cancer: effect of disease and treatment modalities.

The skeleton is constantly being remodelled through the simultaneous resorption of bone and formation of new bone. Significant effects on bone metabolism are produced due to cancer treatment especially of breast and prostate origin, even in the absence of bone metastases. These pathological changes are known as cancer treatment-induced bone loss. Bone mass loss and osteoporosis may cause an increased risk of fractures due to a reduction in bone volume and microarchitectural deterioration. On the other hand, the skeleton is both the most common organ affected by metastatic cancer and the site that produces the greatest morbidity for patients. Recent advances in our understanding of bone biology and the pathways by which cancer metastasizes and spreads to bone have contributed to the development of several important new drugs targeting these processes. This article summarizes our current knowledge and recommendations to advanced biology of metastasis, focusing on breast and prostate cancer.

Recent advances in molecular diagnosis of thyroid cancer.

Recent molecular studies have described a number of abnormalities associated with the progression and dedifferentiation of thyroid carcinoma. These distinct molecular events are often associated with specific stages of tumor development. In particular, remarkable advances have occurred in several major biological areas of thyroid cancer, including the molecular alterations for the loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations, and the aberrant methylation of functionally important genes in thyroid tumorigenesis and pathogenesis. Recognition of these features is crucial to the management of patients with thyroid cancer. Novel treatments are being designed based on our enhanced understanding of this disease process.

Hypoxemic resuscitation from hemorrhagic shock prevents lung injury and attenuates oxidative response and IL-8 overexpression.

We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents lung injury and explored the mechanisms involved. We subjected rabbits to hemorrhagic shock for 60 min by exsanguination to a mean arterial pressure of 40 mm Hg. By modifying the fraction of the inspired oxygen, we performed resuscitation under normoxemia (group NormoxRes, P(a)O(2)=95-105 mm Hg) or hypoxemia (group HypoxRes, P(a)O(2)=35-40 mm Hg). Animals not subjected to shock constituted the sham group (P(a)O(2)=95-105 mm Hg). We performed bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, and morphological studies. U937 monocyte-like cells were incubated with BAL fluid from each group. Cell peroxides, malondialdehyde, proteins, and cytokines in the BAL fluid were lower in sham than in shocked animals and in HypoxRes than in NormoxRes animals. The inverse was true for ascorbic acid and reduced glutathione. Lung edema, lung neutrophil infiltration, myeloperoxidase, and interleukin (IL)-8 gene expression were reduced in lungs of HypoxRes compared with NormoxRes animals. A colocalized higher expression of IL-8 and nitrotyrosine was found in lungs of NormoxRes animals compared to HypoxRes animals. The BAL fluid of NormoxRes animals compared with HypoxRes animals exerted a greater stimulation of U937 monocyte-like cells for proinflammatory cytokine release, particularly for IL-8. In the presence of p38-MAPK and Syk inhibitors and monosodium urate crystals, IL-8 release was reduced. We conclude that hypoxemic resuscitation from hemorrhagic shock ameliorates lung injury and reduces oxygen radical generation and lung IL-8 expression.

Obesity modulation - the role in carcinogenesis.

Obesity has been recognized as an important risk factor for many serious medical conditions. The association of obesity with an increased risk of many cancers is of enormous economic importance to the health industry.The metabolic syndrome and visceral obesity have an increasing prevelance and incidence in the general population.The actual prevelance of the metabolic syndrome is 24% in US population and between 24,6% and 30.9% in Europe. Recent evidence from epidemiologic and basic research studies, as well as clinical and intervention studies, supports the emerging hypothesis that metabolic syndrome may be an important etiologic factor for the onset of cancer. In addition, increased body weight has recently been shown to be associated with an increased risk of cancers at multiple specific sites. The close interaction between cancer cells and adipocytes is an intriguing issue in tumor biology. In nowdays, several metabolic markers are implicated in the development and progression of several malignancies. This review describes the emerging data concerning the role of metabolic markes in tumor cell growth and relates them to their future clinical prospects.

Decreased plasma ghrelin levels in patients with advanced cancer and weight loss in comparison to healthy individuals.

BACKGROUND: Ghrelin is a growth hormone-releasing acylated peptide found to be an appetite stimulant and low levels of it are detected in cachexia. The aim of the present study was to investigate the plasma ghrelin levels in cancer patients with a low performance status and weight loss and compare them with those of healthy individuals without weight loss. PATIENTS AND METHODS: Thirty patients (median age 65 years) with different malignancies, mainly pancreatic and gastric, and 27 healthy individuals (median age 62 years) were examined. The gender of both groups was well balanced. Plasma ghrelin was measured by a radioimmunoassay kit that uses a polyclonal antibody which recognizes the C-terminal of ghrelin. RESULTS: There was a statistically significant difference in the plasma ghrelin levels of the patients vs. the controls, with the patients having much lower levels (p<0.001). CONCLUSION: The notable reduction of ghrelin levels might be due to the severity and progression of the disease.

Positive correlation of PTH-related peptide with glucose in type 2 diabetes.

Type 2 diabetes is characterized by hyperglycemia resulting from insulin resistance in the setting of inadequate beta-cell compensation. Recent studies indicate that for attaining a well-functioning ss-cell mass, parathyroid hormone-related protein (PTHrP) is a very promising candidate among several insulinotropic peptides. In order to elucidate its role, we determine the levels of PTHrP, insulin and c-peptide in type 2 diabetics and in normal subjects in the fasting state. We enrolled 28 patients (16 men and 12 postmenopausal women) with type 2 diabetes and twenty eight aged-matched healthy individuals as control subjects (15 men and 13 women). PTHrP was statistically significant correlated with glucose in type 2 diabetes and in normal subjects in the fasting state. Additionally, PTHrP serum levels exhibited a significant increase in type 2 diabetes compared to control subjects. Interestingly, PTHrP showed a positive correlation with insulin levels only among healthy individuals presumably due to defective glucose stimulated insulin secretion known to occur in type 2 diabetics. In conclusion, the strong positive relation of PTHrP with glucose in the fasting state in patients with type 2 diabetes mellitus raises several questions for further experimentation concerning its exact role and physiological significance.

The role of parathyroid hormone-related protein (PTHrP) in the pathophysiology of diabetes mellitus.

Type 2 diabetes is characterized by hyperglycemia resulting from insulin resistance in the setting of inadequate beta-cell compensation. Impaired beta-cell function and possibly beta-cell mass appear to be reversible, particularly at early stages of the disease. Pancreatic beta-cells possess the potential to greatly expand their function and mass in both physiologic and pathologic states by several mechanisms, including hypertrophy and proliferation of existing beta-cells, increased insulin production and secretion, and formation of new beta-cells from progenitor cells. Recently a large number of factors controlling the differentiation of beta-cells has been identified and among them the parathyroid hormone-related protein (PTHrP) emerged as a strong candidate in beta-cell survival. In this review, we will highlight our current knowledge in PTHrP physiology implicating its role into the mechanisms of beta-cell mass regulation and consequently in diabetes. Further research into mechanisms will reveal the key modulators of beta-cell failure and thus identify possible novel therapeutic targets.

Active contours guided by echogenicity and texture for delineation of thyroid nodules in ultrasound images.

Thyroid nodules are solid or cystic lumps formed in the thyroid gland and may be caused by a variety of thyroid disorders. This paper presents a novel active contour model for precise delineation of thyroid nodules of various shapes according to their echogenicity and texture, as displayed in ultrasound (US) images. The proposed model, named joint echogenicity-texture (JET), is based on a modified Mumford-Shah functional that, in addition to regional image intensity, incorporates statistical texture information encoded by feature distributions. The distributions are aggregated within the functional through new log-likelihood goodness-of-fit terms. The JET model requires only a rough region of interest within the thyroid gland as input and automatically proceeds with precise delineation of the nodules, revealing their shape and size. The performance of the JET model was validated on a range of US images displaying hypoechoic and isoechoic nodules of various shapes. The quantification of the results shows that the JET model: 1) provides precise delineations of thyroid nodules as compared to "ground truth" delineations obtained by experts and 2) copes with the limitations of the previous thyroid US delineation approaches as it is capable of delineating thyroid nodules regardless of their echogenicity or shape.

Increased alpha-subunit response coexist with increased TSH response to TRH test in healthy individuals.

OBJECTIVE: The alpha-subunit (Alpha-SU) response to TRH was studied to examine the response of alpha-SU under TRH stimulation in normal situation. METHODS: Thirty seven healthy individuals were included in the study. They were divided into two groups according to the data taken: A with TSH equal or more than seven fold the basal values (0: 3.14+/-1.2 microU/ml., 30 after TRH: 20.22+/-4.6 microU/ml) and B with TSH 2 to 6 fold the basal values (0: 0.5+/-0.1 microU/ml., 30 after TRH: 2.9+/-0.5 microU/ml). Both groups exhibited similar FT3 and FT4 levels. RESULTS: In group A, prolactin displayed a 3 fold increase from the basal values, whereas alpha-SU increased 4 fold with a difference being statistically significant (p<0.001). In contrast, in group B individuals neither prolactin nor alpha-SU exhibited any significant difference from the basal values. CONCLUSION: The expression of alpha-SU upon TRH stimulation is dependent on the TSH basal values.

Thyroid abscess due to a mixed anaerobic infection with Fusobacterium mortiferum.

A rare case of a thyroid abscess due to mixed anaerobic flora containing Fusobacterium mortiferum in an immunocompetent patient is described. The patient was successfully treated with immediate surgical intervention and appropriate antimicrobial agents.

The role of galanin in metabolic disorders leading to type 2 diabetes mellitus.

A large number of neurotransmitters have been identified that influence food intake when administered directly into the central nervous system of experimental animals. In some cases, there is evidence that endogenous release is stimulated by the presence of food in the gastrointestinal tract and that blockage of the signal results in an increase in meal size, indicating that these signals are likely to represent true satiety signals. Galanin, a 29-amino acid peptide originally isolated from porcine intestine, is widely distributed in the central and peripheral nervous systems and the endocrine system. While the precise physiological role of galanin in the daily pattern of feeding behavior still remains to be fully elucidated, there may be a correlation between galanin and metabolic disorders leading to type 2 diabetes mellitus.