Iodide is an essential micronutrient present in very small quantities in the human body, with a fundamental action for the adequate synthesis of thyroid hormones, which are critical for cell differentiation, growth and metabolism. In the form of iodide, iodine is widely distributed in the environment, although in an irregular manner, occurring in abundant amounts in the oceans and in coastal areas and scarcely found on islands and mountains. The diet is the main source of iodine, whose intake varies according to the amount present in soil and water and according to eating habits. Governmental policies have been adopted to satisfy and guarantee the necessary daily supply of iodine, such as fortification of industrialized salt for domestic iodine consumption or addition to the bread commonly consumed in a given region, or the offer of iodized oil to the population, or even iodine supplementation through medications. Iodide deficiency is the main avoidable cause of brain damage to fetuses and children, as well as retardation of psychomotor development. Thyroid hormones are almost universally involved in the development and proliferation of fetal neural tissue. Permanent lesions of the cerebral cortex, hippocampus and cerebellum may occur, with loss of, or damage to the brainstem or spinal cord, affecting cortical areas that integrate highly specialized stimuli, which become poorly defined on an anatomical basis, including silent areas of the associative cortex. One of the more significant metabolic problems due to dietary iodine deficiency is the presence of goiter (increased volume of the thyroid gland). Thyroid carcinoma is the most frequent endocrine neoplasia affecting the human species and plasma iodine concentration is related to the development of specific subtypes of this neoplasia. An increased prevalence of follicular carcinoma, a more aggressive tumor, has been observed in areas of iodine deficiency, while the correction of this deficiency is associated with a higher prevalence of papilliferous carcinoma, a less aggressive form. CONCLUSION: An ideal plasma iodide concentration is necessary to insure the proper mental development of fetuses and young children and to minimize the aggressiveness of thyroid cancer from follicular cells in humans.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

The literature on the causation of multiple sclerosis (MS), both genetic and environmental, extends over hundreds of years, with no firm conclusions on the exact role of autoimmunity and lifestyle. The epidemiology of MS was the basis for this review, but with a new, extensive examination of genes pertaining to each disorder, and disease of first, and second, degree relatives of those with MS. The author’s motivation was to discover some relationship between MS, and notable familial conditions, as the heredity of MS is concluded to be 30%, and the disorders had a chronic and/or idiopathic nature. This investigation hoped to further understand the randomness of MS- who acquires it, and what symptoms develop- after the author’s decades of observing several incidences of multiple members developing MS in a single family. Online databases for the human genome were used to link genes to MS, and symptoms, including excessive depression, fatigue and suicide rates, in coordination with linking genes for specific familial conditions including seizures, stroke, mental illness, bowel disorders, and thyroid conditions. Interesting associations were found, notably a cluster of Th2 cytokines, known to cure the animal model of MS, important receptors for neurotransmitters and hormones, a gene specific to Epstein Barr Virus, and potential genes for mitochondrial dysfunction. The results surprised the author, showing polygenic regions of chromosome 2 and 5, especially a cluster at loci 5q31-q33, may be dysregulated. The conclusion agrees with past hypotheses MS results not from a single gene, but from various genes, including those expressed in glial cells. The individual theories to the causation of MS, starting with Charcot may be explained by multiple pathways converging into a single disease outcome. In coordination with a sunlight factor, chromosome 2 appears to mediate the immune system, and inflammation, through ultraviolet radiation producing vitamin D3 in the skin, but additionally through peptides formed in the melanocyte stimulating and concentrating hormone class. The impact of stress in MS could be primary, given the loci of several stress-related and stress-modulated genes on these chromosomes, and calls for more appreciation of, and greater care for, the MS patients’ state of mind.

The dynamic and never exactly repeatable tumor transcriptomic profile of people affected by the same form of cancer requires a personalized and time-sensitive approach of the gene therapy. The Gene Master Regulators (GMRs) were defined as genes whose highly controlled expression by the homeostatic mechanisms commands the cell phenotype by modulating major functional pathways through expression correlation with their genes. The Gene Commanding Height (GCH), a measure that combines the expression control and expression correlation with all other genes, is used to establish the gene hierarchy in each cell phenotype. We developed the experimental protocol, the mathematical algorithm and the computer software to identify the GMRs from transcriptomic data in surgically removed tumors, biopsies or blood from cancer patients. The GMR approach is illustrated with applications to our microarray data on human kidney, thyroid and prostate cancer samples, and on thyroid, prostate and blood cancer cell lines. We proved experimentally that each patient has his/her own GMRs, that cancer nuclei and surrounding normal tissue are governed by different GMRs, and that manipulating the expression has larger consequences for genes with higher GCH. Therefore, we launch the hypothesis that silencing the GMR may selectively kill the cancer cells from a tissue.

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep-wake cycle, locomotion and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep-wake cycle of rats increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin-A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin-A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons which may be responsible for alterations of the sleep-wake cycle.

Thyroid nodules (TNs) are common thyroid lesions in older population. Few studies focused on the prevalence of TNs and its relationship to lifestyle characteristics and dietary habits in centenarians. The current study aimed to determine the prevalence of TNs in Chinese centenarians using high-resolution ultrasound equipment and investigate its relationship to lifestyles and dietary habits. The current study was part of China Hainan Centenarian Cohort Study (CHCCS) which conducted in Hainan, an iodine sufficient region in China. A total of 874 permanent residents aged 100 years or older (mean age, 102.8 ± 2.8 years) without any missing data were included in the analysis. Among the participants, 649 of them were detected at least one thyroid nodule under the ultrasound examinations. The overall prevalence rate of TNs was 74.3%. The prevalence of TNs was higher in participants who were females, hypertension, diabetes, and underweight than their counterparts. Multivariate logistic regression analyses showed that being female, hypertension, diabetes, betel quid consumption, red meat consumption were independent risk factors, while being underweight, and nut consumption were independent protective factors for TNs. Our findings indicate that the presence of thyroid nodules was highly prevalent in Chinese centenarians, particularly in females. In addition to gender, hypertension, diabetes, and underweight, the presence of TNs was independently associated with betel quid, red meat, and nut consumptions. Further prospective studies are warranted to verify these associations in population from different age strata, races, cultures, and iodine backgrounds.

Endocrine disruptor compounds are exogenous agents able to interfere with a gland function, exerting their action across different functional passages, from the synthesis to the metabolism and binding to receptors of the hormone produced. Several issues such as different levels and time of exposure and different action across different ages as well as gender, make the study of endocrine disruptors still a challenge. Thyroid is very sensitive to the action of disruptors, and considering the importance of a correct thyroid function for physical and cognitive functioning, addressing this topic should be considered a priority. In this review we examined the most recent studies, many of them concentrating on maternal and child exposure, conducted to assess the impact of industrial chemicals which showed an impact on thyroid function. So far, the number of studies conducted on that topic is not sufficient to provide solid conclusions and lead to homogeneous guidelines. The lack of uniformity is certainly due to differences in areas and populations examined, the different conditions of exposures and the remarkable inter-subject variability. Nonetheless, the European Commission for Health and Food Safety is implementing recommendations to ensure that substances identified as endocrine disruptors will be withdrawn from the market.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.