Endocrine and Metabolic Disorders

Correction to: Statins, metformin, proprotein-convertase-subtilisin-kexin type-9 (PCSK9) inhibitors and sex hormones: Immunomodulatory properties? The authors would like to note that several errors had occurred, especially in Table 2, Tables 5, 6 and 7, Figure 13, and in the legend of Figure 23.

Nutritional and non-nutritional agents that stimulate white adipose tissue browning Abstract Obesity is a public health problem present in both developed and developing countries. The white adipose tissue (WAT) is the main deposit of lipids when there is an excess of energy. Its pathological growth is directly linked to the development of obesity and to a wide number of comorbidities, such as insulin-resistance, cardiovascular disease, among others. In this scenario, it becomes imperative to develop new approaches to the treatment and prevention of obesity and its comorbidities. It has been documented that the browning of WAT could be a suitable strategy to tackle the obesity epidemic that is developing worldwide. Currently there is an intense search for bioactive compounds with anti-obesity properties, which present the particular ability to generate thermogenesis in the brown adipose tissue (BAT) or beige. The present study provide recent information of the bioactive nutritional compounds capable of inducing thermogenesis and therefore capable of generate positive effects on health.

Prader- Willi syndrome: An uptodate on endocrine and metabolic complications Abstract Prader-Willi syndrome (PWS) is a genetic disorder characterized by short stature, low lean body mass, muscular hypotonia, mental retardation, behavioral abnormalities, dysmorphic features, and excessive appetite with progressive obesity. It is caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13. This genetic disorder has an estimated prevalence that ranges between 1/10,000–1/30,000. Hypothalamic dysfunction is a common finding in PWS and it has been implicated in several manifestations of this syndrome such as hyperphagia, temperature instability, high pain threshold, sleep disordered breathing, and multiple endocrine abnormalities. These include growth hormone deficiency, central adrenal insufficiency, hypogonadism, hypothyroidism, and obesity often complicated by type 2 diabetes. The aim of this manuscript is to overview the current literature on metabolic and endocrine complications of PWS, focusing on human studies and providing insights on the physio pathological mechanisms. A careful management of metabolic and endocrine complications can contribute to improve quality of life, prevent complications, and prolong life expectancy of PW patients.

Primary tumors of the posterior pituitary: A systematic review Abstract In 2017, the World Health Organization established that pituicytoma, granular cell tumor (GCT), spindle cell oncocytoma (SCO) and sellar ependymomas (SE) are posterior pituitary tumors (PPT). They probably arise from the pituicytes and may constitute a unique histopathological entity. We carried out a systematic review using PubMed's database. A total of 266 patients with pathological diagnosis of PPT (135 pituicytomas, 69 GCT, 47 SCO, 8 SE and 7 mixed histology tumors) were analyzed. Gender distribution was identical and median age at diagnosis was 48 ± 21.8 years. Main presentation symptoms were visual disorders (n = 142; 58.1%), headache (n = 99; 40.5%), hypopituitarism (n = 84; 34.4%), hypercortisolism (n = 10; 4.1%), polyuriapolydipsia (n = 6; 2.4%) and acromegaly features (n = 5; 2.0%). On MRI, 122 (47.6%) patients showed sellar with suprasellar extension masses, 67 (23.1%) were suprasellar and 63 (24.6%) exclusively sellar. Median tumor size was 22.0 ± 14.2 mm. Two hundred sixty four patients underwent surgery, transphenoidal access was selected in 132 (64.4%) and craniotomy in 58 (28.3%). Complications were hypopituitarism (n = 70; 42.1%), diabetes insipidus (n = 55; 33.1%) and hemorrhage (n = 50; 30.1%). Tumor persisted in 93 patients (45.6%) and recurred in 13 (6.4%). Regarding comparison between main types of PPT, SCO patients were diagnosed later (60.0 vs 47.0 vs 47.0 years, p = 0.023), the tumor was larger 25.0 mm [10.8] vs 20.0 mm [14.2] vs 2.0 mm [15.0] and they were frequently sellar with suprasellar extension tumors (71.7% vs 46.2% vs 32.8%, p = 0.003) compared to pituicytoma and GCT. In conclusion, PPT are rare tumors and have been misdiagnosed mainly as non-functioning pituitary adenomas. Different types of PPT share similar epidemiology, clinical manifestations and surgical outcomes. Surgery is the only curative option but complications and subtotal resection are common.

Functions of stem cells of thyroid glands in health and disease Abstract Thyroid gland has been implicated in the regulation of many functions using endocrine, paracrine and autocrine signals. Functional thyroid follicular cells derived from stem cells attracted a great interest from researchers as a strategy for thyroid's regenerative therapy. Thyroid has a very low rate of turnover; however, studies showed that the regenerative ability is enhanced following diseases or thyroidectomy, which promotes the role of stem cell. The objective of this review is to summarize the morphological characterization and the expression of stem cell genes/markers in the thyroid. Also, to highlight the mechanisms of tumor formation in thyroid via its stem cells. The most important thyroid stem cell's markers are: stem cell antigen 1 (SCA-1), octamer-binding transcription 4 (OCT-4), p63, CD34+ CD45-, paired box gene 8 (PAX-8), thyroid transcription factor 1 (TTF-1), thyroid transcription factor 2 (TTF-2), hematopoietically expressed homeobox protein HHEX, the transcription factor GATA-4, hepatocyte nuclear factor 4-α (HNF-4-α) and homeobox transcription factor Nanog (hNanog). This review highlights the functional characterization describing the mechanisms of stem cell's differentiation into functional thyroid follicle and proposing mechanisms involving in cancer formation through one of these cell types: fetal cell, thyroblasts, prothyrocytes, certain genetic mutation in the mature thyroid cells or presence of a special type of cells (cancer stem cell) which are responsible for different types of cancer formation. Understanding the mechanisms of thyroid's stem cell in cancer formation and the expression of the biomarkers in normal and abnormal thyroid status are promising physiological tools in promoting thyroid regeneration and in provision management for thyroid cancer.

Prolactin and human weight disturbances: A puzzling and neglected association Abstract Weight gain at the outset of prolactinomas in many women is well documented. Yet, this symptom is absent from the clinical descriptions of the disease in textbooks and reviews. This omission is almost certainly due to the absence of a physiological explanation for the phenomenon, as prolactin is not a recognized fat promoting hormone. In this review we present the clinical evidence for a relationship between prolactin and fat accumulation and address some possible mechanisms involved. We put forward the hypothesis that prolactin is a component of a neuroendocrine program – maternal subroutine – aimed at optimizing the care of the young through the production of milk, promotion of maternal behavior and increase in the metabolic efficiency of the mother. These adaptations can enable her to face the extraordinary metabolic expenses of pregnancy and nursing, especially during times of suboptimal environmental conditions. We emphasize the uniqueness of prolactin in that it is a hormone that is tonically inhibited and which has its major effects on the regulation of an inter-individual (the mother – offspring dyad), rather than an intra-individual, system. This approach opens a window to consider the possibility of external events as regulators of this system. It also allows addressing a variety of hitherto unexplained findings reported in the literature. Examples include: association of prolactinomas with paternal deprivation and with stressful life events; pseudocyesis; acute life event-driven episodes of galactorrhea; episodes of rapid weight gain following a life event; prolactin surges (without associated cortisol surges) following some psychological stresses.

Effect of resveratrol on metabolic syndrome components: A systematic review and meta-analysis Abstract We summarized 16 controlled studies and evaluated the correlation of resveratrol supplementation with metabolic parameters such as the body weight, waist circumference (WC), systolic blood pressure (sbp), HDL, total cholesterol, triglyceride and glucose levels. This meta-analysis was carried out to determine the association between the resveratrol intake with metabolic parameters in metabolic syndrome patients. PubMed, Scopus, Cochrane and Google Scholar were searched from inception to December 2018 using relevant keywords. All articles were independently reviewed by two authors using predetermined selection criteria. We have selected the studies that investigated the effects of resveratrol on metabolic parameters. Of 16 studies, 10 were performed on human subjects, and in 6 studies animal models were used. Standard mean difference (SMD) with 95% confidence interval were determined using Der Simonian and Laird random-effects modeling, when there was a significant heterogeneity between studies. Funnel plot and Egger's test were conducted to examine the risk of publication bias. Pooled effect sizes in human studies indicated a significant impact of resveratrol supplementation on glucose level [−1.73 (−2.99, −0.47); p = 0.007)] and WC [−1.73 (−2.79, −0.67); p = 0.001] compared with the control group. Also combining the results of studies on rat samples (n = 6), indicated significant effect of resveratrol on decreasing weight [−22.95 (−44.74, −1.17); p = 0.04], TGs [−6.76 (−11.10, −2.42); p = 0.001], sbp [−7.30 (−12.48, −2.13); p = 0.006], and it can influence significantly on increasing HDL level (4.75 (1.87, 7.63); p = 0.001). However, resveratrol was not significantly effective on total cholesterol in both samples. The results of subgroup analysis of human studies showed that resveratrol has significant effect on metabolic parameters (glucose level and WC) at the dosage of > 500 mg and with long-term interventions ≥ 10 weeks. Administration of resveratrol can meaningfully reduce the BW, WC, TGs, and glucose level, also it can increase HDL, but not total cholesterol.

Structure and function of the exocrine pancreas in patients with type 1 diabetes Abstract In the last 10 years, several studies have shown that the pancreas of patients with type 1 diabetes (T1D), and even of subjects at risk for T1D, was smaller than the pancreas from healthy subjects. This arose the question of the relationships between the endocrine and exocrine parts of the pancreas in T1D pathogenesis. Our review underlines that histological anomalies of the exocrine pancreas are common in patients with T1D: intralobular and interacinar fibrosis, acinar atrophy, fatty infiltration, leucocytic infiltration, and pancreatic arteriosclerosis are all frequent observations. Moreover, 25% to 75% of adult patients with T1D present with pancreatic exocrine dysfunction. Our review summarizes the putative causal factors for these structural and functional anomalies, including: 1/ alterations of insulin, glucagon, somatostatin and pancreatic polypeptide secretion, 2/ global pancreatic inflammation 3/ autoimmunity targeting the exocrine pancreas, 4/ vascular and neural abnormalities, and 5/ the putative involvement of pancreatic stellate cells. These observations have also given rise to new theories on T1D: the primary event of T1D pathogenesis could be non-specific, e.g bacterial or viral or chemical, resulting in global pancreatic inflammation, which in turn could cause beta-cell predominant destruction by the immune system. Finally, this review emphasizes that it is advisable to evaluate pancreatic exocrine function in patients with T1D presenting with gastro-intestinal complaints, as a clinical trial has shown that pancreatic enzymes replacement therapy can reduce the frequency of hypoglycemia and thus might improve quality of life in subjects with T1D and exocrine failure.

Role of growth factors and cytokines in diabetic foot ulcer healing: A detailed review Abstract The aim of the review is to examine the role of growth factors and cytokines in the management of Diabetic Foot Ulcers, such as platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and Insulin like growth factor (IGF). Taking this a step further, the role of Hypoxia-inducible factors (HIFs), Transforming growth factor beta 1 (TGF-β-1) and other growth factors have also been examined, with regard to the treatment of diabetic foot ulcers. The roles of these above-mentioned growth cytokines have been analyzed by studying various scholastic articles. The complete process of wound healing is implemented and regulated by numerous cytokines and human growth factors. The findings of the study indicate that wound healing of diabetic foot ulcers is a complex and extremely challenging biological and molecular process that involves coordinated efforts of multiple cell types. The therapeutic effects of various growth factors in the clinical management of wounds are chronic venous ulcers, pressure ulcers, and diabetic foot ulcers. It has been concluded that altercations of various cytokines are found in patients enduring diabetic foot ulcers. In a similar way, changes in the level of cytokines are also found in patients suffering from other diabetic complications such as diabetic nephropathy, retinopathy, and neuropathy. Subsequently, the diabetic wound healing process can be accelerated by regulating the levels of the cytokines.

Can blood glucose value really be referred to as a metabolic parameter? Abstract In clinical guidelines, near-normoglycaemia is recommended as the basic therapeutic target in diabetes mellitus. This proposal suggests that euglycaemia is associated with eumetabolism and that hyperglycaemia is an indicator of dysmetabolism. The authors analysed the relationship between short/long-term blood glucose values and cellular metabolism in various pathophysiological settings. The following types of dysmetabolism are suggested: "hyperglycaemic dysmetabolism based on insulin deficiency", "hyperglycaemic dysmetabolism based on glucose toxicity", "euglycaemic dysmetabolism", "dysmetabolism of ischaemic/reperfusional origin", and "chronic stress-mediated dysmetabolism". The relationship between dysmetabolic states of various origin was also analysed. The authors conclude that the blood glucose value can only be accepted as a general metabolic parameter with marked limitations. The main arguments of this statement are that euglycaemia is not necessarily associated with eumetabolism and that acute hyperglycaemia does not necessarily indicate dysmetabolism. Identical cell metabolic performance can be supported by different biochemical energy-producing mechanisms associated with identical blood glucose values. Both positive and negative metabolic balance of cell metabolism can occur at identical blood glucose values. A further finding is that chronic hyperglycaemia acts simultaneously as a marker and as a maker of dysmetabolism; therefore, the achievement of near normoglycaemia remains the basic therapeutic goal in diabetes treatment. Insulin administration can beneficially influence dysmetabolic states of various origins. In the evolution of and interrelationships among various dysmetabolic states, the central role of chronic stress is emphasized. Discrepancies between blood glucose values and cellular metabolism are substantiated by the transporter nature of the blood glucose value; this value reflects the result of bidirectional glucose movement into and out of the tissues.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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alsfakia@gmail.com