Vitamin D, a crucial hormone in the homeostasis and metabolism of calcium bone, has lately been found to produce effects on other physiological and pathological processes genomically and non-genomically, including the cardiovascular system. While lower baseline vitamin D levels have been correlated with atherogenic blood lipid profiles, 25(OH)D supplementation influences the levels of serum lipids in that it lowers the levels of total cholesterol, triglycerides, and LDL-cholesterol and increases the levels of HDL-cholesterol, all of which are known risk factors for cardiovascular disease. Vitamin D is also involved in the development of atherosclerosis at the site of the blood vessels. Deficiency of this vitamin has been found to increase adhesion molecules or endothelial activation and, at the same time, supplementation is linked to the lowering presence of adhesion surrogates. Vitamin D can also influence the vascular tone by increasing endothelial nitric oxide production, as seen in supplementation studies. Deficiency can lead, at the same time, to oxidative stress and an increase in inflammation as well as the expression of particular immune cells that play a pivotal role in the development of atherosclerosis in the intima of the blood vessels, i.e., monocytes and macrophages. Vitamin D is also involved in atherogenesis through inhibition of vascular smooth muscle cell proliferation. Furthermore, vitamin D deficiency is consistently associated with cardiovascular events, such as myocardial infarction, STEMI, NSTEMI, unstable angina, ischemic stroke, cardiovascular death, and increased mortality after acute stroke. Conversely, vitamin D supplementation does not seem to produce beneficial effects in cohorts with intermediate baseline vitamin D levels.

Background: Metabolomics—the novel science that evaluates the multitude of low-molecular-weight metabolites in a biological system, provides new data on pathogenic mechanisms of diseases, including endocrine tumors. Although development of metabolomic profiling in pituitary disorders is at an early stage, it seems to be a promising approach in the near future in identifying specific disease biomarkers and understanding cellular signaling networks. Objectives: To review the metabolomic profile and the contributions of metabolomics in pituitary adenomas (PA). Methods: A systematic review was conducted via PubMed, Web of Science Core Collection and Scopus databases, summarizing studies that have described metabolomic aspects of PA. Results: Liquid chromatography tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) spectrometry, which are traditional techniques employed in metabolomics, suggest amino acids metabolism appears to be primarily altered in PA. N-acetyl aspartate, choline-containing compounds and creatine appear as highly effective in differentiating PA from healthy tissue. Deoxycholic and 4-pyridoxic acids, 3-methyladipate, short chain fatty acids and glucose-6-phosphate unveil metabolite biomarkers in patients with Cushing's disease. Phosphoethanolamine, N-acetyl aspartate and myo-inositol are down regulated in prolactinoma, whereas aspartate, glutamate and glutamine are up regulated. Phosphoethanolamine, taurine, alanine, choline-containing compounds, homocysteine, and methionine were up regulated in unclassified PA across studies. Intraoperative use of ultra high mass resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which allows localization and delineation between functional PA and healthy pituitary tissue, may contribute to achievement of complete tumor resection in addition to preservation of pituitary cell lines and vasopressin secretory cells, thus avoiding postoperative diabetes insipidus. Conclusion: Implementation of ultra high performance metabolomics analysis techniques in the study of PA will significantly improve diagnosis and, potentially, the therapeutic approach, by identifying highly specific disease biomarkers in addition to novel molecular pathogenic mechanisms. Ultra high mass resolution MALDI-MSI emerges as a helpful clinical tool in the neurosurgical treatment of pituitary tumors. Therefore, metabolomics appears to be a science with a promising prospect in the sphere of PA, and a starting point in pituitary care.

The therapeutic response heterogeneity in acromegaly persists, despite the medical–surgical advances of recent years. Thus, personalized medicine implementation, which focuses on each patient, is justified. Metabolomics would decipher the molecular mechanisms underlying the therapeutic response heterogeneity. Identification of altered metabolic pathways would open new horizons in the therapeutic management of acromegaly. This research aimed to evaluate the metabolomic profile in acromegaly and metabolomics’ contributions to understanding disease pathogenesis. A systematic review was carried out by querying four electronic databases and evaluating patients with acromegaly through metabolomic techniques. In all, 21 studies containing 362 patients were eligible. Choline, the ubiquitous metabolite identified in growth hormone (GH)-secreting pituitary adenomas (Pas) by in vivo magnetic resonance spectroscopy (MRS), negatively correlated with somatostatin receptors type 2 expression and positively correlated with magnetic resonance imaging T2 signal and Ki-67 index. Moreover, elevated choline and choline/creatine ratio differentiated between sparsely and densely granulated GH-secreting PAs. MRS detected low hepatic lipid content in active acromegaly, which increased after disease control. The panel of metabolites of acromegaly deciphered by mass spectrometry (MS)-based techniques mainly included amino acids (especially branched-chain amino acids and taurine), glyceric acid, and lipids. The most altered pathways in acromegaly were the metabolism of glucose (particularly the downregulation of the pentose phosphate pathway), linoleic acid, sphingolipids, glycerophospholipids, arginine/proline, and taurine/hypotaurine. Matrix-assisted laser desorption/ionization coupled with MS imaging confirmed the functional nature of GH-secreting PAs and accurately discriminated PAs from healthy pituitary tissue.

Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

Introduction: Primary hyperparathyroidism (PHPT) is a multisystemic endocrine disorder characterized by an incompletely understood pathogenesis, a complex clinical picture and various complications. Chronic inflammation represents a state that can affect the normal function of cells and cause tissue damage, therefore increasing the risk of certain diseases, including cancer, metabolic, cardiovascular or neurodegenerative disorders.Aim: Reviewing existing data on markers of inflammation in patients with PHPT, with potential implications in understanding the pathogenesis of PHPT, stratifying the risk for complications and providing new diagnostic biomarkers and a personalized therapeutic approach, especially in patients who cannot be operated on.Methods: A systematic review was conducted by searching in four electronic databases (PubMed, Embase, Web of Science and Scopus) and summarizing data from studies that evaluated inflammatory markers in patients with PHPT.Results: The review included a total of 28 articles, encompassing data from 1572 patients diagnosed with PHPT. Various markers associated with chronic inflammation, including High sensitivity C-Reactive Protein (CRP), Tumor Necrosis Factor-α, Interleukin (IL)-6, and fibrinogen, were found to be elevated in PHPT patients. White blood count (WBC) values were similar in patients and controls in most studies, while for some markers derived from the full blood count significant differences were found between these groups. Correlations between PTH levels and several biomarkers, including IL-6, CRP and WBC, were also identified. Data on the impact of parathyroidectomy on inflammation parameters were conflicting.Conclusion: The findings from this systematic review suggest an association between chronic inflammation and primary hyperparathyroidism, underscoring the potential role of inflammation as a mediator of PHPT-related complications. Targeting inflammatory pathways may offer novel therapeutic strategies for mitigating systemic effects of PHPT and improving patient outcomes.

Whitish intraluminal esophageal masses might represent the endoscopic feature of a bezoar or a pedunculated tumor, most likely a fibrovascular polyp, without exclusion of other mesenchymal tumors (leiomyoma, lipoma, gastrointestinal stromal tumor, leiomyosarcoma, granular cell tumor). If a process of dystrophic calcification is also encountered the differential diagnosis can be a challenge even after histological analysis, as it is highlighted by our case. A 65-year-old female whom took lactate calcium tablets for 5 years presented with progressive dysphagia. A whitish esophageal mass with an appearance of a pharmacobezoar was detected at esophagoscopy. A pedunculated tumor was considered in the differential diagnosis, but the imagistic studies ruled out a pedicle. This intraluminal esophageal mass highly suggestive for a pharmacobezoar was endoscopically removed. The challenge of correct diagnosis was raised by histological examination performed after immersion into trichloracetic acid for decalcification. The identification of hyaline fibrous tissue, with numerous crystalline basophils deposits of minerals, rare fibrocytes and very few vessels brought in discussion a mesenchymal originating mass, most likely a fibrovascular polyp, even the pedicle was not detected. Based on our challenging and difficult to diagnose case we proposed an uncommon evolution: auto-amputation and calcification of an esophageal mesenchymal originating tumor (most likely a fibrovascular polyp).