[Show abstract][Hide abstract] ABSTRACT: Rare endocrine-metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism, energy and lipid metabolism, water metabolism, and syndromes with possible involvement of multiple endocrine glands, and neuroendocrine tumors. Taking advantage of the constitution of a study group on REMD within the Italian Society of Endocrinology, consisting of basic and clinical scientists, a document on the taxonomy of REMD has been produced.
Journal of endocrinological investigation 11/2014; · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gaucher disease is a relatively rare metabolic disease caused by the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Gaucher disease affects multiple organs, among which is the skeleton. Bone involvement occurs frequently in Gaucher disease, and is one of its most debilitating features, reducing the quality of life of patients. Bone status is an important consideration for treatment to ameliorate symptoms and reduce the risk of irreversible complications. We have conducted a systematic review of all the various aspects of Gaucher disease, focusing on different skeletal manifestations, pathophysiology of bone alterations, clinical symptoms, and current diagnostic and therapeutic approaches.
Calcified Tissue International 11/2014; · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular diseases, and some types of cancer. Recent interest has been focused on the biological activity of phenolic compounds present in extra virgin olive oils (EVOOs). Both in vivo and in vitro studies have shown that EVOO components have positive effects on metabolic parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet function, and antimicrobial activity. We have investigated the possible interactions between 2 extracts of extra virgin olive oil and estrogen receptor β (ERβ) in an in vitro model of colon cancer. The qualification and quantification of the components of the 2 samples tested showed that phenolic compounds-hydroxytyrosol, secoiridoids, and lignans-are the major represented compounds. EVOO extracts were tested on a colon cancer cell line engineered to overexpress ERβ (HCT8-β8). By using custom made Oligo microarray, gene expression profiles of colon cancer cells challenged with EVOO-T extracts when compared with those of cells exposed to 17β-estradiol (17β-E2). This study demonstrated that the EVOO extracts tested showed an antiproliferative effect on colon cancer cells through the interaction with estrogen-dependent signals involved in tumor cell growth. Specifically, the ability of EVOO extracts to inhibit cell proliferation was superimposable to the activation of the ERβ receptor, similar to what was observed after 17β-E2 challenge.
Nutrition and Cancer 09/2014; · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: Asymptomatic primary hyperparathyroidism (PHPT) is routinely encountered in clinical practices of endocrinology throughout the world. This report distills an update of current information about diagnostics, clinical features, and management of this disease into a set of revised guidelines. Participants: Participants, representing an international constituency, with interest and expertise in various facets of asymptomatic PHPT constituted four Workshop Panels that developed key questions to be addressed. They then convened in an open 3-day conference September 19-21, 2013, in Florence, Italy, when a series of presentations and discussions addressed these questions. A smaller subcommittee, the Expert Panel, then met in closed session to reach an evidence-based consensus on how to address the questions and data that were aired in the open forum. Evidence: Preceding the conference, each question was addressed by a relevant, extensive literature search. All presentations and deliberations of the Workshop Panels and the Expert Panel were based upon the latest information gleaned from this literature search. Consensus Process: The expert panel considered all the evidence provided by the individual Workshop Panels and then came to consensus. Conclusion: In view of new findings since the last International Workshop on the Management of Asymptomatic PHPT, guidelines for management have been revised. The revised guidelines include: 1) recommendations for more extensive evaluation of the skeletal and renal systems; 2) skeletal and/or renal involvement as determined by further evaluation to become part of the guidelines for surgery; and 3) more specific guidelines for monitoring those who do not meet guidelines for parathyroid surgery. These guidelines should help endocrinologists and surgeons caring for patients with PHPT. A blueprint for future research is proposed to foster additional investigation into issues that remain uncertain or controversial.
The Journal of clinical endocrinology and metabolism. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: Objective: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to provide an update on the use of diagnostic tests for this condition in clinical practice. Participants: This subgroup was constituted by the Steering Committee to address key questions related to the diagnosis of PHPT. Consensus was established at a closed meeting of the Expert Panel that followed. Evidence: Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting. Consensus Process: Consensus was achieved by a group meeting. Statements were prepared by all authors, with comments relating to accuracy from the diagnosis subgroup and by representatives from the participating professional societies. Conclusions: We conclude that: 1) reference ranges should be established for serum PTH in vitamin D-replete healthy individuals; 2) second- and third-generation PTH assays are both helpful in the diagnosis of PHPT; 3) normocalcemic PHPT is a variant of the more common presentation of PHPT with hypercalcemia; 4) serum 25-hydroxyvitamin D concentrations should be measured and, if vitamin D insufficiency is present, it should be treated as part of any management course; 5) genetic testing has the potential to be useful in the differential diagnosis of familial hyperparathyroidism or hypercalcemia.
The Journal of clinical endocrinology and metabolism. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: Deficiency of 25-hydroxyvitamin D [25(OH)D] is reported to be common in patients with rheumatoid arthritis (RA); data in patients with juvenile idiopathic arthritis (JIA) are inconsistent. We assessed serum 25(OH)D in children, adolescents and young adults with JIA, in order to identify the risk factors for vitamin D deficiency in patients with JIA.
[Show abstract][Hide abstract] ABSTRACT: In recent years, as knowledge regarding the etiopathogenetic mechanisms of bone involvement characterizing many diseases has increased and diagnostic techniques evaluating bone health have progressively improved, the problem of low bone mass/quality in children and adolescents has attracted more and more attention, and the body evidence that there are groups of children who may be at risk of osteoporosis has grown. This interest is linked to an increased understanding that a higher peak bone mass (PBM) may be one of the most important determinants affecting the age of onset of osteoporosis in adulthood. This review provides an updated picture of bone pathophysiology and characteristics in children and adolescents with paediatric osteoporosis, taking into account the major causes of primary osteoporosis (PO) and evaluating the major aspects of bone densitometry in these patients. Finally, some options for the treatment of PO will be briefly discussed.
[Show abstract][Hide abstract] ABSTRACT: Osteogenesis and bone remodeling are complex biological processes that are essential for the formation of new bone tissue and its correct functioning. When the balance between bone resorption and formation is disrupted, bone diseases and disorders such as Paget's disease, fibrous dysplasia, osteoporosis and fragility fractures may result. Recent advances in bone cell biology have revealed new specific targets for the treatment of bone loss that are based on the inhibition of bone resorption by osteoclasts or the stimulation of bone formation by osteoblasts. Bisphosphonates, antiresorptive agents that reduce bone resorption, are usually recommended as first-line therapy in women with postmenopausal osteoporosis. Numerous studies have shown that bisphosphonates are able to significantly reduce the risk of femoral and vertebral fractures. Other antiresorptive agents indicated for the treatment of osteoporosis include selective estrogen receptor modulators, such as raloxifene. Denosumab, a human monoclonal antibody, is another antiresorptive agent that has been approved in Europe and the USA. This agent blocks the RANK/RANKL/OPG system, which is responsible for osteoclastic activation, thus reducing bone resorption. Other approved agents include bone anabolic agents, such as teriparatide, a recombinant parathyroid hormone that improves bone microarchitecture and strength, and strontium ranelate, considered to be a dual-action drug that acts by both osteoclastic inhibition and osteoblastic stimulation. Currently, anti-catabolic drugs that act through the Wnt-β catenin signaling pathway, serving as Dickkopf-related protein 1 inhibitors and sclerostin antagonists, are also in development. This concise review provides an overview of the drugs most commonly used for the control of osteogenesis in bone diseases.
Clinics (São Paulo, Brazil) 06/2014; 69(6):438-446. · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Renal tumors are exceedingly rare in Multiple Endocrine Neoplasia type 1 (MEN1), a pleyotropic hereditary cancer disorder affecting the endocrine system. Herein we report a unique case of renal sarcomatoid carcinoma with concomitant ipsilateral non-secreting adrenal adenoma occurring in a young male MEN1 patient, previously operated for hyperparathyroidism and multiple pancreatic neuroendocrine neoplasms. Molecular analysis in the MEN1 locus at 11q13 showed loss of heterozygosity in the adrenal lesion, while kidney cancer was unrelated to MEN1 syndrome.
[Show abstract][Hide abstract] ABSTRACT: Multiple Endocrine Neoplasia type 4 (MEN4) is an autosomal dominant disorder, that presents with a spectrum of clinical manifestations overlapping with those of MEN1 syndrome. It is caused by inactivating mutations of CDKN1B gene, encoding for p27kip1 cyclin-dependent kinase 2 inhibitor, implicated in cell cycle control. Eight mutations of CDKN1B have been published in MEN4 patients. The aim of this study was to characterize the molecular basis of a case of MEN1-like syndrome with a neuroendocrine tumor and persistent primary hyperparathyroidism.
Clinical and biochemical and genetic evaluation was undertaken in the proband (a 53 year old Caucasian woman) and in one 34 year old son. The proband was operated for recurrent primary hyperparathyroidism. Sequence analysis of MEN1 and CDKN1B genes was performed on constitutional and parathyroid tissue DNA. Staining for p27 was carried out in parathyroid tissue. Results: No MEN1 mutations nor large deletions encompassing MEN1 gene on chromosome 11q13.1 could be detected in the proband. A germline frameshift mutation of CDKN1B (371delCT) was revealed, predicted to generate a truncated p27 protein. This mutation was confirmed on somatic DNA from the pathological parathyroid tissue, with the retention of the wild type allele.
We report a germline heterozygote frameshift mutation of CDKN1B gene in a Caucasian woman with a long clinical history of MEN1-like multiple endocrine tumors, along with the finding of the mutation in her son. This is the first report of positive CDKN1B mutation analysis in a male subject and also the first description of recurrent hyperparathyroidism in MEN4.
European Journal of Endocrinology 05/2014; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since low adherence to a long-term therapy results in a poor clinical outcome and significantly increases healthcare costs, adherence to the treatment of chronic disorders is an issue of great interest. This is particularly true of the treatment of osteoporosis (OP).
[Show abstract][Hide abstract] ABSTRACT: Bone tissue engineering represents one of the most challenging emergent fields for scientists and clinicians. Current failures of autografts and allografts in many pathological conditions have prompted researchers to find new biomaterials able to promote bone repair or regeneration with specific characteristics of biocompatibility, biodegradability and osteoinductivity. Recent advancements for tissue regeneration in bone defects have occurred by following the diamond concept and combining the use of growth factors and mesenchymal stem cells (MSCs). In particular, a more abundant and easily accessible source of MSCs was recently discovered in adipose tissue. These adipose stem cells (ASCs) can be obtained in large quantities with little donor site morbidity or patient discomfort, in contrast to the invasive and painful isolation of bone marrow MSCs. The osteogenic potential of ASCs on scaffolds has been examined in cell cultures and animal models, with only a few cases reporting the use of ASCs for successful reconstruction or accelerated healing of defects of the skull and jaw in patients. Although these reports extend our limited knowledge concerning the use of ASCs for osseous tissue repair and regeneration, the lack of standardization in applied techniques makes the comparison between studies difficult. Additional clinical trials are needed to assess ASC therapy and address potential ethical and safety concerns, which must be resolved to permit application in regenerative medicine.
World journal of stem cells. 04/2014; 6(2):144-152.
[Show abstract][Hide abstract] ABSTRACT: Our objective was to evaluate longitudinally the main bone mass and quality predictors in young juvenile idiopathic arthritis (JIA) patients using lumbar spine dual energy X-ray absorptiometry (DXA) scan, radius peripheral quantitative computed tomography (pQCT), and phalangeal quantitative ultrasonography (QUS) at the same time.
In total, 245 patients (172 females, 73 males; median age 15.6 years: 148 oligoarticular, 55 polyarticular, 20 systemic, and 22 enthesitis-related-arthritis (ERA) onset) entered the study. Of these, 166 patients were evaluated longitudinally. Data were compared with two age- and sex- matched control groups.
In comparison to controls, JIA patients, but not with ERA, had a reduced spine bone mineral apparent density (BMAD) standard deviation score (P < 0.001) and musculoskeletal deficits, with significantly lower levels of trabecular bone mineral density (TrabBMD) (P < 0.0001), muscle cross-sectional area (CSA) (P < 0.005), and density-weighted polar section modulus (SSIp) (P < 0.05). In contrast, JIA showed fat CSA significantly higher than controls (P < 0.0001). Finally, JIA patients presented a significant reduced amplitude-dependent speed of sound (AD-SoS) (P < 0.001), and QUS z-score (P < 0.005).Longitudinally, we did not find any difference in all JIA patients in comparison to baseline, except for SSIp value that normalized. Analyzing the treatments, a significant negative correlation among spine BMAD values, TrabBMD, AD-SoS and systemic and/or intra-articular corticosteroids, and a positive correlation among TNF-alpha-blocking agents and spine BMAD, TrabBMD, and AD-SoS were observed.
JIA patients have a low bone mass that, after a first increase due to the therapy, does not reach the normal condition over time. The pronounced bone deficits in JIA are greater than would be expected due to reduction in muscle cross-sectional area. Thus, bone alterations in JIA likely represent a mixed defect of bone accrual and lower muscle forces.
Arthritis research & therapy 03/2014; 16(2):R83. · 4.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The lack of a continuous cell line of epithelial parathyroid cells able to produce parathyroid hormone (PTH) has hampered the studies on in vitro evaluation of the mechanisms involved in the control of parathyroid cell function and proliferation. The PT-r cell line was first established from rat parathyroid tissue in 1987, but these cells were known to express the parathyroid hormone-related peptide (Pthrp) gene, but not the Pth gene. In an attempt to subclone the PT-r cell line, a rat parathyroid cell strain was isolated and named PTH-C1. During 3 years, in culture, PTH-C1 cells maintained an epithelioid morphology, displaying a diploid chromosome number, a doubling time around 15 h during the exponential phase of growth, and parathyroid functional features. PTH-C1 cell line produces PTH and expresses the calcium sensing receptor (Casr) gene and other genes known to be involved in parathyroid function. Most importantly, the PTH-C1 cells also exhibit an in vitro secretory response to calcium. Altogether these findings indicate the uniqueness of the PTH-C1 cell line as an in vitro model for cellular and molecular studies on parathyroid physiopathology.
[Show abstract][Hide abstract] ABSTRACT: To update the Diagnostic-Therapeutic-Healthcare Protocol (Protocollo Diagnostico-Terapeutico-Assistenziale, PDTA) created by the U.E.C. CLUB (Association of the Italian Endocrine Surgery Units) during the I Consensus Conference in 2008.
In the preliminary phase, the II Consensus involved a selected group of experts; the elaboration phase was conducted via e-mail among all members; the conclusion phase took place during the X National Congress of the U.E.C. CLUB. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up.
The PDTA for parathyroid surgery approved by the II Consensus Conference (June 2013) is the official PDTA of the U.E.C. CLUB.
Journal of endocrinological investigation 02/2014; 37(2):149-65. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate bone status in children born from mothers followed for autoimmune diseases and treated during pregnancy with low molecular weight heparin (LMVH) and/or prednisone.
Annals of the Rheumatic Diseases 01/2014; 12:47. · 9.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by x-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA, n=14,260), velocity of sound (VOS, n=15,514) and BMD (n=4,566) in 13 discovery cohorts. Independent replication involved 7 cohorts with GWA data (in silico n=11,452) and new genotyping in 15 cohorts (de novo n=24,902). In combined random effects meta-analysis of the discovery and replication cohorts, 9 SNPs had genome-wide significant (p<5×10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708), and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (p<8.23×10(-14)). In meta-analyses involving 25 cohorts with up to 14,985 fracture cases, six of 10 SNPs associated with heel bone properties at p<5×10(-6) also had the expected direction of association with any fracture (p<0.05), including 3 SNPs with p<0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007), and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
Human Molecular Genetics 01/2014; · 7.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The endocrine system is frequently altered after a major burn trauma. Besides the endocrine response to stress characterized by hypercortisolism, several hypothalamus–hypophysis–target gland axes are rapidly perturbed within a few days. These alterations can persist in the long term and deserve an appropriate treatment. Disturbances in water clearance and glucidic metabolism are also common and need to be diagnosed and corrected to decrease morbidity in such patients. Bone and mineral metabolism is deeply compromised and requires correction of mineral abnormalities in order to improve symptoms and prevent bone loss. No large prospective and/or intervention trials are available to date to elaborate age-related, evidence-based recommendations to monitor and treat burn-related endocrine alterations.
Expert Review of Endocrinology & Metabolism 01/2014; 9(1).