Arterial Stiffness and Decreased Bone Buffering Capacity in Hemodialysis Patients
Kidney DiseaseHypercalcemiaRenal patients have an increased risk for cardiovascular complications. There is also increased vascular calcification and bone metabolism is similarly abnormal in patients with chronic kidney disease. In dialysis patients frequent episodes of hypercalcaemia occur. In a healthy bone structure those episodes of hypercalcemia are buffered by the bone. The absence of bone buffering capacity in dialysis patients can be a mechanism for vascular calcifications.
S0308 Zoledronate or Ibandronate in Preventing Bone Problems in Women With Stage IV Breast Cancer...
Breast CancerHypercalcemia of Malignancy2 moreRATIONALE: Zoledronate and ibandronate may prevent or help relieve bone pain and other symptoms caused by bone metastases. It is not yet known whether zoledronate is more effective than ibandronate in preventing bone problems caused by bone metastases due to breast cancer. PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works compared to ibandronate in preventing bone problems in women with stage IV breast cancer that has spread to the bone.
One Week Comparison Study of PTH and PTHrP Infusions
OsteoporosisHypercalcemia of Malignancy3 moreThis is a dose escalation study to determine the maximum tolerable dose of Parathyroid Hormone-related Protein, PTHrP, or Parathyroid Hormone, PTH, that can be given safely over one week in healthy African-American volunteers. The investigators plan to infuse low doses of intravenous PTHrP or PTH to determine if it leads to a sustained and progressive suppression of bone formation as occurs in humoral hypercalcemia of malignancy (HHM) or an increase in bone formation as occurs in hyperparathyroidism (HPT). Additionally, the investigators will assess the direct influence of PTHrP and PTH on vitamin D metabolism, markers of bone turnover, and fractional excretion of calcium. These results will be compared to previous studies of Caucasian volunteers.
Primary Hyperparathyroidism (PHPT): Early Effect of Vitamin D
Primary HyperparathyroidismHypercalcemia3 morePrimary hyperparathyroidism (PHPT) is a common disease that occurs in 1 in 10,000 people every year. In the presence of this condition, the parathyroid glands produce excessive amounts of parathyroid hormone (PTH), which regulates calcium levels. The high levels of parathyroid hormone remove too much calcium from bones, and then deposit the excess calcium in the blood, which is then filtered into the urine by the kidneys. Bone health is threatened by excess calcium loss which weakens bone structure. Other affected organs include the skeleton (calcium loss leads to a "weakening" of the skeleton), and the kidneys (high blood calcium can lead to kidney stones). It is now evident that the majority of patients with even mild Primary Hyperparathyroidism are vitamin D deficient. In 2009, new international guidelines for the management of asymptomatic PHPT direct physicians to measure 25-hydroxyvitamin D (D3 or 25-OHD) in all patients, and to replete the reserve of vitamin D when the level is low (< 20 ng/ml). However, no recommendations for vitamin D repletion are given, because of limited data regarding the effects of vitamin D repletion, appropriate dosing and safety. Therefore, there is an urgent need for data upon which to base such recommendations, as well as are data on the effects of such treatment upon bones. Subjects with low vitamin D3 levels will be selected for this trial. They will be given enough vitamin D3 to raise their low blood levels from a low to a normal range. The assessments in this study, including the quadruple label bone biopsy, will allow us to document the short term effects of administering vitamin D3 on changes in bone. All participants enrolled in this trial will be vitamin D3 deficient. Participants will take an antibiotic (tetracycline) 4 times a day to mark the starting point from which bone changes will be assessed. After 3 days of tetracycline, a 12 week course of vitamin D3 or placebo will be initiated. Six of 7 participants will receive the study drug (active vitamin D3), while 1 in 7 will receive a placebo (sugar pill). Ten weeks later, another 3-day course of tetracycline will be given. At the end of 12 weeks, a bone biopsy will be done. A small piece of bone (about the size of a pencil eraser) will be removed from the hip (iliac crest). The bone will be analyzed to determine the effect of vitamin D3 on primary hyperparathyroidism. There will be 4 study visits: Screening, Baseline, Week 8, and Week 12 when the bone biopsy will be performed. Study Procedures: Medical and Social History Blood tests (drawn at the study center and local Quest Lab) 24-Hour urine collection for calcium and creatinine excretion Abdominal X-ray (to assess for kidney stones) Transiliac crest Bone Biopsy
Calcitonin Pre-treatment to Improve SPECT-CT Sensitivity
Primary HyperparathyroidismHypercalcemiaPatients with biochemically confirmed primary hyperparathyroidism and non-localizing SPECT-CT exam within the past year will be included. Subjects will be treated with calcitonin to lower calcium levels immediately prior to reimaging. The goal of this study is to determine whether lowering calcium will improve uptake/retention of sestamibi and improve sensitivity of SPECT-CT to localize parathyroid adenoma.
Search for New Genetic Causes of Hypercalcemia by Massively Parallel Sequencing of a Genes Panel...
HypercalcemiaHypercalcemia, whether chronic or acute, exposes the patient to potentially serious complications (arrhythmias, nephrolithiasis, nephrocalcinosis, ...). Prevention relies primarily on effective etiological necessary for taking matched load. Under the French reference center for rare disorders of calcium and phosphorus, the investigators looked for mutations in the coding sequence of the CYP24A1 gene (encoding the enzyme responsible for the breakdown of vitamin D), among patients with hypercalcemia without hyperparathyroidism with hypersensitivity to vitamin D. However, only 25% of these patients have a genetic anomaly suggesting the involvement of other genes (Molin et al. 2015). Recently our team, combined with Kaufmann et al. (2014 JCEM) validated the interest of the determination of metabolites of vitamin D by liquid chromatography-tandem mass spectrometry (LC-MS / MS), as biological pre-screening stage for patients with hypercalcemia. The objective of this project is to complement the molecular and biochemical studies of patients without mutation of the coding sequence of CYP24A1, in a gene candidate approach using massively parallel sequencing (MPS) which allows to study a panel of gene potentially involved in disorder of metabolism of calcium and phosphorus. Highlighted variations will be tested in silico, and if possible in vitro. The investigators will also use LC-MS / MS to evaluate in vivo the effects of these variations on the metabolism of vitamin D, to develop a genotype / phenotype correlation. The work carried out within the Genetics Department Caen University Hospital in collaboration with physicians of the rare disease reference center of the metabolism of calcium and phosphorus should identify new genetic mechanisms underlying hypercalcemia. At the time of development of personalized medicine, it will adapt the therapy in patients at risk for metabolic complications and / or kidney following administration of vitamin D and finally to offer genetic counseling.
Rate of Termination of Premixed Parenteral Nutrition (PN) in Surgical Patients Secondary to High...
HyperphosphatemiaHyperkalemia2 moreIntroduction: Various commercial premixed parenteral nutrition (PN) solutions have been introduced to clinical practice in 3-compartment large volume bags. Olimel N9E is the formulary premixed PN formula at King Faisal Specialist Hospital and Research Centre (KFSH & RC). The commercial premixed PN was associated with a significant cost reduction compared to the compounded PN, with lower incidence of infectious complications, compared to the compounded PN formula. Electrolyte irregularities are commonly encountered with PN use. Patients who develop high serum potassium, magnesium or phosphate levels while receiving premixed PN are shifted to a compounded PN with lower electrolyte content. This study aims to describe the incidence of shifting of premixed PN to a compounded PN secondary to high serum electrolytes in surgical patients receiving commercial premixed PN. Methods: This is a prospective, cohort, study, to be conducted at KFSH & RC, Riyadh. This study is proposed to commence after obtaining the approval of the Research Ethical Committee at KFSH & RC. Patients enrolment will start after the approval at KFSH & RC, by data collection phase, that might extend for a suspected 6-month until achieving the target sample size of 55 patients. The analysis phase will follow and elapse for 2 months. This is followed by 2 months to get the initial abstract. All patients will have their potassium, magnesium, calcium and phosphorus levels assessed daily in the morning for the first 7 days of PN initiation. After the first week of PN support, according to the routine laboratories, electrolytes will be assessed at a minimum of three times a week thereafter while on PN. There will be no extra laboratory work obtained for the study purpose. The incidence of shifting from premixed PN to compounded PN will be assessed and reported. A description of the characteristics of patients who develop high serum level of electrolytes will be undertaken using regression analysis.
Preoperational Fine Needle Aspiration of Pathological Parathyroid Gland
Parathyroid AdenomaHypercalcemiaIdentification and localization of pathological parathyroid gland before parathyroidectomy is traditionally done by a combination of two methods: ultrasound and sestamibi scan. The investigators would like to show that one exam that includes ultrasound and fine needle aspiration of the parathyroid gland for parathyroid hormone level is as accurate as the traditional method.
Lipid and Glycogen Metabolism in Patients With Impaired Glucose Tolerance and Calcium Sensing Receptor...
Type 2 Diabetes MellitusPrediabetes (Insulin Resistance4 moreBackground: Type 2 diabetes mellitus is a main risk factor for cardiovascular disease and heart failure, in part due to diabetic cardiomyopathy. However, the association between intracellular lipid accumulation and (myocardial) functional impairment is likely more complex than originally imagined. Recent studies suggest that not fat per se, but the content of saturated or unsaturated fatty acids might predict the development of cardiac steatosis and myocardial dysfunction. In addition skeletal muscle and hepatic glycogen metabolism is impaired in patients with diabetes mellitus. Data from animal experiments suggest a relevant role of myocardial glycogen stores in ischemic preconditioning. Due to methodological limitations so far data on myocardial glycogen stores and myocardial lipid composition in humans are missing. Hypothesis: In addition to total ectopic lipid deposition in the myocardium, myocardial lipid composition, i.e. the relative abundance of saturated and unsaturated fatty acids, and impaired myocardial glycogen metabolism may play an important role in the development cardiac lipotoxicity leading to diabetic cardiomyopathy. Pancreatic endocrine function and myocardial morphology and function is altered in patients with heterozygote inactivating mutations of the CaSR-gene / FHH. Aims: Metabolic virtual biopsy of the myocardium for identification of specific patterns of intracellular lipid composition and myocardial glycogen metabolism as possible critical determinants of metabolic cardiomyopathy Characterization of the metabolic interplay between the myocardium, skeletal muscle, liver and adipose tissues in different stages of development of type 2 diabetes compared to patients with calcium sensing receptor mutation Methods: 1H/13C and 31P magnetic resonance spectroscopy and imaging for measurements of myocardial, skeletal and liver lipid and glycogen content, abdominal adipose tissue distribution and composition, ATP synthesis and myocardial functional parameters Mixed meal tolerance tests to trace the postprandial partitioning of substrates between insulin sensitive tissues (myocardium, skeletal muscle, liver, adipose tissue). Hyperinsulinemic-hyperglycemic glucose clamp (HHC) with enrichment of the infused glucose with the stable isotope [1-13C]glucose to trace the incorporation of circulating glucose into myocardial glycogen in healthy insulin sensitive volunteers, prediabetic insulin resistant volunteers with impaired glucose tolerance, healthy subjects, patients suffering from type 2 diabetes mellitus, patients suffering from type 1 diabetes and patients with heterozygote mutation in calcium sensing receptor.
Insulin Resistance in Primary Hyperparathyroidism
HyperparathyroidismDiabetes1 moreThe aims of this study is to analyse if insulin resistance in primary hyperparathyroidism (pHPT) is normalised after parathyroid adenomectomy and if glucose tolerance test may be useful as a diagnostic tool by predicting potential improvement of insulin sensitivity after biochemical cure of pHPT.