The prevalence and natural history of normocalcaemic hyperparathyroidism and hypoparathyroidism

Normocalcaemic hyperparathyroidism (NPHPT) is characterised by persistently normal calcium levels, elevated PTH values on at least two consecutive measurements, after excluding other causes of secondary hyperparathyroidism. The prevalence of the disease in the literature varies significantly due to various definitions used; it is reported to be between 0.1 and 8.9%. The data on the natural history of this disease are sparse and inconclusive. Normocalcaemic hypoparathyroidism (NHYPO) is characterised by persistently low levels of parathyroid hormone (PTH) with normal levels of calcium. There is little in current literature on this disease, with only two studies published on its prevalence whilst its natural history remains relatively unknown. The aims of this study were: to identify the prevalence of NPHPT in a UK referral population using the international criteria and study the natural history of this disorder and the variability of serum calcium; to compare the variability of calcium in NPHPT and PHPT; to identify the prevalence of NHYPO and to study the natural history of the disorder and the variability of serum calcium. The prevalence of NPHPT in our UK referral population was found to be low. NPHPT patients often have episodes of hypercalcemia, so they probably suffer from PHPT. The variability of NPHPT and PHPT patients is similar. The prevalence of NHYPO calculated from this UK referral population is lower when compared to results from previous studies. NHYPO patients often have episodes of hypocalcaemia with some cases having no apparent reason for calcium levels below the reference range. The next steps are to find out the cause of this biochemical abnormality and the consequences, if any

Reference interval for albumin‐adjusted calcium based on a large UK population

Context: Primary hyperparathyroidism is a common condition and results in hypercalcaemia, especially in older women. Thus, it is critical to obtain a robust estimate for the upper limit of the reference interval for albumin‐adjusted serum calcium in the general population. The current reference interval in use in the UK (Pathology Harmony range, 2.20 to 2.60 mmol/L) was based on a consensus. Objectives: To establish a reference interval for albumin‐adjusted serum calcium in men and women. Design: Cross‐sectional study of men and women who did not have chronic kidney disease or vitamin D deficiency; outliers were identified statistically and then rejected and then a 99% reference interval was calculated. Patients: 502 524 men and women aged 40 to 69 years from the UK Biobank Study. Measurements: Serum total calcium, albumin, 25‐hydroxyvitamin D, estimated glomerular function (eGFR). Results: We developed an equation for albumin‐adjusted serum calcium and applied it to 178 377 men and women who did not have chronic kidney disease or vitamin D deficiency. We identified 2962 (1.7%) as outliers, and when excluded, we report a 99% reference interval of 2.19 to 2.56 mmol/L (8.76 to 10.24 mg/dL). We found that for older (55‐69 years) and younger women (40‐55 years) the upper limits were 2.59 mmol/L and 2.57 mmol/L and that for all men, the upper limit was 2.55 mmol/L. Conclusions: We have established an upper limit of the reference range for older women that would identify all high outliers (2.60 mmol/L and above). The upper limit for young women and for men is lower, at 2.57 and 2.55 mmol/L respectively. The current reference interval in use has to be updated and improved based on these findings. These upper limits may prove helpful for identifying hypercalcaemic disorders like primary hyperparathyroidism in clinical practice

Normocalcaemic hyperparathyroidism (NPHPT) and primary hyperparathyroidism (PHPT): Least significant change (LSC) for adjusted serum calcium

Introduction: The least significant change (LSC) is a term used in individuals in order to evaluate whether one measurement has changed significantly from the previous one. It is widely used when assessing bone mineral density (BMD) scans. To the best of our knowledge, there no such estimate available in the literature for patients with disorders of calcium metabolism. Our aim was to provide an estimate of the least significant change for albumin-adjusted calcium in patients with normocalcaemic hyperparathyroidism (NPHPT) and primary hyperparathyroidism (PHPT). Methods: We used the within subject standard deviation calculated in a population of NPHPT and PHPT patients and multiplied it by 2.77. Results: The LSC for NPHPT and PHPT were found to be 0.25 and 0.24 mmol/L respectively (1.00 and 0.96 mg/dL). In clinical practice, the value of 0.25 mmol/L could be used. Discussion: The least significant change given, could be used in two ways in these patients. First, it gives a range to which values are expected. This can provide some reassurance for the patient and the physician in cases of intermittent hypercalcaemia. Moreover, it can be a marker of whether an individual has an actual significant change of his calcium after parathyroid surgery

Normocalcemic hyperparathyroidism : study of its prevalence and natural history

Context Normocalcemic hyperparathyroidism (NPHPT) is characterized by persistently normal calcium levels and elevated parathyroid hormone (PTH) values, after excluding other causes of secondary hyperparathyroidism. The prevalence of the disease varies greatly and the data on the natural history of this disease are sparse and inconclusive. Objectives The objectives of this study are to describe the prevalence of NPHPT and its natural history in a referral population and to compare the variability of serum calcium with a group of patients with primary hyperparathyroidism (PHPT). Design A retrospective study was conducted over 5 years. Setting The setting for this study was a metabolic bone referral center. Patients A total of 6280 patients were referred for a bone mineral density measurement (BMD). Main Outcome Measures The prevalence and natural history of NPHPT and variability of calcium were the main outcome measures. Results We identified NPHPT patients using data from the day of the BMD measurement. We excluded patients with low estimated glomerular filtration rate (eGFR) or vitamin D, or with no measurements available. Based on the evaluation of their medical files, we identified 11 patients with NPHPT (prevalence 0.18%). Only 4 patients had consistent normocalcemia throughout their follow-up, with only 2 also having consistently high PTH. None had consistently normal eGFR or vitamin D. Intermittent hypercalcemia was present in 7 of the 11 NPHPT patients. The mean adjusted calcium was found to be significantly lower in the NPHPT group compared with the PHPT group but higher than the control group. PTH was similar for NPHPT and PHPT. These 2 groups had similar variability in serum calcium. Conclusions NPHPT patients often have episodes of hypercalcemia. We believe that NPHPT is a mild form of PHPT

The prevalence and natural history of normocalcaemic hypoparathyroidism in a United Kingdom referral population

Context Normocalcaemic hypoparathyroidism (NHYPO) is characterised by persistently low levels of parathyroid hormone (PTH) with normal levels of calcium. There is little in current literature on this disease, with only two studies published on its prevalence whilst its natural history remains relatively unknown. Objectives to identify the prevalence of NHYPO in a UK referral population and to study the natural history of the disorder. Design Retrospective study. Follow up five years Patients 6280 patients referred for a BMD measurement in a Metabolic Bone referral centre Measurements Prevalence of NHYPO and variability of calcium Results Based on laboratory results on the index day, 22 patients with NHYPO were identified. Four patients were excluded due to non‐PTH induced hypocalcaemia and unconfirmed data. The final prevalence was 0.29%. Only 67% had persistent normocalcaemia, the rest having intermittent hypocalcaemia. Two of these patients also had persistently low PTH on two occasions. Most of the patients had one PTH measurement available. No patient developed permanent hypoparathyroidism. Conclusions The prevalence calculated from this UK referral population is lower when compared to results from previous studies. NHYPO patients often have episodes of hypocalcaemia with some cases having no apparent reason for calcium levels below the reference range

Mechanisms underlying the endothelium-dependent vasodilatory effect of an aqueous extract of Elaeis guineensis Jacq. (Arecaceae) in porcine coronary artery rings

This study was undertaken to investigate the vasodilatory effect of an aqueous extract of Elaeis guineensis Jacq (EGE) in the porcine coronary artery and elicit its possible mechanism(s) of action. Vascular effects of crude extract of dried and powdered leaves of Elaeis guineensis were evaluated on isolated coronary arteries on organ chambers. Determination of eNOS expression and the phosphorylation level of eNOS were  determined by Western blot analysis. In the presence of indomethacin,  EGE caused pronounced relaxations in endothelium-intact but not in endothelium-denuded coronary artery rings. Relaxations to EGE were significantly reduced by Nω-nitro-L-arginine (L-NA, a competitive inhibitor of NO synthase), slightly but not significantly by charybdotoxin plus apamin (two potent inhibitors of EDHF-mediated responses) and abolished by the combination of L-NA and charybdotoxin plus apamin. Relaxations to EGE were abolished by the membrane permeant, SOD mimetic, MnTMPyP, and significantly reduced by wortmannin, an inhibitor of PI3-kinase. Exposure of endothelial cells to EGE increased the phosphorylation level of eNOS at Ser1177 in a time and concentration-dependent manner. MnTMPyP abolished the EGE-induced phosphorylation of eNOS. In conclusion, the obtained data indicate that EGE induces pronounced endothelium-dependent relaxations of the porcine coronary artery, which involve predominantly NO. The stimulatory effect of EGE on eNOS involves the redox-sensitive phosphorylation of eNOS at Ser1177 most likely via the PI3-kinase pathway

Cytotoxic Effect of Ethanol Extract of Convolvulus arvensis L (Convolvulaceae) on Lymphoblastic Leukemia Jurkat Cells

Purpose: To evaluate the cytotoxic effect of ethanol extract of aerial parts of Convolvulus arvensis against lymphoblastic leukemia, Jurkat cells.Methods: The aerial parts of C. arvensis were collected, identified, powdered and soaked in ethanol. The extract was filtered and evaporated, and the residue assessed for cytotoxic activity in Jurkat cell line. The cells were exposed to different concentrations (10, 25, 50, 75 and 100 μg/mL) of the extract to determine cell viability, cell proliferation, apoptosis using Trypan blue exclusion assay, 3-(4,5- dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and fluorescent activated cell sorter (FACS) analysis, respectively.Results: Trypan blue exclusion assay and MTS assay results indicate that the ethanol extract decreased the number of living cells in a concentration-dependent fashion. The results of FACS analysis showed that the lowest concentration of the extract (10 μg/mL) was most effective for the induction of apoptosis as it induced maximum apoptosis (85.34 %) and the highest concentration (100 μg/mL) was less effective as it induced less apoptosis (53.70 %) in Jurkat cells (p < 0.05).Conclusion: The ethanol extract of C. arvensis has significant cytotoxic activity against the selected cancer cell line. Furthermore, apoptotic effect was more prominent at lower doses and necrosis at higher doses of the extract.Keywords: Convolvulus arvensis; (MTS) 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium assay; Trypan blue exclusion assay, Apoptosis, Necrosi