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

CONTEXT: Normocalcaemic hypoparathyroidism (NHYPO) is characterized by low levels of parathyroid hormone (PTH) with normal levels of calcium. There is little in the current literature on this disease, with only two studies published on its prevalence, while 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. Five-year follow-up. 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, and the rest had 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.

Normocalcaemic hyperparathyroidism and primary hyperparathyroidism: least significant change 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 deviatio 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.

Hemochromatosis gene mutations and treatment of anemia in patients on hemodialysis.

Hemochromatosis causes iron overload by enhanced intestinal absorption. This study examined erythropoietin and intravenous (i.v.) iron requirements in hemodialysis (HD) patients with HFE mutations. Patients on HD for > 90 days with no cause of anemia except chronic kidney disease were tested for HFE mutations (H63D and C282Y). Intravenous iron and erythropoietin doses were adjusted to achieve recommended targets. Monthly hemoglobin (Hb), ferritin, mean corpuscular volume, mean cell hemoglobin, erythropoietin, and i.v. iron doses for 3 consecutive months were averaged. Of 172 patients, 71 (41.3%) had > or = 1 HFE mutation: 24 (14%) C282Y heterozygotes, 40 (23.3%) H63D heterozygotes, 5 compound heterozygotes, and 2 homozygotes. Comparing patients with > or = 1 HFE mutation to those without mutations showed no significant difference in Hb or serum ferritin. There was a trend toward lower median weekly erythropoietin dose in patients with > or = 1 HFE mutation (94.0 vs. 135.4 U/kg body weight; P=0.13). There was no difference in median weekly i.v. iron dose (1.0 vs. 0.9 mg/kg body weight; P=0.56). Comparing the 30 patients with a C282Y mutation to patients without HFE mutations produced similar results. Comparing the 47 patients with an H63D mutation, with those without HFE mutations, no discernable trend was observed. In this study, patients with HFE gene mutations on HD for established renal failure do not require less iron supplementation to achieve recommended Hb targets. We observed a trend toward lower erythropoietin requirement in patients possessing C282Y mutations. Larger studies may clarify the role of HFE mutations, regulators of iron metabolism and erythropoiesis in chronic kidney disease.

Acute inflammatory response does not affect erythrocyte concentrations of copper, zinc and selenium.

BACKGROUND & AIMS: Measuring the nutritional status of trace elements in plasma is invalidated in the presence of a systemic inflammatory response. We examined the potential of erythrocytes to assess copper, zinc and selenium status in such situations. METHODS: Venous blood samples were withdrawn pre-operatively and at 12, 24, 48, 72 and 168 h post-operatively from 11 patients (6 males and 5 females) who were admitted for elective knee arthroplasty. C-reactive protein, albumin, copper, zinc, selenium and iron were measured in plasma and erythrocytes. RESULTS: Plasma zinc and selenium concentrations fell significantly: 95% confidence intervals (CI)=-32% to -44% and -22% to -36%, respectively. Copper concentrations fell transiently and then increased significantly: CI=12-43%. No significant changes were seen in trace element concentrations in erythrocytes expressed either as a ratio of haemoglobin or iron concentration. Erythrocyte iron levels correlated significantly with haemoglobin (r=0.93). CONCLUSIONS: Plasma concentrations of copper, zinc and selenium are unreliable markers of status in patients with an acute inflammatory response. Erythrocyte concentrations of these trace elements may provide a more reliable measure in long-term studies of patients with a chronic systemic inflammatory response. Iron can be used instead of haemoglobin as the denominator when expressing erythrocyte concentrations of trace elements.