Calcium requests in a primary care; An observational audit of biochemical requests and frequency of abnormal results.

BACKGROUND/AIMS: This aim of this audit was to assess the extent of serum calcium testing and the frequency of hypercalcaemia in the primary care setting. We also assessed the appropriateness of subsequent investigations with repeat serum calcium and PTH testing if hypercalcaemia was identified. METHODS: All laboratory requests for adjusted calcium and PTH samples sent from primary care in Glasgow were analysed over a 12 month period. This covered approximately 125 GP practices and a patient population of over 590,000. RESULTS: There were 78,845 requests for adjusted calcium and 2053 PTH requests from 62,745 patients aged 16-105 years (median age 57, IQ range 30 years). Of these requests 1423 (2.3%) of patients had biochemical evidence of hypercalcaemia (adjusted calcium ≥ 2.61 mmol/L). Of the 1423 patients with hypercalcaemia, 368 patients (45.8%) had a single raised calcium level that was within the normal range on repeat testing. Of the 400 patients with persistent hypercalcaemia on 2 or more samples, 210 (52.5%) had a PTH measured. Eight patients had a PTH < 2.0 pmol/L, whilst 202 (96.1%) had a PTH ≥ 2.0 pmol/L (range 2.1-106.1 pmol/L). CONCLUSIONS: Serum calcium was checked in 10.6% of the population per year within primary care. In the 2.4% with a raised calcium on initial testing, approximately half (45.8%) will normalise on repeat testing. Of those who remained persistently hypercalcaemic, only half (52.5%) had a PTH measured and the majority (96.1%) were in keeping with primary hyperparathyroidism being the most common cause of hypercalcaemia.

The effect of magnesium administration on erythrocyte transketolase activity in alcoholic patients treated with thiamine.

BACKGROUND AND AIMS: Chronic alcoholic patients are at increased risk of developing deficiencies of thiamine and magnesium. Thiamine is an essential co-factor for a number of enzymes involved in carbohydrate metabolism and requires optimal levels of magnesium for biological function. However, whilst thiamine supplementation is well established for the treatment of alcoholic patients, the importance of magnesium is often overlooked. We describe the effect of concurrent thiamine and magnesium administration on the activity of the thiamine-dependent enzyme erythrocyte transketolase in a cohort of chronic alcoholic patients. METHODS: Baseline erythrocyte transketolase activities were measured on blood samples collected from 36 chronic alcoholic patients presenting acutely to the Accident and Emergency department. Patients received either intravenous Pabrinex (thiamine) supplemented with magnesium sulphate (n = 18) or Pabrinex only (n = 18). Post-treatment bloods were collected for re-assessment of erythrocyte transketolase activity. The change in transketolase activities (pre-vs. post-treatment) between the two patient groups were compared by Mann-Whitney U test. RESULTS: The increase in transketolase activity following treatment in the cohort receiving Pabrinex supplemented with magnesium sulphate was significantly greater (p = 0.018) than that produced in the cohort receiving Pabrinex alone. CONCLUSION: In the acute management of a sample of chronic alcoholic patients, those receiving magnesium sulphate with Pabrinex have higher increases in erythrocyte transketolase activity compared with those receiving Pabrinex alone. We conclude that concurrent magnesium administration with Pabrinex may be required for enabling full efficacy of Pabrinex treatment, as demonstrated by its positive effect on erythrocyte transketolase activity.

Vitamin D insufficiency and the blunted PTH response in established osteoporosis: the role of magnesium deficiency.

INTRODUCTION: Vitamin D insufficiency is common, however within individuals, not all manifest the biochemical effects of PTH excess. This further extends to patients with established osteoporosis. The mechanism underlying the blunted PTH response is unclear but may be related to magnesium (Mg) deficiency. The aims of this study were to compare in patients with established osteoporosis and differing degrees of vitamin D and PTH status : (1) the presence of Mg deficiency using the standard Mg loading test (2) evaluate the effects of Mg loading on the calcium-PTH endocrine axis (3) determine the effects of oral, short term Mg supplementation on the calcium-PTH endocrine axis and bone turnover. METHODS: 30 patients (10 women in 3 groups) were evaluated prospectively measuring calcium, PTH, Mg retention (Mg loading test), dietary nutrient intake (calcium, vitamin D, Mg) and bone turnover markers (serum CTX & P1CP). Multivariate analysis controlling for potential confounding baseline variable was undertaken for the measured outcomes. RESULTS: All subjects, within the low vitamin D and low PTH group following the magnesium loading test had evidence of Mg depletion [mean(SD) retention 70.3%(12.5)] and showed an increase in calcium 0.06(0.01) mmol/l [95% CI 0.03, 0.09, p=0.007], together with a rise in PTH 13.3 ng/l (4.5) [95% CI 3.2, 23.4, p=0.016] compared to baseline. Following oral supplementation bone turnover increased: CTX 0.16 (0.06) mcg/l [95%CI 0.01, 0.32 p=0.047]; P1CP 13.1 (5.7) mcg/l [95% CI 0.29, 26.6 p=0.049]. In subjects with a low vitamin D and raised PTH mean retention was 55.9%(14.8) and in the vitamin replete group 36.1%(14.4), with little change in both acute markers of calcium homeostasis and bone turnover markers following both the loading test and oral supplementation. CONCLUSIONS: This study confirms that in patients with established osteoporosis, there is also a distinct group with a low vitamin D and a blunted PTH level and that Mg deficiency (as measured by the Mg loading test) is an important contributing factor.

The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis.

It is evident from several studies that not all patients with hypovitaminosis D develop secondary hyperparathyroidism. What this means for bone biochemistry and bone mineral density (BMD) remains unclear. The aim of this study was to investigate the effects of hypovitaminosis D (defined as a 25OHD < or = 30 nmol/l) and patients with a blunted PTH response (defined arbitrarily as a PTH within the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) in comparison to patients with hypovitaminosis D and secondary hyperparathyroidism (defined arbitrarily as a PTH above the standard laboratory reference range in the presence of a 25OHD < or = 30 nmol/l) and vitamin D-replete subjects (25OHD > 30 nmol/l). Four hundred twenty-one postmenopausal women (mean age: 71.2 years) with established vertebral osteoporosis were evaluated by assessing mean serum calcium, 25OHD, 1,25(OH)2D, bone turnover markers, and BMD. The prevalence of hypovitaminosis D was 39%. Secondary hyperparathyroidism was found in only one-third of these patients who maintained calcium homeostasis at the expense of increased bone turnover relative to the vitamin D-replete subjects (bone ALP mean difference: 43.9 IU/l [95% CI: 24.8, 59.1], osteocalcin: 1.3 ng/ml [95% CI: 1.1, 2.5], free deoxypyridinoline mean difference: 2.6 nmol/nmol creatinine [95% CI: 2.5, 4.8]) and bone loss (total hip BMD mean difference: 0.11 g/cm2 [95% CI: 0.09, 0.12]). Patients with hypovitaminosis D and a blunted PTH response were characterized by a lower serum calcium (mean difference: 0.07 mmol/l [95% CI: 0.08, 0.2]), a reduction in bone turnover (bone ALP mean difference: 42.4 IU/l [95% CI: 27.8, 61.9], osteocalcin: 1.6 ng/ml [95% CI: 0.3, 3.1], free-deoxypyridinoline mean difference: 3.0 nmol/nmol creatinine [95% CI: 1.9, 5.9]), but protection in bone density (total hip BMD mean difference: 0.10 g/cm2, [95% CI: 0.08, 0.11]) as compared to those with hypovitaminosis D and secondary hyperparathyroidism. This study identifies a distinct group of patients with hypovitaminosis D and a blunted PTH response who show a disruption in calcium homeostasis but protected against PTH-mediated bone loss. This has clinical implications with respect to disease definition and may be important in deciding the optimal replacement therapy in patients with hypovitaminosis D but a blunted PTH response.