Screening for primary aldosteronism using the newly developed IDS-iSYS® automated assay system.

BACKGROUND: The recommended approach to screening for primary aldosteronism (PA) in at-risk populations is to determine the ratio of aldosterone concentration (serum (SAC)/plasma (PAC)) to renin measured in plasma as activity (PRA) or concentration (DRC). However, lack of assay standardisation mandates the need for method-specific decision thresholds and clinical validation in the local population. AIM: The study objective was to establish method-specific aldosterone: renin ratio (ARR) cut-offs for PA in men and women using the IDS-iSYS® assay system (IDS plc). METHODS: A prospective cohort study design was used. PAC and DRC were measured immunochemically in ethylenediamine-tetraacetic acid (EDTA) plasma on the IDS-iSYS® instrument. RESULTS: A total of 437 subjects (218 men, 219 women) were recruited including: healthy normotensive volunteers (n=266) and women taking the oral contraceptive pill (OCP; n=15); patients with essential hypertension (EH; n=128); confirmed PA (n=16); adrenal cortical carcinoma (ACC; n=3); Addison's disease (AD; n=4) and phaeochromocytoma/paraganglioma (PPGL; n=5). In this population, an ARR cut-off at >37.4 pmol/mIU provided 100% diagnostic sensitivity, 96% specificity and positive likelihood ratio for PA of 23:1. When the ARR decision threshold was stratified according to gender, a cut-off of >26.1 pmol/mIU in men and >113.6 pmol/mIU in women resulted in diagnostic sensitivity and specificity of 100%. CONCLUSION: This study demonstrates that decision thresholds for PA should not only be method-specific but also gender-specific. However, given the small number of PA patients (n=16), particularly women (n=4), further validation through a prospective study with a larger PA cohort is required before the thresholds presented here could be recommended for routine clinical use.

Limited utility of tartrate-resistant acid phosphatase isoform 5b in assessing response to therapy in osteoporosis.

BACKGROUND: Tartrate-resistant acid phosphatase isoform 5b (TRACP5b) is a serum bone resorption marker. Our aim was to investigate its utility in monitoring metabolic bone disease. METHODS: Serum TRACP5b, C-terminal cross-linking telopeptide of type I collagen, urine N-terminal cross-linking telopeptide of type I collagen and free deoxypyridinoline were measured pre- and post-treatment with a parathyroid hormone analogue [PTH (1-34)] (n = 14) or a bisphosphonate (N-BP) (n = 8). TRACP5b, bone alkaline phosphatase (bone ALP), 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) were measured in 100 osteoporosis patients on prolonged bisphosphonate therapy. RESULTS: Changes in TRACP5b were smaller in magnitude but mimicked those of other bone resorption markers. Absolute changes in TRACP5b and the other resorption markers correlated significantly (p < 0.001). In patients on long-term bisphosphonates, TRACP5b and bone ALP levels were not suppressed. Vitamin D status was consistent with the level of supplementation. CONCLUSION: TRACP5b has limited utility as a single marker of metabolic bone disease treatment.

A survey of point of care testing in Irish hospitals: room for improvement.

BACKGROUND: "Guidelines for safe and effective management and use of point of care testing" have been recently launched in Ireland. AIMS: To survey point of care testing (POCT) services in the Republic of Ireland. METHODS: A questionnaire covering accreditation status, existence of POCT committees, quality management systems, and staff resources was distributed by the Irish External Quality Assessment Scheme (IEQAS). RESULTS: Of those that returned completed questionnaires, 56% had assigned specific POCT responsibilities to designated staff. Most support was for blood gases and glucose analysis. Compared with other published studies, Irish laboratories gave similar support for blood gases, less for glucose and much less for urinalysis. CONCLUSIONS: This survey demonstrated poor IT support for POCT. The majority of the respondents (78%) were dissatisfied with the quality of the POCT service in their institution.

High bone turnover in Irish professional jockeys.

SUMMARY: Professional jockeys are routinely exposed to high impact trauma and sustain fractures frequently. We found that jockeys restrict their caloric intake in order to maintain regulation weights, and that bone turnover is high. There are significant health and safety implications for the racing industry. INTRODUCTION: Professional jockeys routinely sustain fractures from high impact falls. Jockeys maintain a low percentage body fat and a low body mass index (BMI) to achieve low weight targets in order to race. We evaluated dietary habits and bone metabolism in jockeys. METHODS: Bone mineral density (BMD) was measured in 27 male jockeys of the 144 jockeys licensed in Ireland. Fourteen (52%) had BMD T score below -1.0, of whom 12 consented to clinical review, nutritional survey, endocrine studies, and bone turnover markers (BTM). BTM were compared to age- and sex-matched controls (n = 16). RESULTS: BMI was 20.6 +/- 1.7 kg/m(2); previous fracture frequency was 3.2 +/- 2.0 per rider. All had normal endocrine axes. The jockeys' diet as determined by a 7-day dietary recall was deficient in energy, calcium, and vitamin D intake. Compared with the control group, the jockey group had evidence of increased bone turnover. CONCLUSIONS: A substantial proportion of the professional jockeys in Ireland have low-normal BMD, low BMI, and high bone turnover that may result from weight and dietary restrictions. These factors seem to have a deleterious effect on their bone health and predispose the jockeys to a high fracture risk that should be remediated.

Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda.

Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. Mutations in the uroporphyrinogen decarboxylase gene are present in the low-penetrant, autosomal dominant familial form but not in the commoner sporadic form of porphyria cutanea tarda. We have investigated the relationship between age of onset of skin lesions and mutations (C282Y, H63D) in the hemochromatosis gene in familial (19 patients) and sporadic porphyria cutanea tarda (65 patients). Familial porphyria cutanea tarda was identified by mutational analysis of the uroporphyrinogen decarboxylase gene. Five previously described and eight novel mutations (A80S, R144P, L216Q, E218K, L282R, G303S, 402-403delGT, IVS2 + 2 delTAA) were identified. Homozygosity for the C282Y hemochromatosis mutation was associated with an earlier onset of skin lesions in both familial and sporadic porphyria cutanea tarda, the effect being more marked in familial porphyria cutanea tarda where anticipation was demonstrated in family studies. Analysis of the frequencies of hemochromatosis genotypes in each type of porphyria cutanea tarda indicated that C282Y homozygosity is an important susceptibility factor in both types but suggested that heterozygosity for this mutation has much less effect on the development of the disease.

Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome.

OBJECTIVE: To compare two forms of continuous renal replacement therapy, continuous venovenous hemofiltration (CVVH) vs. continuous venovenous hemodialysis (CVVHD), in terms of the removal of inflammatory mediators from the blood of patients with systemic inflammatory response syndrome and acute renal failure. DESIGN: Randomized crossover, clinical study. SETTING: University teaching hospital. PATIENTS: Thirteen patients with systemic inflammatory response syndrome and acute renal failure receiving continuous renal replacement therapy. INTERVENTION: Patients were randomized to receive either convective clearance using CVVH or diffusive clearance using CVVHD for the first 24 hrs, followed by the other modality for 24 hrs. All treatments utilized AN69 hemofilters. CVVH was performed with an ultrafiltration rate of 2 L/hr and CVVHD with a dialysis outflow rate of 2 L/hr. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and sL-selectin were measured at 0, 1, 3, 6, 12, and 24 hrs by radioimmunoassay. Plasma endotoxin concentrations were also measured at 0, 12, and 24 hrs by chromogenic assay. CVVH was associated with a 13% decrease in plasma TNF-alpha concentrations compared with a 23% increase while on CVVHD (p < .05). Mean plasma concentrations of IL-6, IL-10, and sL-selectin were unchanged over time and between therapies. Only minimal amounts of mediators were recovered in the effluents with either therapy except for IL-6. The clearances for IL-6 were different between therapies, 1.9+/-0.8 (SD) mL/min for CVVHD and 3.3+/-1.5 mL/min for CVVH, (p< .01). Plasma endotoxin concentrations were not different between therapies. CONCLUSION: CVVH resulted in a decrease in plasma TNF-alpha concentrations as compared with CVVHD, while the type of transport mechanism used did not influence plasma concentrations of IL-6, IL-10, soluble L-selectin, or endotoxin. Differences in clearance for IL-6 between CVVH and CVVHD did not translate into significant changes in circulating IL-6 concentrations.