Vitamin D insufficiency and deficiency have been associated with an increased risk of adverse pregnancy outcomes. Controversy remains as findings have been inconsistent between disparate populations. The aim of this study was to investigate the relationship between vitamin D status and pregnancy outcomes in a large, prospective pregnancy cohort. 25-Hydroxyvitamin D concentration was analysed in serum samples collected at 15 weeks of gestation from 1710 New Zealand women participating in a large, observational study. Associations between vitamin D status and pre-eclampsia, preterm birth, small for gestational age (SGA) and gestational diabetes were investigated. The mean 25-hydroxyvitamin D concentration was 72·9 nmol/l. In all, 23 % had 25-hydroxyvitamin D concentrations <50 nmol/l, and 5 % of participants had concentrations <25 nmol/l. Women with 25-hydroxyvitamin D concentrations 75 nmol/l (OR 2·3; 95 % CI 1·1, 5·1). However, this effect was not significant when adjustments were made for BMI and ethnicity (OR 1·8; 95 % CI 0·8, 4·2). 25-Hydroxyvitamin D concentration at 15 weeks was not associated with development of pre-eclampsia, spontaneous preterm birth or SGA infants. Pregnancy complications were low in this largely vitamin D-replete population.
Gas Chromatography-Mass Spectrometry (GC-MS) has long been used for metabolite profiling of a wide range of biological samples. Many derivatisation protocols are already available and among these, trimethylsilyl (TMS) derivatisation is one of the most widely used in metabolomics. However, most TMS methods rely on off-line derivatisation prior to GC-MS analysis. In the case of manual off-line TMS derivatisation, the derivative created is unstable, so reduction in recoveries occurs over time. Thus, derivatisation is carried out in small batches. Here, we present a fully automated TMS derivatisation protocol using robotic autosamplers and we also evaluate a commercial software, Maestro available from Gerstel GmbH. Because of automation, there was no waiting time of derivatised samples on the autosamplers, thus reducing degradation of unstable metabolites. Moreover, this method allowed us to overlap samples and improved throughputs. We compared data obtained from both manual and automated TMS methods performed on three different matrices, including standard mix, wine, and plasma samples. The automated TMS method showed better reproducibility and higher peak intensity for most of the identified metabolites than the manual derivatisation method. We also validated the automated method using 114 quality control plasma samples. Additionally, we showed that this online method was highly reproducible for most of the metabolites detected and identified (RSD < 20) and specifically achieved excellent results for sugars, sugar alcohols, and some organic acids. To the very best of our knowledge, this is the first time that the automated TMS method has been applied to analyse a large number of complex plasma samples. Furthermore, we found that this method was highly applicable for routine metabolite profiling (both targeted and untargeted) in any metabolomics laboratory.
Introduction: Cushing’s syndrome (CS) due to ectopic adrenocorticotrophic hormone (ACTH) is rare and usually due to neuroendocrine neoplasia (NEN). Primary renal NEN is exceptionally rare but may be a cause of rapidly progressive CS. Case Presentation: A 51-year-old man presented with profound hypokalemia, cellulitis, and new-onset type 2 diabetes and hypertension with 1 month of muscle weakness, labile mood, and insomnia. CS due to ectopic ACTH production was confirmed. Biochemical control was achieved using a “block-and-replace” regimen with dual blockade with ketoconazole and metyrapone and hydrocortisone replacement in addition to mineralocorticoid receptor blockade using spironolactone. CT and ultrasound demonstrated a 24 mm right renal lesion with features concerning for renal cell carcinoma. Right laparoscopic nephrectomy was performed. Histology demonstrated a WHO grade one NEN with ACTH staining. Conclusion: In CS, where the source of ectopic ACTH production is unable to be identified, a renal source should be considered. Diagnosis may be difficult as there are no reliable radiological characteristics to distinguish renal NENs from renal cell carcinomas, so a high degree of suspicion is required.
Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by FGF23-secreting tumours. Although typically benign, TIO may result in severe pain and disability. Surgical resection has been the traditional management however, due to tumour location, even some small lesions may require major surgery. Radiofrequency ablation (RFA) provides an alternative to surgery and offers the potential for cure of lesions not easily amenable to surgical resection. We describe the short- and long-term outcomes of three patients following RFA. CT-guided RFA has the potential to cure TIO and should be considered appropriate first-line management for suitable lesions.