The effects of acute hyponatraemia on bone turnover in patients with subarachnoid haemorrhage: A preliminary report.

CONTEXT: Animal data and cross-sectional human studies have established that chronic hyponatraemia predisposes to osteoporosis; the effects of acute hyponatraemia on bone turnover have not been determined. Our objective was to test the hypothesis that acute hyponatraemia leads to dynamic effects on bone turnover. DESIGN: A prospective observational pilot study. METHODS: Bone turnover markers [C-terminal crosslinking telopeptide of type 1 collagen (CTX-1), N-propeptide of type 1 collagen (P1NP) and osteocalcin] were measured prospectively over one week in 22 eunatraemic patients with subarachnoid haemorrhage. Patients treated with glucocorticoids were excluded. RESULTS: Eight patients developed acute hyponatraemia, median nadir plasma sodium concentration 131 mmol/L (IQR 128-132), and 14 remained eunatraemic, nadir plasma sodium concentration 136 mmol/L (IQR 133-137). Significant main effects of hyponatraemia were found for P1NP (p = .02) and P1NP:CTX-1 ratio (p = .02), both fell in patients with acute hyponatraemia, with significant interaction between hyponatraemia and time from baseline for P1NP (p = .02). Significant main effects of time from baseline (p < .001) but not hyponatraemia (p = .07) were found for osteocalcin. For CTX-1, significant main effects of time from baseline (p = .001) but not hyponatraemia (p = .65) were found. There was a positive correlation between change in P1NP:CTX-1 ratio and nadir plasma sodium concentration, r = +.43, p = .04. Median serum cortisol (measured on days 1, 3 and 7) was higher in the hyponatraemia group than in those who remained eunatraemic, 545 nmol/L (IQR 373-778) versus 444 nmol/L (IQR 379-542) p = .03. CONCLUSION: These data suggest that acute mild hyponatraemia is associated with a reduction in bone formation activity.

Oxycodone in Palliative Care-Art and Empathy Still Have a Place.

A 47-year-old woman who was receiving palliative care for metastatic breast cancer, which included oxycodone, was found dead in bed. The femoral blood level of oxycodone at autopsy was 1200 µg/L, which is a value within the lethal range. Could the cause of death be attributed to misadventure or suicide? Would the coroner consider a recommendation of therapeutic drug monitoring in palliative care which could have a serious negative impact on pain relief practice? A narrative verdict was the outcome linking the primary cause of death with the drug cocktail found at autopsy.

Should serum calcitonin be routinely measured in patients presenting with thyroid nodule?

BACKGROUND: The European Thyroid Association recommends serum calcitonin measurement in thyroid nodule cases. In contrast, the American Thyroid Association is ambivalent. In this institution, thyroid nodules cases are subject to a multidisciplinary evaluation of the clinical history and examination, ultrasound and scintigraphy, CT scan and sometimes MRI scan, biochemistry and histopathology of biopsies. We report on the current use of plasma calcitonin measurements in the context of changing practice which has not included screening of all thyroid nodules. METHODS: Laboratory records were searched from the beginning of January 2010 to the end of April 2016 for all serum calcitonin measurements. RESULTS: There were 44 patients (30 females, age range 31 to 87 years with median 57.5) and 14 males, age range 20 to 85 years with median 53.4 years) who had a serum calcitonin measured. Of these 33 patients did not have a detectable serum calcitonin. There were 3 patients who had an initial elevated serum calcitonin which became undetectable over time. Over the same time period, a total of 2070 patients presented with thyroid nodules. Medullary thyroid cancer (MTC) was found in 7 cases. Thus assuming all MTC cases had calcitonin measured, MTC is 7 of 341 (2.05%) of the total thyroid cancer burden at the hospital and 7 of 2070 (0.338%) of all thyroid nodules. Our practice is not to routine screen all nodules for MTC. CONCLUSIONS: Because patients with a nodule are subjected to ultrasound scanning and biopsy, when the nodule size is greater than 5 cm or when there is a modifying ultrasound or clinical characteristic, the consensus at the multidisciplinary conference on thyroids rather than universal calcitonin screening of all nodules is the better option in our judgement.

The complexity of PSA interpretation in clinical practice.

Prostate specific antigen (PSA) is central to the diagnosis of prostate cancer. Laboratories quote cut-off reference ranges for PSA but values within these boundaries do not equate with an absence of cancer nor do levels above the range equate with its presence. Convention places the cut-off value at 4 µg/L when calibrated to the Hybritech immunoassay technology and 3.0 or 3.1 µg/L if the PSA methods are calibrated to the WHO IRP 96/670 standard. The prevalence of prostate cancer in screened normal men over 55 years of age with PSA values less than 4 µg/L (Hybritech method) is 10.1% at a PSA of 0.6-1.0 µg/L. About 12.5% of these will be high grade. Two major randomised trials reported on PSA screening. The European trial (ERSPC) reported a risk reduction for prostate cancer death of 21% in the screened group but the US PLCO trial found no benefit. PSA results depend on calibration and there is a 22% difference between the older Hybritech and newer WHO standardisation. Biological variation in PSA is a geometric mean of 7.3%. External quality assessment schemes show wide variation in the performance of PSA analysis. Neither the American College of Physicians nor the UK National Health Service recommends screening except when there is increased risk through family history or ethnicity. Laboratories should detail their method calibration in each report and clinicians should be alerted to the potential misclassification of patients through PSA variation.

Milestones in the evolution of phaeochromocytoma diagnosis.

The history of the discovery of phaeochromocytoma and the original pathological descriptions are described. The clinical history first described in 1886 later led to the realisation that the clinical symptoms and the raised blood pressure were a consequence of catecholamine and the other hormone production by the tumour. The elucidation of its clinical associations with von Hippel Lindau disease neurofibromatosis, multiple endocrine neoplasias and Carney's triad are detailed. Pathologists and scientists are credited with establishing the current biochemical diagnoses. The developments of magnetic resonance imaging and computerised tomography have allowed accurate anatomical localisation. Gene mutations for the clinical syndromes have been identified over the last 14 years. Thus the diagnosis and treatment of this potentially lethal tumour has been made progressively easier.