Excluding familial hypocalciuric hypercalcaemia before surgery for primary hyperparathyroidism - a practical evaluation of urinary calcium using a retrospective cohort design.

INTRODUCTION: Familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism (PHPT) are both associated with raised serum calcium and parathyroid hormone (PTH) levels; the former should be excluded in patients undergoing surgery for the latter. Twenty-four-hour urinary calcium collections (24UCA) can be performed to quantify total calcium excreted; however, results of this method do not take into account factors such as kidney function. Current guidelines suggest measuring urine calcium to creatinine clearance ratio (CCCR) as the initial step. The aim of this study was to evaluate the use of CCCR and 24UCA in a cohort design, to reliably exclude FHH patients before surgery for PHPT. METHODS: A retrospective cohort study of all patients having urine calcium investigations in a single centre, over a 2-year period was performed. Relevant biochemical data and recorded diagnoses were collected. RESULTS: In total, 296 urine calcium measurements were included from 199 patients. Ten (5%) had genetically confirmed or suspected FHH, 171 (85.9%) had surgically proven or suspected PHPT and the remainder had other diagnoses. At a CCCR cut-off of ≤0.020, positive and negative predictive values (PPV and NPV) were 2.33% and 100%, respectively. At a cut-off of ≤0.015, NPV was maintained at 100% and PPV increased to 3.28%. Low 24UCA measurements (<2.5mmol/L/24h) generated a NPV for FHH of 95.2%. CONCLUSION: A CCCR measurement below 0.020 should raise the possibility of FHH and genetic screening should be considered. 24UCA had a lower predictive power to exclude FHH (NPV), and measurements should be interpreted in the context of renal function.

Toxic adenoma: to biopsy or not to biopsy?

Toxic adenoma nodules rarely harbour cancer. Fine-needle aspiration (FNA) is often not done because of the rarity of these lesions being cancer, the difficulty in interpreting cytology in hyperthyroid patients and the rare precipitation of thyrotoxicosis. We present two young, Caucasian female patients aged 29 and 13 years who were each diagnosed with a toxic nodule categorised as benign and indeterminate respectively. They underwent hemithyroidectomy after being rendered euthyroid, however their histology unexpectedly revealed differentiated follicular cancer. Despite thyroid cancer being rare in patients with toxic adenomas, it should be considered when planning treatment, especially if there are risk factors for cancer, or suspicious features on ultrasound examination. A review of the literature shows that compared with adenomas in euthyroid patients, patients in this group are generally younger and predominately female. If an FNA is considered, it should be performed after the patient is rendered euthyroid.

Progress in developing improved programs for pulsed field agarose gel electrophoresis of DNA.

Details are described here for using a rotating gel to perform pulsed field agarose gel electrophoresis (PFGE) with programmable control of the following variables: magnitude of the electrical field, polarity of the electrical field, temperature of the gel and position of the rotating disk upon which the agarose gel rests. By use of this procedure for programmable control, modes of PFGE have been explored that have the following characteristics: (i) resolution by DNA length is completely lost for DNA shorter than a critical length that increases as the pulse times increase, and (ii) resolution by DNA length is enhanced for longer DNAs that are shorter than a second critical length. This window of resolution can be moved to the position of the 2-6 Mb chromosomes of Schizosaccharomyces pombe.