Mary D. Gardner

COMPARISON OF AMINOHYDROXYPROPYLIDENE DIPHOSPHONATE, MITHRAMYCIN, AND CORTICOSTEROIDSICALCITONIN IN TREATMENT OF CANCER-ASSOCIATED HYPERCALCAEMIA

Thirty-nine patients with cancer-associated hypercalcaemia were randomly allocated to receive aminohydroxypropylidene diphosphonate (APD), mithramycin, or corticosteroids and salmon calcitonin. Corticosteroids/calcitonin had the fastest calcium-lowering effect, owing mainly to an acute reduction in renal tubular calcium reabsorption; continued therapy over 9 days failed to suppress accelerated bone resorption, however, and most patients remained hypercalcaemic. Mithramycin also substantially reduced serum calcium within 24 h. A further dose on day 2 generally controlled hypercalcaemia until day 6 by reducing both bone resorption and renal tubular calcium reabsorption. By day 9, however, about 50% of the mithramycin-treated patients had started to relapse as bone resorption increased again. With APD serum calcium levels fell more slowly but progressively owing to effective suppression of bone resorption; by day 9 the control of hypercalcaemia was significantly better than in the other treatment groups. Symptoms of hypercalcaemia were greatly relieved, especially by APD.

Late rickets and osteomalacia in the Pakistani community in Glasgow.

T HIS paper reports the results of a survey carried out in May 1961 to discover how common late rickets and osteomalacia are among Pakistanis living in Glasgow. The survey was made following the discovery of active rickets in a Pakistani girl of 14 years and the subsequent finding of late rickets in her sister, aged 13 years, and brother, aged 17 years. The mother of these children was found at the same time to be suffering from osteomalacia. The results of the investigation show that late rickets and mild osteomalacia are common in the Pakistani community in Glasgow. The environmental and dietary factors which have produced this vitamin D deficiency are discussed in the light of a preliminary inquiry into the dietary habits and social conditions of the families involved.

Predictive Value of Derived Calcium Figures Based on the Measurement of Ionised Calcium

The algorithms used in this hospital to assess calcium status are calculated ionised serum calcium and the serum calcium concentration adjusted for albumin. In order to establish their clinical usefulness, they were compared with the ionised calcium concentration measured on the Nova 2 instrument in patients with various calcium and protein abnormalities. Good correlation was found between the measured and calculated values. The predictive values for the calculated results and for total serum calcium concentrations are presented. In this series, the derived values were useful in predicting the serum ionised calcium concentration of the patients studied.

Hypercalcaemia and metastatic bone disease: is there a causal link?

The relation between serum calcium and the extent of metastatic bone disease as judged by radionuclide bone scan was examined in a consecutive series of 195 patients with malignant disease. Of 87 patients with hypercalcaemia, 40% had no evidence of skeletal metastatic bone disease and serum calcium values. Of 160 patients judged to have bone-scan evidence of metastatic skeletal involvement, only 32.5% were significantly hypercalcaemic. Further, a negative correlation was found between the extent of metastatic bone disease and serum calcium value. The development of hypercalcaemia in malignancy is not directly related to the presence or extent of metastatic bone disease. It is suggested that the development of hypercalcaemia may depend on an alternative mechanism, such as the production of a humoral substance by tumour tissue, having its effect on calcium metabolism at sites or organs distant from local areas of tumor involvement.

COMPARISON OF INTESTINAL CALCIUM ABSORPTION AND CIRCULATING 1,25‐DIHYDROXYVITAMIN D LEVELS IN MALIGNANCY‐ASSOCIATED HYPERCALCAEMIA AND PRIMARY HYPERPARATHYROIDISM

The relation between circulating 1,25‐dihydroxyvitamin D (l,25(OH)2D) levels and intestinal calcium absorption–as determined by an oral calcium load test–was studied in 16 patients with hypercalcaemia of malignancy (HM) and 16 with hypercalcaemic primary parathyroidism (HPT). In the HPT group serum calcium rose significantly after the oral calcium load and the increment correlated significantly with 1,25(OH)2D levels. While 1,25(OH)2D levels were raised to within the hyperparathyroid range in a number of HM patients, there was no correlation between change in serum calcium and 1,25(OH)2D level in the HM group and serum calcium did not rise significantly after the oral calcium load. HM patients with detectable or raised 1,25(OH)2D levels typically had few, or no, bone metastases in association with squamous lung cancers. A high proportion of these patients exhibited other aspects of hyperparathyroid‐like activity such as increased renal tubular calcium reabsorption, depressed renal tubular phosphate reabsorption and elevated urinary cyclic AMP excretion. Conversely, HM patients with undetectable 1,25(OH)2D levels typically had extensive metastatic bone disease in association with breast carcinoma and were less likely to exhibit other hyperparathyroid‐like features. It is postulated that in the former, the ‘inappropriately’ detectable or raised 1,25(OH)2D levels may have been due to enhanced renal la‐hydroxylase activity stimulated by the parathyroid hormone (PTH)‐like effect of a non‐PTH ectopic humoral mediator. In the latter the suppressed 1,25(OH)2D levels would be the predicted result of a non humorally mediated hypercalcaemia. It is currently unclear why intestinal calcium absorption was depressed in all HM patients when 1,25(OH)2D levels were normal or raised in some cases. It is possible, however, that in HM there is ‘end organ’ resistance to the effects of 1,25(OH)zD due to a generalized malabsorptive process.

Pre-operative localisation of parathyroid tumours using neck vein catheterisation and radioimmunoassay for parathyroid hormone: the Glasgow experience.

Reliable pre-operative localisation of parathyroid tumours can be of value in surgery for primary hyperparathyroidism, and particularly so where re-exploration of the neck is required. Neck vein catheterisation and parathyroid hormone radioimmunoassay have been suggested as a sensitive means of tumour localisation, and we report our experience of the technique over the last five years. A total of 46 patients with primary hyperparathyroidism had 50 studies performed with positive localisation and a pre-operative prediction made on 38 occasions (76%). Forty-two operations were carried out and a parathyroid tumour confirmed in 39 cases for a localisation efficiency of 69 per cent. No negative neck exploration followed a positive localisation. Twelve studies were performed in patients with renal osteodystrophy and localisation to a single site was achieved on only three occasions. It is concluded that neck vein catheterisation and parathyroid hormone assay can correctly localise parathyroid tumours in most cases of primary hyperparathyroidism, but is is suggested that its use be restricted to selected cases such as those subjects with previous negative neck exploration or patients for whom prolonged or repeated surgery may be a particular hazard.

Preparation of material to control precision of calcium selective electrodes

A simple procedure is described for the preparation of a stable precision quality control material for use in the measurement of levels of ionised calcium in serum at or near the reference range. Repeat analyses on a Nova 2 ionised calcium analyser of serum pools stored at different temperatures over a period of three months showed coefficients of variation of less than 4%.

Further electrode evaluation of the Nova 2 ionised calcium instrument

Introduction In the original evaluation of the Nova 2 analyser [1] inter-electrode differences were shown which would have necessitated the re-establishment of the ionised calcium reference range each time that the calcium ion-selective electrode was changed. The manufacturers (Nova Biomedical, Newtown, Mass, USA) have now replaced the electrodes which showed slow and variable response times to serum, and it has been possible to compare these two replacement electrodes with the original electrode (still in service after 14 months). Another electrode, replaced under warranty, and two supplied with a second instrument on loan from the British Agents (American Hospital Supplies,.Didcot, Oxon, UK) were also compared with the original electrode. In all a total of six electrodes were evaluated.