Robert A. Cowan

An Evaluation of Bone Density and Turnover in Premenopausal Women with Type 1 Diabetes Mellitus

Measurement of bone density and turnover was assessed in 20 premenopausal females with Type 1 diabetes mellitus and 27 age‐sex‐matched controls. Measurement was made of spinal (L2–4) and neck of femur bone density by dual‐energy X‐ray absorptiometry. L2–4 density was significantly higher in the diabetic patients compared with controls (1.224 ± 0.021 g cm−2 vs 1.161 ± 0.020 g cm−2: p = 0.016). No significant difference was noted between the groups in neck of femur density. Measurement of bone formation was assessed by serum alkaline phosphatase and bone resorption by fasting urinary hydroxyproline/creatinine ratio. Alkaline phosphatase was significantly higher in the diabetic patients (185 ± 16 U l−1 vs 135 ± 10 U l−1: p < 0.01) as was hydroxyproline/creatinine ratio (0.028 ± 0.003 vs 0.017 ± 0.002: p = 0.002). No significant correlation was found between L2–4 density and glycated haemoglobin, duration of diabetes or daily dose of insulin taken. These data suggest that osteopenia is not associated with Type 1 diabetes mellitus; however these patients do have evidence of increased bone turnover and may therefore be at risk of osteoporosis in later life, particularly after the menopause.

Hormone Binding Globulins and Anticonvulsant Therapy

Serum sex hormone binding globulin, thyroxine binding globulin, cortisol binding globulin and vitamin D binding globulin, together with total levels of the appropriate bound hormones, were determined in 21 epileptic subjects who had been stabilised by long-term anticonvulsant therapy. Serum sex hormone binding globulin capacity was higher in these patients than in appropriate control groups (men p<0.05; women p<0.01), and values correlated with serum phenytoin levels in the female subjects (p<0.01). Thyroxine binding globulin levels were unaffected by anticonvulsants, but significant reductions in serum thyroxine (men p<0.05; women p<0.001) and triiodothyronine (men p<0.05; women p<0.01) were observed. Cortisol binding globulin capacity was appreciably elevated in patients of either sex (p<0.001), and in the women this was accompanied by a reduction in serum cortisol (p<0.001) and a significant correlation with the serum phenytoin concentration (p<0.01). Neither vitamin D binding globulin capacity nor serum 25-hydroxycholecalciferol levels were influenced by anticonvulsants in this study. It is concluded that anticonvulsant drug therapy causes widespread alterations in the normal homeostasis between hormones and their serum binding globulins. Such alterations may well have clinical significance.

A comparison of low versus high dose pamidronate in cancer-associated hypercalcaemia

Pamidronate has been demonstrated to be an effective agent in the treatment of cancer-associated hypercalcaemia. The dose regime, however, remains controversial. In this study 16 patients with cancer-associated hypercalcaemia were given 30 mg pamidronate by intravenous infusion and 16 were given 90 mg also by infusion. Groups were well-matched in terms of tumour types, bone metastases, pre-treatment serum calcium and creatinine, fasting urinary calcium/creatinine ratio, nephrogenous cAMP and the renal tubular threshold for phosphate reabsorption (TmPO4). The calcium lowering effect was similar in both treatment groups with nadir at day 6 of mean (+/- SEM) 2.48 mmol/l (+/- 0.06) in the 30 mg group and at day 9 in the 90 mg group of 2.51 mmol/l (+/- 0.03) (P less than 0.01). 10 patients in the 30 mg group and 8 in the 90 mg group were normocalcaemic at this point. Similarly when those patients with more severe hypercalcaemia (greater than 3.30 mmol/l, n = 7 in each group) were analysed separately, no significant difference was evident between the two groups. Urinary calcium/creatinine ratios fell to a nadir at day 6 in both groups of 0.33 (+/- 0.05) (30 mg group) and 0.37 (+/- 0.10) (90 mg group) (P less than 0.01). Follow-up results after the initial 9 days showed the mean time to relapse to be 38 days (range 18-90) in the 30 mg group and 34 days (11-105) in the 90 mg group.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy.

SummaryIn this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n=13), 45 mg (n=9), and 90 mg (n=13) in an attempt to see what factors influenced the response of serum calcium to pamidronate.The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into “good” and “poor” responders depending on whether a normal serum calcium was obtained.Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r=0.45, P=0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean±SEM): 65.0±9.4 nmol/liter GF (poor responders) versus 29.6±6.3 (good responders), P=0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r=-0.41, P=0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF±0.09 (poor responders) versus 0.76 mmol/liter GF±0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response. A significant negative correlation was evident between NcAMP and TmPO4 (r=-0.35, P=0.003), however, no significant correlation was evident between NcAMP and TmCa or TmPO4 and TmCa.These results suggest that in a hypercalcemic patient where evidence exists for the presence in circulation of a factor with PTH-like activity (i.e., NcAMP is elevated or TmPO4 is low) the response of serum calcium to pamidronate is less good. NcAMP would appear to be a useful predictor of the response of serum calcium, whereas TmPO4 is less discriminating.

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.