Familial benign hypercalcemia (FBH) and neonatal hyperparathyroidism (NHPT) are disorders of calcium homeostasis that are associated with missense mutations of the calcium-sensing receptor (CaR). We have undertaken studies to characterize such CaR mutations in FBH and NHPT and to explore methods for their more rapid detection. Nine unrelated kindreds (39 affected, 32 unaffected members) with FBH and three unrelated children with sporadic NHPT were investigated for mutations in the 3,234-bp coding region of the CaR gene by DNA sequencing. Six novel heterozygous (one nonsense and five missense) mutations were identified in six of the nine FBH kindreds, and two de novo heterozygous missense mutations and one homozygous frame-shift mutation were identified in the three children with NHPT. Our results expand the phenotypes associated with CaR mutations to include sporadic NHPT. Singlestranded conformational polymorphism analysis was found to be a sensitive and specific mutational screening method that detected > 85% of these CaR gene mutations. The single-stranded conformational polymorphism identification of CaR mutations may help in the distinction of FBH from mild primary hyperparathyroidism which can be clinically difficult. Thus, the results of our study will help to supplement the clinical evaluation of some hypercalcemic patients and to elucidate further the structure-function relation-

Forty-eight patients treated with oral lithium carbonate and 20 control subjects were studied to define the causes of lithium-induced water disturbances. Measurement of plasma immunoreactive arginine vasopressin, plasma osmolality, and urine osmolality after a period of dehydration separated nephrogenic diabetes insipidus, cranial diabetes insipidus, and primary polydipsia, the three postulated mechanisms of lithium-induced polyuria. Seventeen patients had a urinary concentrating defect despite serum lithium concentrations in the therapeutic range. Ten of these patients had nephrogenic diabetes insipidus, one had results suggestive of cranial diabetes insipidus, but none had evidence of primary polydipsia. Symptoms of thirst and polyuria were poor indicators of the degree of hypo-osmolar urine. No patient had electrolyte abnormalities, and none had sufficiently severe polyuria to stop lithium treatment.

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A dual-energy X-ray absorptiometry (DXA) machine was used to measure the bone mineral density (BMD) of both femora in 760 female volunteers. Each volunteer completed a questionnaire and exclusion criteria were applied such that only 480 of these were considered normal subjects. The remaining 280 women failed to comply with the criteria and were considered 'abnormal'; their BMD results were analysed separately. Two abnormal subgroups, one with previous long bone fractures and one with radiologically diagnosed osteopenia, were studied. BMD values for femoral neck, Ward's triangle and trochanter were compared between the two femora in all the above groups. No dominance relationship was found when comparing left to right femur, averaged over any population studied, but large differences were found between the femora in individual volunteers. There was a high correlation between BMD in opposing femora of 0.91, 0.91 and 0.84 for the femoral neck, Ward's triangle and trochanter respectively. However, in normal subjects the percentage variation in these regions ranged up to 34%, 64% and 80% respectively at the different femoral sites. In addition, the normal population was divided into two subgroups, one in which the density difference between the femora was large, and the other in which the difference was statistically insignificant. The analytical and anatomical variations between these two groups were investigated. Only part of the difference appeared to be due to analytical problems and it seems that there is a genuine difference in femoral density. Poor correlation for femoral neck percentage density difference was found with average BMD, age, height and weight in the normal population.(ABSTRACT TRUNCATED AT 250 WORDS)