Hormones and Calcium Metabolism 235 



to understand is the occurrence of osteoporosis in acromegaly and attributed by 

 Albright and Reifenstein (1948) to the effects of secondary adrenocortical over- 

 activity on the synthesis of bone matrix. The hyperphosphataemia is also unexplained. 



The frequency of osteoporosis in acromegaly is uncertain but most workers are 

 agreed that a characteristic feature is hypercalciuria (Bauer and Aub, 1941; Harri- 

 son et ai, 1960; Haymovitz and Horwith, 1964). According to Albright and 

 Reifenstein (1948) this hypercalciuria is the result of the disease whereas Karam 

 et al. (1961) and Haymovitz and Horwith (1964) both suggest that the high 

 urinary calcium contribute to the development of bone disease by causing a negative 

 calcium balance. 



With the advent of purified human growth hormone it has become possible to 

 observe the effects of this hormone in Man and a striking and consistent observation 

 has been the rise in urinary calcium which follows administration of the hormone to 

 cases of hypopituitarism (Ikkos et ai, 1959; Henneman et al., 1960; Fraser and 

 Harrison, 1960). This rise in urinary calcium is associated with a fall in urinary 

 nitrogen and phosphorus. Various workers have tried to establish whether the hyper- 

 calciuria is the result of increased calcium absorption but their results are con- 

 flicting. In three of the four cases reported by Ikkos et al. (1959) the faecal calcium 

 rose whereas in the hypopituitary cases of Henneman et al. (1960) faecal calcium 

 fell, as it did in most of the cases studied by Beck et al. (1960). Moreover, Finkel- 

 STEiN and ScHACHTER (1962) found that growth hormone promoted active calcium 

 transport by the rat duodenum. Fraser and Harrison (1960) confirmed the hyper- 

 calciuric effect of growth hormone in hypophysectomised rats but not in normal rats 

 and showed that the rise in urinary calcium was associated with a corresponding rise 

 in the excretion of Sr^^ with which the skeletons had been labelled. This indicated 

 that the calcium was being withdrawn from the skeleton but since the animals were 

 on a low calcium diet it is difficult to see where else it could have come from. They 

 repeated the observations on rats which had also been parathyroidectomised and 

 found no rise in urinary calcium or strontium. They inferred that the effect of 

 growth hormone on calcium excretion was due to parathyroid stimulation by an 

 overdosage of the hormone. In another paper, Harrison et al. (1960) described a 

 case of acromegaly with hypercalcaemia in which plasma calcium returned to normal 

 after pituitary irradiation. 



Karam et al. (1961) pursued this subject further by postulating that the hyper- 

 calciuria produced by growth hormone might be the result of a fall in the intra- 

 cellular concentration of citrate in the renal tubules. They showed that fluoroacetate 

 given to normal rats raised the urinary and kidney citrate and lowered calcium 

 whereas growth hormone given to hypophysectomised rats lowered renal citrate and 

 raised urinary calcium. The idea that urinary calcium is controlled by renal citrate 

 is a good one but the data are not entirely convincing nor is this concept really 

 compatible with the idea of parathyroid stimulation by the pituitary put forward by 

 the same authors. 



The hyperphosphataemia of acromegaly (Williams, 1964) is well recognised and 

 used by many workers as an indicator of pituitary activity and is reminiscent of the 

 hyperphosphataemia of children. It is associated with an increased Tm phosphate 

 which is said by some, however, only to be increased in proportion to the glomerular 

 filtration rate (Cattaneo et ai, 1964). Since the urinary phosphate is reduced by the 



