RAREFYING DISEASE OF THE SKELETON 429 



that the adrenal cortex has a dual effect upon calcium metabolism. 

 Excess glucocorticoids induced negative calcium balance, and in- 

 sufficiency caused change in calcium equilibrium characterized by 

 hypercalcemia. The latter was independent of the bone, and the 

 mechanism was different from that produced bv parathyroid hor- 

 mone. Furthermore, this hypercalcemia persisted in parathvroidec- 

 tomized animals, and cortisone in physiologic amounts restored the 

 serum calcium to normal (Kolb and Cohen, 1962). Walser et al. 

 (1962) described 58 samples of the serum of adrenalectomized dogs 

 and attributed the hypercalcemia to a combination of factors, such 

 as hyperproteinemia, due to hemoconcentration; increased affinity 

 of calcium for protein, due to hyponatremia; increased citrate levels, 

 as much as three times normal; and increased amounts of uniden- 

 tified calcium complexes. The effective or free calcium ion concen- 

 tration was not altered bv adrenalectomv. 



Urist ( 1960/? ) reported the case of a 78-year-old woman with 

 severe osteoporosis treated by adrenalectomy. The glands were low 

 in weight, as is usual in persons of advanced age, and there was 

 atrophy of the zona fasciculata of the right, but not of the left, 

 adrenal cortex. Urist and Vincent ( 1960 ) observed that the de- 

 crease in urinary ll-deoxy-17-ketosteroids that occurs in aged 

 women w^as more extreme in women with severe osteoporosis. Cald- 

 well (lQ62b) examined the adrenal glands in 31 autopsy subjects, 

 including 8 cases of senile osteoporosis, and found no evidence of 

 involution or atrophv, and possiblv slightlv greater than normal 

 adrenal cortical cell activitv. These observations suggested that 

 further observations upon the adrenal cortical hormone metabolism 

 in castrates and aged patients with osteoporosis may be of consid- 

 erable value. For some unknown reason, adrenalectomy increased 

 the sensitivity of animals to the side effects of glucocorticoid hor- 

 mones. Both the adrenals and the gonads are markedly diminished 

 in size in birds with osteoporosis (Urist, 1958). Whereas the influ- 

 ence of adrenal hypercorticoidism upon osteoporosis was clearly 

 demonstrable, the effect of endocrine deficiency disorders was quite 

 obscure, and an antiosteoporosis factor produced by the adrenal 

 cortex, the liver, or the skeleton itself, but dependent upon normal 

 endocrine gland function, had to be considered (Urist, 1960b). 



