Hormones and Calcium Metabolism 233 



found that hypocalcaemia following parathyroidectomy was aggravated by hydro- 

 cortisone and that the amount of parathyroid extract required to maintain serum 

 calcium concentration was increased in the presence of hydrocortisone. 



In man hypophosphataemia with a raised phosphate clearance is sometimes seen 

 in Cushing's syndrome and could be due to secondary hyperparathyroidism (Nordin 

 and Fraser, 1960). The hypocalcaemic effect of cortisone is well established in 

 sarcoidosis and it has also been reported in vitamin D intoxication (Verner et ai, 

 1958) in thyrotoxicosis (Sataline et al., 1962) and in multiple myeloma (Merigan 

 and Hayes, 1961). Cortisone responsive hypercalcaemia has also been reported 

 occasionally in proven hyperparathyroidism (Gwinup and Sayle, 1961). This hypo- 

 calcaemic action is not confined to cortisone itself since it has frequently been 

 reported with prednisone as well (Bentzel et al., 1964). 



The mode of action of the corticosteroids on plasma calcium is quite uncertain 

 but they have at times been thought to be antagonistic to parathyroid hormone 

 (Laron et ai, 1958; Myers, 1962) and at other times to antagonise the action of 

 vitamin D (Anderson et ai, 1954; Scholz, 1959). As far as the former concept is 

 concerned, the apparently hypocalcaemic action of corticosteroids in parathyroid- 

 ectomised animals (Stoerk et ai, 1963) tends to rule it out. As far as the second 

 concept — antagonism to vitamin D — is concerned, the circumstances in which this 

 antagonism operates appear to be quite limited. Thus Harrison and Harrison 

 (1958) found that Cortisol did not prevent the healing of rickets in rachitic rats given 

 vitamin D, and Thomas and Morgan (1958) found that it did not prevent the 

 development of hypercalcaemia in rats given large doses of vitamin D. 



Jackson and Dancaster (1963) investigated this subject in four male adult 

 volunteers in whom they failed to prevent the development of vitamin D poisoning 

 by the simultaneous administration of large doses of cortisone and vitamin D. More- 

 over, patients with adrenal insufficiency were no more sensitive to calciferol than 

 those with hyperadrenocortisism. 



A hypocalcaemic effect of corticosteroids is again apparent in the hypercalcaemia 

 of adrenal insufficiency (Sprague et ai, 1956; Leeksma et al., 1957). The nature of 

 this hypercalcaemia has been carefully investigated by Robinson and "Walser (1964) 

 and Myers et al. (1964). Both these groups measured calcium fractions in the plasma 

 of normal and adrenalectomised dogs and found that the hypercalcaemia following 

 Cortisol withdrawal could be explained by the following processes: 



1. Dehydration and consequent increased protein concentration. 



2. Increased calcium-binding by the proteins. 



3. Increased ultrafiltrable calcium due both to increased calcium citrate and in- 

 crease in other complexes. 



Both groups agreed that the ionic calcium remains normal. These observations are 

 difficult to reconcile with the clinical picture of nausea and vomiting following 

 adrenalectomy described by Sprague et al. (1956) which suggests a raised ionic 

 calcium in the blood. The implication that the corticosteroids do not affect ionic 

 calcium concentrations is also difficult to reconcile with their hypocalcaemic action 

 in vitamin D poisoning, hypercalcaemia of malignant disease and other conditions. 

 It is hard to believe that cortisone reduces plasma calcium in these diseases without 

 modifying the ionic fraction. 



