Hormones and Calcium Metabolism 227 



requirement of protein and vitamins. This brought thyrotoxic bone disease into line 

 with their protein matrix hypothesis for osteoporosis. 



This concept that thyrotoxic osteoporosis was connected in some way with the 

 negative nitrogen balance which is a feature of hyperthyroidism was accepted (per- 

 haps rather uncritically) until Krane et al. (1956), showing that the calcium balance 

 might be negative even when the nitrogen balance was positive, challenged it. Cook 

 et al. (1959) also failed to find any correlation between calcium and nitrogen balance 

 in hyperthyroidism and Puppel et al. (1945) had previously shown that oral 

 administration of calcium alone could produce a positive calcium balance in patients 

 with hyperthyroidism. 



The protein matrix concept had previously been questioned at the histological 

 level. As early as 1933 Askanazy and Rutishauser had shown that the histology of 

 thyrotoxic bone disease resembled that of osteitis fibrosa, and this was subsequently 

 confirmed by Follis (1953) in a paper which has become a classic. These observations 

 showed that the osteoporosis was probably caused by increased bone destruction 

 rather than diminished formation. 



The present view is undoubtedly that the effect of hyperthyroidism on calcium 

 metabolism is to increase rather than decrease the rates of bone formation and 

 destruction. Krane et al. (1956) were the first to use radiocalcium to demonstrate 

 accelerated bone turnover in thyrotoxicosis, and this observation was subsequently 

 confirmed by Fraser et al. (1960) with stable strontium. The in vitro uptake of 

 radiophosphorus by bone powder has been shown by Hernberg (1960) to be in- 

 creased in thyrotoxicosis and this again is taken to signify an increased rate of new 

 bone formation. The enhancing effect of thyroid hormone on bone resorption has 

 been demonstrated by the elevation of urinary hydroxyproline in thyrotoxicosis 

 which has been reported by Kirivikko et al. (1964) and Benoit et al. (1963). 

 Conversely Heaney and Whedon (1958) have shown the bone formation rate to be 

 lowe in myxoedema. 



It has already been mentioned that early calcium balance studies in thyrotoxicosis 

 showed both the faecal and urinary calcium to be increased. This was amply con- 

 firmed by Cook et al. (1959) in calcium balances on nine cases. In four of these the 

 urinary calcium exceeded 900 mg. daily and in four the faecal calcium exceeded the 

 dietary intake. This latter observation suggests an increase in the endogenous faecal 

 or digestive juice calcium, but this is not born out by examination of the data of 

 Krane et al. (1956). Cook et al. (1959) also found an increased faecal fat in eight 

 of their nine patients, possibly due to intestinal hurry. 



Fiypercalcluria was also a feature of the hyperthyroid cases described by Green 

 and Lyall (1951) and this hypercalciuria was supressed in the one patient to whom 

 they administered alkali. This latter observation is one which we have since confirmed 

 and we have also found (as have Hernberg and Jakobsen, 1964) that the urinary 

 calcium in thyrotoxicosis is a function of the severity of the disease. In our experience, 

 it is correlated with the plasma level of protein bound iodine (Nordin, 1964) (Fig. 1). 



The plasma calcium also tends to rise in hyperthyroidism (Harrison et al., 1964) 

 and a number of cases of frank hypercalcaemia have been reported (Rose and Boles, 

 1953; Pribek and Meade, 1957; Kleeman et al, 1958; Guyer, 1965). In one case 

 (Sataline et al., 1962) this hypercalcaemia was reversed by cortisone but in another 

 (David et al., 1962) it was not. 



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