Hypercalcemia etiology

The various etiological theories which have been advanced in respect of idiopathic hypercalcemia are given in Table 2. 

Another possible dietary factor concerns the essential fatty acid content of human and artificial milk. It has been postulated by Sinclair that many modern dietaries are deficient in the essential polyethenoid fatty acids (EFA) and that in consequence there is a rise in unesterified (and more active) vitamin D and in unesterified cholesterol. He has suggested that a part of the etiology of infantile idiopathic hypercalcemia may be attributed to EFA deficiency (S5). He has pointed to the lower content of certain unsaturated fatty acids in cow s milk as compared with human milk as a factor in the development of idiopathic hypercalcemia in artificially fed infants. He considers that dried milk has an even lower content of essential fatty acids than liquid cow s milk and that the longer it is stored the lower does the essential fatty acid content become. On the basis of some observations on rats, he suggests that a dietary deficiency of the essential fatty acids increases susceptibility to the possible toxic effects of vitamin D. The age of the rats, the duration of the essential fatty acid deficient diet, or the dosage of vitamin D is not mentioned, and there would appear to be no other experimental data to support these views. 

Another possible explanation is that in artificial feeding of infants in Britain dried milk powder is predominantly used. In the United States canned evaporated milk is much more popular. Sinclair (S5) states that the essential fatty acid content of dried cow s milk is lower than that of liquid cow s milk and has put this forward as a possible etiological factor. Yet in Britain idiopathic hypercalcemia has occurred in infants who have never received dried milk powder. 

Natural, as opposed to synthetic, vitamin D has its advocates (F9), i.e., vitamin D3 as opposed to vitamin D2. Again there is suggestive evidence that if ingested vitamin D plays any part in the etiology of idiopathic hypercalcemia of infancy, it is vitamin D2 particularly which comes under suspicion. 

Concerning the etiology of idiopathic hypercalcemia, an interesting report has come from Fellers and Schwartz (F3b). By bio-assay methods they estimated the vitamin D-like activity of the serum of two severe cases of idiopathic hypercalcemia and found increased activity. They further found that this increased activity persisted unchanged for periods... 

Common and many of the uncommon etiologies of hypercalcemia are listed in Box 49-2. Primary hyperparathyroidism is the most common cause in outpatients, whereas mahgnancy is the most common cause in hospitalized patients. Together, these two disorders account for 90% to 95% of all cases of hypercalcemia. 

PTH antagonists may also have diagnostic value. Since PTH plays a role in the minute-to-minute regulation of blood calcium levels, short-term administration of a PTH antagonist may cause a rapid reduction in blood calcium levels in hypercalcemic patients if the hypercalcemia is due to elevated PTH levels. Similarly, short-term amelioration of possible symptoms of hypercalcemia (such as lethargy, cognitive defects) may help pinpoint the etiology of the symptoms (i.e. hyperparathyroidism vs. other disorders). 

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