The effects on dogs of large doses of calciferol (vitamin D)

Abstract

A number of investigations have appeared to show some relation between the rise of blood calcium produced by excessive doses of vitamin D and the action of the parathyroid glands. Jones (1926) had shown that the administration of cod liver oil to dogs in large doses, for some weeks before removal of the parathyroids, prevented the usual onset of tetany and increased the length of survival, whereas similar treatment with the oil was ineffective after the glands had been removed. The result in line with a suggestion which had already been made with reference to irradiation [Block and Faber (1925)] that the effects of excessive does of the vitamin D on blood calcium were not produced by a direct action, but by stimulation of excessive output of the parathyroid hormone. Greenwald and Gross (1929) explained Jones’ results in this way, and showed that even 300-400 mgm. of irradiated ergosterol did not definitely relieve tetany or raise the blood calcium, unless it was supplemented by adding calcium to the diet. The experiments of Hess and his co-workers [Hess and Lewis (1928); Hess, Weinstock and Rivkin (1929, 1930); Hess, Benjamin and Gross (1931)] seemed to point, on the whole, in the same direction. Their results showed that larger doses of irradiated ergosterol are needed to produce a rise of blood-calcium on a calcium-free than on normal diets, and that still larger doses are necessary if the parathyroids have been removed in addition. These and other similar investigations appeared to show that the effects of vitamin D, when given is does large enough to cause a toxic hypercalcæmia, may be produced in several ways: (1) when there is plenty of calcium in the food, large doses of the vitamin promote excessive absorption of calcium from the alimentary canal, or alternatively, diminished re-excretion into the bowel [Taylor and Weld (1932)], just as therapeutic doses bring back a defective absorption to within the normal range. (2) When calcium is deficient in or absent from the food, larger doses of the vitamin can still cause a hypercalcæmia by withdrawal of calcium from the tissues. The work of Kreitmair and Hintzelmann (1928), Baumgartner, King and Page (1929), György (1930), Harris and Innes (1931), and Shelling (1932, 2) has shown that under such conditions calcium is withdrawn from the bones. (3) When the parathyroids are removed from an animal on a calcium-free diet, very large does of the vitamin can still produce hypercalcæmia [Jones, Rapoport and Hodes (1930); Shelling (1932, 1)].