The assay of 1alpha,25-dihydroxyvitamin D3: physiologic and pathologic modulation of circulating hormone levels.

A sensitive radioreceptor assay for 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) is utilized to quantitate the circulating concentration of this sterol in experimental animals and humans. When weanling rats are grown for 2 weeks on low calcium or low phosphate diets, limited availability of either ion elicits a five-fold increase in the plasma level of 1alpha,25-(OH)2D3. The enhancement of 1alpha,25-(OH)2D3 in calcium deficiency is dependent upon the presence of the parathyroid and/or thyroid glands, which is consistent with parathyroid hormone (PTH) mediation of this effect. In contrast, the response to phosphate deficiency is independent of these glands and may result from a direct action of low phosphate on the renal synthesis of 1alpha,25-(OH)2D3. Studies in humans indicate that the normal level of 1alpha,25-(OH)2D is 2.1--4.5 ng/100 ml plasma. Patients with chronic renal failure have markedly lower circulating 1alpha,25-(OH)2D and this kidney hormone is undetectable in anephric subjects, but returns to normal within 1 day after successful renal transplantation. Hypoparathyroidism and pseudohypoparathyroidism are associated with reduced plasma 1alpha,25-(OH)2D while patients with primary hyperparathyroidism have significantly elevated sterol hormone levels. Thus, from measurements in rats and humans, it appears that circulating 1alpha,25-(OH)2D3 is regulated by PTH and/or phosphate and that abnormal plasma 1alpha,25-(OH)2D3 is a part of the pathophysiology of renal osteodystrophy and parathyroid disorders.

Vitamin D intoxication in an anephric child.

Although the biologically active metabolite of vitamin D, 1,25-dihydroxycholecalciferol, is synthesized exclusively by kidney tissue, severe hypercalcemia developed in an anephric child treated with large doses of vitamin D. Treatment by calcium-free peritoneal dialysis acutely reduced serum calcium from 17.2 to 14.2 mg/100 ml. This decrement was effected by removal of three times the total calcium in extracellular fluid, suggesting enhanced bone resorption. Oral prednisolone for 7 days reduced serum calcium to 13 mg/100 ml, but hypercalcemia recurred rapidly after prednisolone was stopped. Calcitonin, given for only 4 one-half days, produced normocalcemia. Maximum serum 25-hydroxyvitamin D (25-OHD), observed immediately after vitamin D was stopped, was 635 ng/ml (normal range 23-32 ng/ml) and subsequently decreased with an initial half-time of 10 days. Losses in peritoneal dialysate may have contributed to disappearance of serum 25-OHD. Because of the high serum levels of 25-OHD and absence of renal tissue, 25-OHD was the likely metabolite that caused hypercalcemia, probably by stimulation of bone resorption, though contribution to hypercalcemia by another vitamin D metabolite cannot be absolutely excluded.