Abstract
Mean plasma 1α,25-dihydroxyvitamin D[1α,25(OH)2D] was significantly increased and serum parathyroid hormone was suppressed in three patients with sarcoidosis and hypercalcemia. Prednisone lowered the mean plasma 1α,25(OH)2D to normal range and corrected the hypercalcemia. To elucidate the mechanism for the increased sensitivity to vitamin D in this disorder, the effects of orally-administered vitamin D2 were determined in seven normal subjects, four patients with sarcoidosis and normal calcium metabolism and three patients with sarcoidosis and a history of hypercalcemia who were normocalcemic when studied. Serum and urinary calcium, serum 25-hydroxyvitamin D (25-OHD), plasma 1α,25(OH)2D and, in some studies, calcium balance were measured. Vitamin D2, 250 μg a day for 12 d, produced little, if any, change in mean plasma 1α,25(OH)2D and in urinary calcium in the normals and in the patients with normal calcium metabolism. In contrast, vitamin D2 produced increases in plasma 1α,25(OH)2D from concentrations which were within the normal range (20-55 pg/ml) to abnormal values and increased urinary calcium in two patients with abnormal calcium metabolism. In an abbreviated study in the third patient, vitamin D2, 250 μg a day for 4 d, also increased plasma 1α,25(OH)2D abnormally from a normal value. There was a highly significant correlation between plasma 1α,25(OH)2D and urinary calcium. Serum 25-OHD and serum calcium remained within the normal range in all subjects and patients. These findings provide evidence that the defect in calcium metabolism in sarcoidosis probably results from impaired regulation of the production and(or) degradation of 1α,25(OH)2D. Prednisone may act to correct the abnormal calcium metabolism by reducing circulating 1α,25(OH)2D.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ALBRIGHT F., CARROLL E. L., DEMPSEY E. F., HENNEMAN P. H. The cause of hypercalcuria in sarcoid and its treatment with cortisone and sodium phytate. J Clin Invest. 1956 Nov;35(11):1229–1242. doi: 10.1172/JCI103378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ANDERSON J., HARPER C., DENT C. E., PHILPOT G. R. Effect of cortisone on calcium metabolism in sarcoidosis with hypercalcaemia; possibly antagonistic actions of cortisone and vitamin D. Lancet. 1954 Oct 9;267(6841):720–724. doi: 10.1016/s0140-6736(54)90492-4. [DOI] [PubMed] [Google Scholar]
- BELL N. H., BARTTER F. C. TRANSIENT REVERSAL OF HYPERABSORPTION OF CALCIUM AND OF ABNORMAL SENSITIVITY TO VITAMIN D IN A PATIENT WITH SARCOIDOSIS DURING EPISODE OF NEPHRITIS. Ann Intern Med. 1964 Oct;61:702–710. doi: 10.7326/0003-4819-61-4-702. [DOI] [PubMed] [Google Scholar]
- BELL N. H., GILL J. R., Jr, BARTTER F. C. ON THE ABNORMAL CALCIUM ABSORPTION IN SARCOIDOSIS. EVIDENCE FOR INCREASED SENSITIVITY TO VITAMIN D. Am J Med. 1964 Apr;36:500–513. doi: 10.1016/0002-9343(64)90099-3. [DOI] [PubMed] [Google Scholar]
- Bell N. H., Bartter F. C. Studies of 47-Ca metabolism in sarcoidosis: evidence for increased sensitivity of bone to vitamin D. Acta Endocrinol (Copenh) 1967 Jan;54(1):173–180. doi: 10.1530/acta.0.0540173. [DOI] [PubMed] [Google Scholar]
- Belsey R. E., DeLuca H. F., Potts J. T., Jr A rapid assay for 25-OH-vitamin D3 without preparative chromatography. J Clin Endocrinol Metab. 1974 Jun;38(6):1046–1051. doi: 10.1210/jcem-38-6-1046. [DOI] [PubMed] [Google Scholar]
- Carré M., Ayigbedé O., Miravet L., Rasmussen H. The effect of Prednisolone upon the metabolism and action of 25-hydroxy-and 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1974 Aug;71(8):2996–3000. doi: 10.1073/pnas.71.8.2996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chesney R. W., Mazess R. B., Hamstra A. J., DeLuca H. F., O'Reagan S. Reduction of serum-1, 25-dihydroxyvitamin-D3 in children receiving glucocorticoids. Lancet. 1978 Nov 25;2(8100):1123–1125. doi: 10.1016/s0140-6736(78)92277-8. [DOI] [PubMed] [Google Scholar]
- Connerty H. V., Briggs A. R. Determination of serum calcium by means of orthocresolphthalein complexone. Am J Clin Pathol. 1966 Mar;45(3):290–296. doi: 10.1093/ajcp/45.3.290. [DOI] [PubMed] [Google Scholar]
- Cushard W. G., Jr, Simon A. B., Canterbury J. M., Reiss E. Parathyroid function in sarcoidosis. N Engl J Med. 1972 Feb 24;286(8):395–398. doi: 10.1056/NEJM197202242860803. [DOI] [PubMed] [Google Scholar]
- Disanto A. R., Desante K. A. Bioavailability and pharmacokinetics of prednisone in humans. J Pharm Sci. 1975 Jan;64(1):109–112. doi: 10.1002/jps.2600640122. [DOI] [PubMed] [Google Scholar]
- Dorantes L. M., Arnaud S. B., Arnaud C. D. Importance of the isolation of 25-hydroxyvitamin D before assay. J Lab Clin Med. 1978 May;91(5):791–796. [PubMed] [Google Scholar]
- Eisman J. A., Hamstra A. J., Kream B. E., DeLuca H. F. A sensitive, precise, and convenient method for determination of 1,25-dihydroxyvitamin D in human plasma. Arch Biochem Biophys. 1976 Sep;176(1):235–243. doi: 10.1016/0003-9861(76)90161-2. [DOI] [PubMed] [Google Scholar]
- FELLERS F. X., SCHWARTZ R. Etiology of the severe form of idiopathic hypercalcemia of infancy; a defect in vitamin D metabolism. N Engl J Med. 1958 Nov 27;259(22):1050–1058. doi: 10.1056/NEJM195811272592202. [DOI] [PubMed] [Google Scholar]
- Fraser D. R., Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970 Nov 21;228(5273):764–766. doi: 10.1038/228764a0. [DOI] [PubMed] [Google Scholar]
- Haussler M. R., Baylink D. J., Hughes M. R., Brumbaugh P. F., Wergedal J. E., Shen F. H., Nielsen R. L., Counts S. J., Bursac K. M., McCain T. A. The assay of 1alpha,25-dihydroxyvitamin D3: physiologic and pathologic modulation of circulating hormone levels. Clin Endocrinol (Oxf) 1976;5 (Suppl):151S–165S. doi: 10.1111/j.1365-2265.1976.tb03823.x. [DOI] [PubMed] [Google Scholar]
- Hendrix J. Z. Abnormal skeletal mineral metabolism in sarcoidosis. Ann Intern Med. 1966 Apr;64(4):797–805. doi: 10.7326/0003-4819-64-4-797. [DOI] [PubMed] [Google Scholar]
- Holick M. F., Schnoes H. K., DeLuca H. F., Suda T., Cousins R. J. Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine. Biochemistry. 1971 Jul 6;10(14):2799–2804. doi: 10.1021/bi00790a023. [DOI] [PubMed] [Google Scholar]
- Hughes M. R., Baylink D. J., Jones P. G., Haussler M. R. Radioligand receptor assay for 25-hydroxyvitamin D2/D3 and 1 alpha, 25-dihydroxyvitamin D2/D3. J Clin Invest. 1976 Jul;58(1):61–70. doi: 10.1172/JCI108459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- JACKSON W. P., DANCASTER C. A consideration of the hypercalciuria in sarcoidosis, idiopathic hypercalciuria, and that produced by vitamin D; a new suggestion regarding calcium metabolism. J Clin Endocrinol Metab. 1959 Jun;19(6):658–680. doi: 10.1210/jcem-19-6-658. [DOI] [PubMed] [Google Scholar]
- Kaplan R. A., Haussler M. R., Deftos L. J., Bone H., Pak C. Y. The role of 1 alpha, 25-dihydroxyvitamin D in the mediation of intestinal hyperabsorption of calcium in primary hyperparathyroidism and absorptive hypercalciuria. J Clin Invest. 1977 May;59(5):756–760. doi: 10.1172/JCI108696. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ponchon G., Kennan A. L., DeLuca H. F. "Activation" of vitamin D by the liver. J Clin Invest. 1969 Nov;48(11):2032–2037. doi: 10.1172/JCI106168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Powell L. W., Axelsen E. Corticosteroids in liver disease: studies on the biological conversion of prednisone to prednisolone and plasma protein binding. Gut. 1972 Sep;13(9):690–696. doi: 10.1136/gut.13.9.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raisz L. G., Trummel C. L., Holick M. F., DeLuca H. F. 1,25-dihydroxycholecalciferol: a potent stimulator of bone resorption in tissue culture. Science. 1972 Feb 18;175(4023):768–769. doi: 10.1126/science.175.4023.768. [DOI] [PubMed] [Google Scholar]
- Reiner M., Sigurdsson G., Nunziata V., Malik M. A., Poole G. W., Joplin G. F. Abnormal calcium metabolism in normocalcaemic sarcoidosis. Br Med J. 1976 Dec 18;2(6050):1473–1476. doi: 10.1136/bmj.2.6050.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SMITH D. W., BLIZZARD R. M., HARRISON H. E. Idiopathic hypercalcemia; a case report with assays of vitamin D in the serum. Pediatrics. 1959 Aug;24(2):258–269. [PubMed] [Google Scholar]
- Sinha T. K., DeLuca H. F., Bell N. H. Evidence for a defect in the formation of 1alpha,25-dihydroxyvitamin D in pseudohypoparathyroidism. Metabolism. 1977 Jul;26(7):731–738. doi: 10.1016/0026-0495(77)90060-9. [DOI] [PubMed] [Google Scholar]
- Sinha T. K., Miller S., Feming J., Khairi R., Edmondson J., Johnston C. C., Jr, Bell N. H. Demonstration of a diurnal variation in serum parathyroid hormone in primary and secondary hyperparathyroidism. J Clin Endocrinol Metab. 1975 Dec;41(06):1009–1013. doi: 10.1210/jcem-41-6-1009. [DOI] [PubMed] [Google Scholar]
- Stern P. H., Hamstra A. J., DeLuca H. F., Bell N. H. A bioassay capable of measuring 1 picogram of 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab. 1978 Jun;46(6):891–896. doi: 10.1210/jcem-46-6-891. [DOI] [PubMed] [Google Scholar]
- Stern P. H. Inhibition by steroids of parathyroid hormone-induced Ca45 release from embryonic rat bone in vitro. J Pharmacol Exp Ther. 1969 Aug;168(2):211–217. [PubMed] [Google Scholar]
- Stern P. H., Mavreas T. Bone-resorbing activity of analogues of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol: effects of side chain modification and stereoisomerization on responses of fetal rat bones in vitro. Mol Pharmacol. 1976 Nov;12(6):879–886. [PubMed] [Google Scholar]
- THOMAS W. C., Jr, MORGAN H. G., CONNOR T. B., HADDOCK L., BILLS C. E., HOWARD J. E. Studies of antiricketic activity in sera from patients with disorders of calcium metabolism and preliminary observations on the mode of transport of vitamin D in human serum. J Clin Invest. 1959 Jul;38(7):1078–1085. doi: 10.1172/JCI103884. [DOI] [PMC free article] [PubMed] [Google Scholar]