ABSTRACT Vitamin D3 after its entrance in the organism undergoes hydroxylation on C-25 carbon atom by the action of microsomal liver enzymes giving the metabolite 25 hydroxyvitamin D3 (25OHD3). The function of microsomal liver enzymes is influenced in some specified states by hormones or drugs. It has approved that thyroxin is a potent stimulator of these enzymes while allopurinol suppresses their function. The aim of this issue is to examine 25OHD3 plasma levels in thyrotoxic subjects and in those pretreated with allopurinol on the base of the afford mentioned data. In a first phase 25OHD3 plasma levels were estimated in thyrotoxic subjects against euthytoid healthy controls. In a second phase lmg vitamin D3 was injected intravenously (i.v.) in thyrotoxic subjects and in healthy euthyroid controls. 25OHD3 plasma levels were measured before and in post injection period in six hours intervals for 48 hours. In a third phase a couple of subjects one thyrotoxic and one euthyroid healthy control pretreated both with allopurinol injected lmg of vitamin D3 i.v. In all studied subjects 25OHD3 plasma levels were measured before and in post injection period in six hours intervals for 48 hours. The pre and post injection 25OHD3 plasma levels measured the size of activity of liver enzyme responsible for bioactivation of vitamin D3. In the first phase was indicated that 25OHD3 plasma levels were lower in thyrotoxic subjects comparing with that of euthyroid healthy controls (p < 0.001). In the second phase was found that the bioactivation of vitamin D3 in thyrotoxic subjects was 2,5 to 8 times faster comparing with euthyroid healthy controls. In the third phase was shown that allopurinol decreases the activity of liver enzymes function as regard the bioactivation of vitamin D3. The bioactivation of vitamin D3 is accelerated in thyrotoxicosis compared with that in euthyroid state. This phenomenon produces low 25OHD3 plasma levels in thyrotoxic subjects which initially may be normal or slightly increased depended from the vitamin D3 status in the thyrotoxic subjects. By continuous stimulatory action of increased thyroid hormones on liver enzymes the 25OHD3 plasma levels earlier or later decline in levels of hypo-or avitaminosis D3. The previously described biological events may explain the decreased intestinal calcium absorption of vitamin D3 and the osteomalacic component found in a percentage of thyrotoxic bone histology. For the blocking effects of allopurinol on liver enzymes function and possibly of other pharmaceutical products in relation to vitamin D3 bioactivation, available data are still lacking.
Cite this paper
C. G. Velentzas, "The Hydroxylation of Vitamin D on C25 in Thyrotoxicosis The Role of the Activity of Microsomal Liver Enzymes," International Journal of Clinical Medicine, Vol. 3 No. 4, 2012, pp. 295-299. doi: 10.4236/ijcm.2012.34057.
 J. G. Haddad and K. J. Chyu, “Competitive Protein-Binding Radioassay for 25-Hydroxycholecalciferol,” Journal of Clinical Endocrinology & Metabolism, Vol. 33, No. 6, 1971, pp. 992-995. doi:10.1210/jcem-33-6-992
 A. J. Ronver and K. O. O’ Brien, “Hypovitaminosis D among Healthy Children in the United States,” Archives of Pediatrics & Adolescent Medicine, Vol. 162, No. 6, 2008, pp. 513-519. doi:10.1001/archpedi.162.6.513
 C. Velentzas, D. G. Oreopoulos, G. From, B. Porret and A. Rapaport, “Vitamin D Levels in Thyrotoxicosis,” Lancet, Vol. 1, 1977, pp. 370-371.
 H. J. W. Cleeve and R. F. Brown, “Plasma 25-Hydroxy-vitamin D and Alkaline Phosphate Isoenzymes In Hyperthyroidism,” Annals of Clinical Biochemistry, Vol. 15, No. 6, 1978, pp. 320-323.
 W. Hunstein, K. H. Gless, H. Schmidt-Gayk, G. V. Mittelstaedt and M. Hufner, “Alka-line Phosphatase and Plasma 25 OH Vitamin D in Hyperthyroidism,” Hormone and Metabolic Research, Vol. 9, No. 6, 1977, pp. 532- 533. doi:10.1055/s-0028-1095592
 R. Bouillon, E. Muls and P. DeMoor, “Influence of Thyroid Function on the Serum Concentration of 1.25 Dihydroxyvitamin D,” Journal of Clinical Endocrinology & Metabolism, Vol. 51, 1980, pp. 793-797.
 E. Keck, H. Peerenboom, H. J. Graf, H. V. Lilienfled-Toal and H. L. Kruskemper, “Vitamin D Metabolites in Hyperthyroidism,” Acta Endocrinologica, Vol. 96, 1980, p. 36.
 I. A. MacFarlane, E. B. Mawer, J. Berry and J. Hann, “Vitamin D Metabolism in Hypethyroidism,” Clinical Endo-crinology, Vol. 17, No. 1, 1982, pp. 51-59.
 L. Mo-sekild, B. Lund, O. H. Sorensen, M. S. Christensen and F. Melsen, “25-Hydroxycholecalciferol in Hyperthyroidism,” Lancet, Vol. 1, 1977, pp. 806-807.
 C. G. Velent-zas, “Some Observation on Vitamin D3 Metabolism in Thyrotoxicosis,” Acta Vitamin Enzyme, Vol. 5, 1983, pp. 159-163.
 M. F. Holick, E. S. Siris, N. Binkley, M. K. Beard, A. Khan, J. T. Katzer, et al., “Prevalence of Vitamin D Inadequacy among Postmenopausal North Ameri-cans Women Receiving Osteoporosis Therapy,” Journal of Clinical Endocrinology & Metabolism, Vol. 90, No. 6, 2005, pp. 3215-3224. doi:10.1210/jc.2004-2364
 J. Adams and M. Hewison, “Update in Vitamin D,” Journal of Clinical Endocrinology & Metabolism, Vol. 95, No. 2, 2010, pp. 471-478. doi:10.1210/jc.2009-1773
 K. Heaney, “Functional Indices of Vitamin D Status and Ramifications of Vitamin D Deficiency,” American Journal of Clinical Nutrition, Vol. 80, No. 6, 2004, pp. 1706-1709.
 M. Holick, “MrOs Is D-Ficient,” Jour-nal of Clinical Endocrinology & Metabolism, Vol. 94, No. 4, 2009, pp. 1092-1093. doi:10.1210/jc.2009-0388
 M. F. Holick, “Vitamin D Deficiency,” New England Journal of Medicine, Vol. 357, No. 3, 2007, pp. 266-281.
 B. C. Hollis, “Circu-lating 25-Hydroxyvitamin D Levels Indicative of Vitamin D Sufficiency: Implication for Establishing a New Dietary Intake. Recommendation for Vitamin D,” Journal of Nutrition, Vol. 135, No. 2, 2005, pp. 317-322.
 D. W. Hollis and C. L. Wagner, “Normal Serum Vitamin D Levels,” New England Journal of Medicine, Vol. 352, 2005, pp. 515-516. doi:10.1056/NEJM200502033520521
 E. Orwall, C. M. Nielsen, L. M. Marschall, L. Lambert, K. F. Holton, A. R. Hoffman, et al., “Vitamin D Deficiency in Older Men,” Journal of Clinical Endocrinology & Metabolism, Vol. 94, No. 4, 2009, pp. 1214-1222.
 C. G. Velentzas, “Vitamin D and Thyroid Hormones,” In: S. R. Malone, Ed., Vitamin D: Nutrition Side Effects and Supplements, 2009, pp. 175-184.
 J. Crooks, A. J. Hedley, C. MacNee and I. H. Stevenson, “Changes in Drug Metabolizing Ability in Thyroid Diseases,” British Journal of Pharmacology and Chemotherapy, Vol. 49, 1973, pp. 156-157.
 M. Eichelbaum, G. Bodem, R. Gugler, C. Schneider-Deters and H. J. Dengler, “Influence of Thyroid Status on Plasma Half-Life of Antipyrine in Man,” New England Journal of Medicine, Vol. 290, No. 19, 1974, pp. 1040-1042. doi:10.1056/NEJM197405092901902
 P. Saenger, A. B. Rifkind and M. I. New, “Changes in Drug Metabolism in Children with Thyroid Disorders,” Journal of Clinical Endocrinology & Metabolism, Vol. 42, No. 1, 1976, pp. 155-159. doi:10.1210/jcem-42-1-155
 E. S. Vesell, I. Passananti and F. E. Green, “Impairment of Drug Meta-bolism in Man by Allopurinol and Nortriptyline,” New England Journal of Medicine, Vol. 283, No. 27, 1970, pp. 1484-1488.
 J. D. Baxter and P. K. Bondy, “Hypercalcemia of Thyrotoxicosis,” Annals of Internal Medicine, Vol. 65, 1960, pp. 249-442.
 T. F. Davies and P. R. Larsen, “Thyrotox-icosis,” 11th Edition, In: H. M. Kronenberg, S. Melmed, K. S. Polonsky and P. R. Larsen, Eds., Williams Textbook of Endocrinology, Saunders, 2008, pp. 333-375.
 D. Frizel, A. Malleson and V. Marks, “Plasma Levels of Ionized Calcium and Magnesium in Thyroid Disease,” Lancet, Vol. 45, 1967, pp. 269-273.
 D. H. Smith, S. A. Frazer and G. M. Wilson, “Hyperthyroidism and Calcium Metabolism,” Clinical Endocrinology & Metabolism, Vol. 2, 1973, pp. 333-354.
 C. R. Kleeman, S. Tuttle and S. H. Basset, “Metabolic Observation in a Case of Thyrotoxicosis with Hypercalcemia,” Journal of Clinical Endocrinology & Metabolism, Vol. 18, No. 5, 1958, pp. 477-491.
 P. Singhelakis, C. Alevizaki and D. Ikkos, “Intestinal Calcium Absorption in Hyperthyroidism,” Metabolism, Vol. 63, 1974, pp. 311-321.
 P. B. Cook, J. R. Nassim and J. Collins, “The Effects of Thyrotoxicosis upon the Metabolism of Calcium Phosphorus and Nitrogen,” Quarterly Journal of Medicine, Vol. 28, No. 4, 1959, pp. 505-519.
 O. L. M. Bijvoet and C. L. H. Majoor, “The Renal Tubular Reabsorption of Phosphate in Thyrotoxicosis,” Clinica Chimica Acta, Vol. 11, 1965, pp. 181-183.
 B. Malamos, P. Sfikakis and P. Pandos, “The Renal Handling of Phosphate in Thyroid Disease,” Journal of Endocrinology, Vol. 45, No. 2, 1969, pp. 269-273.
 A. M. Parfit and C. E. Dent, “Hyperthyroidism and Hypercalcemia,” Quarterly Journal of Medicine, Vol. 39, 1970, pp. 171-187.
 P. H. Adams, J. Jowsey, P. J. Kelly, L. Riggs, V. R. Kinney and J. D. Jones, “Effects of Hyperthyroidism on Bone and Mineral Metabolism in Man,” Quarterly Journal of Medicine, Vol. 36, 1967, pp. 1-15.
 J. Auwerx and R. Bouillon, “Mineral and Bone Metabolism in Thyroid Diseases. A Review,” Quarterly Journal of Medicine, Vol. 60, 1986, pp. 737-752.
 L. Mosekilde, E. F. Eriksen and P. Charles, “Effects of Thyroid Hormone on Bone and Mineral Metabolism,” Endocrinology and Metabolism Clinics of North America, Vol. 19, 1990, pp. 35-63.
 C. Velentzas and D. G. Oreopoulos, “Thyrotoxic Osteodystrophy: A Perplexing Type of Metabolic Bone Disease,” Clinical and Investigative Medicine, Vol. 1, 1978, pp. 53-55