The Hydroxylation of Vitamin D on C25 in Thyrotoxicosis: The Role of the Activity of Microsomal Liver Enzymes

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.