High Calcitriol Levels Research Articles

Suppression of circulating calcitriol and duodenal active Ca transport by ketoconazole in pregnant rats.

Active Ca transport in the duodenum and the circulating level of calcitriol are elevated during pregnancy and lactation in the rat. Because calcitriol stimulates Ca transport in nonmated rats, we investigated its contribution to the increased transport during pregnancy and lactation. Rapid suppression of calcitriol from 28 +/- 3 to 8 +/- 0.4 pg/ml with the steroid hydroxylase inhibitor ketoconazole resulted in a 34% suppression of Ca transport in nonmated rats. At the end of pregnancy, when calcitriol concentration was suppressed from 64 +/- 7 to 12 +/- 2 pg/ml, the transport ratio decreased by 44%. Ca transport did not correlate with calcitriol levels between 40 and 80 pg/ml, suggesting a threshold level for maximal Ca transport stimulation. During lactation at even higher calcitriol levels, ketoconazole treatment again resulted in marked reduction in calcitriol from 124 +/- 1 to 71 +/- 12 pg/ml, but without any concurrent reduction in Ca transport in the duodenum. We conclude that in the vitamin D-replete rat the pregnancy-mediated, and probably also the lactation-mediated, increase in active Ca transport capacity is dependent on an increase in circulating calcitriol up to a certain threshold level.

Hypercalcemia Associated with Wegener’s Granulomatosis and Hyperparathyroidism: Etiology and Management

We report a case of hypercalcemia in a patient with coexisting hyperparathyroidism and Wegener's granulomatosis. Parathyroidectomy with removal of an adenoma resulted in a low parathyroid hormone level but high calcitriol levels and hypercalcemia persisted. In various granulomatous diseases, hypercalcemia has been shown to be the result of overproduction of 1,25-dihydroxy-vitamin D by disease-activated macrophages. Chloroquine has been demonstrated to effectively reduce the extrarenal synthesis of 1,25-dihydroxyvitamin D and serum calcium concentration in hypercalcemic patients with sarcoidosis. Hypothesizing that a similar mechanism would explain hypercalcemia in Wegener's granulomatosis as well, a therapeutic trial of chloroquine was initiated. The patient responded to chloroquine 500 mg twice daily with significant decreases in serum 1,25-dihydroxyvitamin D and calcium levels. This report extends previous observations of hypercalcemia associated with other granulomatous diseases to Wegener's granulomatosis and demonstrates an effective reduction of serum calcitriol and calcium levels in response to chloroquine therapy.

Atrial natriuretic factor levels in renal stone patients with idiopathic hypercalciuria and in healthy controls: The effect of an oral calcium load

Ionized calcium is a stimulator for the release of several peptide hormones. Atrial natriuretic factor (ANF) is a peptide hormone released from atrial tissue in response to atrial distension or volume expansion. In the present study, we have examined the effect of an oral calcium load in healthy controls and renal stone patients with idiopathic hypercalciuria. Our results demonstrated that ANF release increased in both groups in response to a calcium load. However, idiopathic hypercalciuric patients presented lower basal ANF levels in the presence of high calcitriol levels. The role of calcitriol on ANF release remains to be evaluated.