The role of 1 alpha, 25-dihydroxyvitamin D in the mediation of intestinal hyperabsorption of calcium in primary hyperparathyroidism and absorptive hypercalciuria.

Abstract

A B S T R A C T The cause for the intestinal hyperabsorption of calcium (Ca) in various forms of hypercalciurias was explored by a careful measurement of plasma la,25-dihydroxycholecalciferol [la,25-(OH)2D] and by an assessment of intestinal Ca absorption and of parathyroid function. In 18 cases of primary hyperparathyroidism (PHPT), the mean plasma concentration of la,25-(OH)2D was significantly increased (4.9+2.2 SD ng/dl vs. 3.4+0.9 ngldl for the control group), and was significantly correlated with fractional Ca absorption (a) (r = 0.80, P < 0.001). Plasma la,25-(OH)2D was also correlated with urinary Ca (P < 0.05), but not with serum Ca or phosphorus (P), P clearance, urinary cyclic AMP, or serum immunoreactive parathyroid hormone. In 21 cases of absorptive hypercalciuria (AH), plasma la,25-(OH)2D was elevated in onethird of cases, and the mean value of 4.5±+1.1 ng/dl was significantly higher than that of the control group (P < 0.01). Since relative hypoparathyroidism may be present, the normal absolute value of plasma la,25-(OH)2D, found in two-thirds of cases of AH, may be considered to be inappropriately high. Moreover, in the majority of cases of AH, the data points relating plasma la,25-(OH)2D and a fell within 95% confidence limits of values found in non-AH groups (including PHPT). The results suggest that the intestinal hyperabsorption of Ca in PHPT and AH may be vitamin D dependent. However, the disturbance in vitamin D metabolism may not be the sole cause for the high Ca absorption in AH, since in some patients with AH, the intestinal Ca absorption appears to be

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“…Although the serum iPTH level was two three times more than the age-adjusted normal mean, serum ionized and total calcium values were in the lower half of the normal range and seum1, 25-(OH) 2D was in the low-normal range. Because patients with primary hyperparathyroidism and comparable increase in serum1, 25 (OH) 2D concentrations (Kaplan et al, 1977), values in these patients seem inapporopriately low and are compatible with the hypothesis that the secondary hyperparathyroidism was caused by inadequate conversion of 25-OH-D to1, 25-(OH) 2D.…”

Pathophysiology of spontaneous hypercalciuria in laboratory rats. Role of deranged vitamin D metabolism.

“…Thus, the renal leak theory is not supported by the frequent normal (5,12,15) or suppressed (4,8,10,14,19) parathyroid hormone levels. Urinary cAMP and fasting urine Ca to creatinine ratio (2,19,25) were elevated in only a minority of the IH patients (5,8,19).…”

“…Recently, it was hypothesized that the primary defect may reside in the disordered regulation of 1,25(OH)2D3 production (1,10,14), as suggested by the absolutely or relatively elevated serum 1,25(OH)2D3 levels in these patients (4,10,13,14,21,23,25,28). When Ca intake is adequate, hyperabsorption predominates, and is expressed essentially as absorptive hypercalciuria.…”

New Insights Into the Pathogenesis of Idiopathic Hypercalciuria

“…One potential mechanism for increased absorption may be the higher levels of serum calcitriol found in patients with IH compared to normal subjects in many studies ( Figure 1, panel b) [9;10]. Calcitriol upregulates expression of calcium transport proteins in the intestine, including the apical calcium channel, TRPV6 [13], and calcium absorption is directly related to calcitriol levels [14]. In some hypercalciuric subjects, however, intestinal calcium absorption appears to be increased out of proportion to the calcitriol level [14].…”

“…Calcitriol upregulates expression of calcium transport proteins in the intestine, including the apical calcium channel, TRPV6 [13], and calcium absorption is directly related to calcitriol levels [14]. In some hypercalciuric subjects, however, intestinal calcium absorption appears to be increased out of proportion to the calcitriol level [14]. Patients with IH maintain normal fasting serum calcium levels, and PTH levels have generally been reported as normal or slightly low [15].…”