Expression of the vitamin D receptor (VDR) in the parathyroid glands is decreased in secondary hyperparathyroidism associated with chronic renal failure by undefined mechanisms. In the present study, we examined the effects of hyperparathyroidism and dietary calcium and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on the expression of VDR in rat parathyroid glands. Vitamin D-deficient rats were maintained on diets containing 0.02% Ca (-D, LCD), 0.4% Ca (-D, NCD), or 2.0% Ca (-D, HCD) for 6 weeks. Serum ionized Ca (ICa) in the rats on the three diets ranged from 2.5-5.2 mg/dl. Serum PTH ranged from 22-590 pg/ml and correlated inversely with ICa (r = -0.835; P < 0.001). Rats with the highest ICa had normal PTH values, suggesting that vitamin D deficiency per se does not lead to hyperparathyroidism. VDR messenger RNA (mRNA) levels in the parathyroid glands correlated positively with ICa (r = 0.845; P < 0.001) and negatively with PTH (r = -0.716; P < 0.001). VDR mRNA levels in the rats fed the -D, HCD were 6 times higher than those receiving -D, LCD and the same as those in rats fed a normal (Purina) diet. Thus, prevention of hyperparathyroidism with high dietary calcium prevented the drop in VDR expression. Treatment of the rats on all three diets with 0, 25, or 100 ng 1,25-(OH)2D3, ip, 48 and 12 h before death dose dependently increased ICa and decreased PTH, as expected, and also increased parathyroid gland VDR mRNA. This coordinate regulation of VDR mRNA by calcium and 1,25-(OH)2D3 was also observed in the kidney, but intestinal VDR mRNA was not stimulated by dietary calcium or 1,25-(OH)2D3. Analysis of covariance for parathyroid gland VDR mRNA and ICa for the three doses of 1,25-(OH)2D3 revealed no significant independent effect of 1,25-(OH)2D3 on VDR mRNA, suggesting that the up-regulation of VDR expression by 1,25-(OH)2D3 in the parathyroid glands may be mediated primarily by increasing serum calcium.
An assessment of free and total calcium measurements was made in 691 patients with suspected hypercalcemia or disorders often associated with hypercalcemia. In 18.9% of the 1049 specimens analyzed from nine different patient groups, a different impression of hypercalcemia was obtained depending on whether the free or total calcium was considered. Analysis of the ratio of free to total calcium indicated that there are two main factors which influence the distribution of calcium in the serum of hypercalcemic patients: the concentrations of albumin and parathyroid hormone. A lowered albumin concentration accounted for the altered distribution of calcium in patients with malignancies and partially accounted for the altered distribution in patients postrenal transplantation. In patients with confirmed primary hyperparathyroidism a higher ratio of free to total calcium was found, which could not be explained by alterations in protein, albumin, pH, or CO2 content but was related to parathyroid hormone concentration. Free calcium appears to be a slightly better indicator of elevated calcium states than total calcium. Measurements of free calcium should be particularly useful in patients with altered albumin concentration, with multiple myeloma in whom a calcium-binding protein could be present, after renal transplantation, and with suspected hyperparathyroidism and normal or slightly elevated total calcium values. (J Clin Endocrinol Metab48: 393, 1978)
Patients with the nephrotic syndrome and normalrenal function have low levels of 25(OH)D in serum presumablydue to the loss of this metabolite in the urine. Osteomalaciaand hyperparathyroidism have been recently reported to occuras a consequence of those low levels of 25-hydroxyvitamin D(25OHD). We studied six patients (aged 26–52yr) with thenephrotic syndrome (mean duration, 6.7 yr; range, 2–12 yr) andnormal renal function, and evaluated their calcium, phosphorus,PTH, and vitamin D metabolite levels. Bone biopsies wereobtained in all patients. The creatinine clearance ranged from83-134 ml/min-1.73 m2 of body surface, serum albumin was 2.65± 0.42 (±SD) g/100 ml, and proteinuria ranged from 3.5–3.2 g/24 h. All patients had normal serum magnesium, phosphorus,ionized calcium, and alkaline phosphatase (total and bone fraction),and normal roentgenographic metabolic bone survey.Serum PTH, measured by the carboxy-terminal RIA, was 5.1±2.3 μleq/ml (normal, 2–10), serum 25OHD was 8.8 ± 4.0 ng/ml(normal, 15–30), and 1,25-dihydroxyvitamin D3 was 38 ± 25 pg/ml (normal, 17–58). Serum vitamin D-binding protein was 420± 42 μg/ml (normal, 400–800). The histological appearance ofbone biopsies obtained in these patients was not different fromthat in a group of sex- and age-matched controls. Specifically,there was no increase in the volume of osteoid (unmineralizedbone), the percentage of trabecular surface covered by osteoid,or the number of osteoclasts. The cellular rate of mineralizationwas normal in all six patients. Thus, these data indicate thatlow serum levels of 25OHD in patients with the nephroticsyndrome and normal renal function do not necessarily resultin the development of osteomalacia and/or hyperparathyroidism.(J Clin Endocrino Metab56: 496, 1983)
Quiz of the Month AnswerThe patient was resuscitated with fluids and dopa mine.Because of the sudden hypotension and decreased cardiac sounds an emergency echocardiogram was ob tained which showed pericardial fluid.An emergency periocardiocentesis yielded 250 cm3 of bright red blood which clotted.The patient's blood pressure dramatically improved.He required no further fluid support.Over the next 24 h he reaccumulated pericardial fluid requiring a pericardial window.Life-threatening complications of subclavian catheter insertion have been previously described [1].Cardiac tamponade secondary to superior vena cava or right atrial puncture, though rare, can occur [2][3][4][5].The diag nostic approach on this patient included a dye study through the subclavian catheter, echocardiographic eval uation with microbubbles through the subclavian cathe ter, and direct visual inspection at thoracotomy.All failed to reveal the lesion causing tamponade.However, it was still felt that the tamponade was traumatic and secondary to subclavian catheter placement.The reasons for this conclusion are: (1) the timing of the tamponade which was within 10 min of cathether placement; (2) the bright red blood aspirated from the pericardium with clots, and (3) spun hematocrit from the pericardial fluid yielded the same values as a systemic hematocrit.Sudden hemodynamic decompensation after subcla vian catheter placement should bring to mind cardiac tamponade as a diagnosis to be considered.
