Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (1000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/- 5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls, 2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric stone formers (P = 0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate, delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Seasonal variations in vitamin D status and calcium absorption do not influence bone turnover in young women

OBJECTIVE: To evaluate the effect of seasonal variations in UV B-exposure on calcium absorption and bone turnover in young women with the overall goal to assess the potential benefit of a vitamin D supplementation during wintertime. DESIGN: Cross-sectional study. SETTING: Area of Bonn, Germany (51 degrees N). SUBJECTS: Thirty-eight women (24.5+/-0.5 y) studied in winter and 38 females of the same age (24.7+/-0.4 y) studied in summer. RESULTS: As estimated by a 4 d food record, both groups had similar dietary calcium and phosphorus intakes (> 1200 mg/d, respectively) covering actual recommendations. Significant reductions in serum concentrations of 25-hydroxyvitamin D (25OHD) and calcitriol, fractional calcium absorption (Fc220, measured by means of a stable strontium test), 24h urinary calcium and 24h urinary phosphorus excretion were observed during wintertime. 25OHD but not calcitriol was correlated with Fc220 values and with 24h urinary phosphorus excretion. Moreover, Fc220 was related to 24 h urinary calcium excretion. Fasting 2 h-urinary deoxypyridinoline concentrations (biomarker of bone resorption) and serum levels of carboxyterminal propeptide of type I procollagen (biomarker of bone formation) showed no differences between summer and winter. CONCLUSIONS: Our data indicate a decrease in intestinal calcium and phosphorus absorption during wintertime, most likely because of a reduction in serum 25OHD levels. Since bone turnover was not affected by the seasonal differences in mineral metabolism, there is no objective for young women with high calcium intake to supplement vitamin D during wintertime.     

Pregnancy after renal transplantation: 25 years experience in Spain

OBJECTIVES: To evaluate the kinetics of calcitriol (1,25(OH)2D3) administered subcutaneously. STUDY DESIGN: Calcitriol kinetics and efficacy after subcutaneous administration were studied in 13 CAPD patients with varying degrees of increased plasma levels of parathyroid hormone (i-PTH). A single dose of 2 micrograms of calcitriol was administered subcutaneously, and its serum levels at baseline and after 1, 2, 6, 12, and 24 hours were determined. Plasma ionized calcium and i-PTH were also determined at these periods. RESULTS: Serum calcitriol levels reached peak levels of 60 and 70 pg/mL at 1 and 2 hours after administration, respectively. These levels decreased thereafter, but remained above baseline values during 24 hours. The mean value of the area under the curve (AUC) was 809 +/- 226 pg/mL/hour. Plasma i-PTH levels showed a slight decrease after 1 and 2 hours, returning to baseline levels after this period. Plasma ionized calcium did not show significant changes during the study. A slight pain at the site of injection was mentioned by some patients. CONCLUSIONS: The subcutaneous route for calcitriol administration achieves theoretically adequate plasma levels in continuous ambulatory peritoneal dialysis (CAPD) patients. This is important when parenteral administration of calcitriol is considered in the treatment of secondary hyperparathyroidism.     

Developing habits and knowing what habits to develop: a look at the role of virtue in ethics

In vitro studies of parathyroid glands removed from dialysis patients with secondary hyperparathyroidism and hypercalcemia have demonstrated the presence of an increased set point of parathyroid hormone (PTH) stimulation by calcium (set point [PTHstim]), suggesting an intrinsic abnormality of the hyperplastic parathyroid cell. However, clinical studies on dialysis patients have not observed a correlation between the set point (PTHstim) and the magnitude of hyperparathyroidism. In the present study, 58 hemodialysis patients with moderate to severe hyperparathyroidism (mean PTH 780 +/- 377 pg/ml) were evaluated both before and after calcitriol treatment to establish the relationship among PTH, serum calcium, and the set point (PTHstim) and to determine whether changes in the serum calcium, as induced by calcitriol treatment, modified these relationships. Calcitriol treatment decreased serum PTH levels and increased the serum calcium and the setpoint (PTHstim); however, the increase in serum calcium was greater than the increase in the setpoint (PTHstim). Before treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium was r = 0.82, p < 0.001, and between the set point (PTHstim) and PTH was r = 0.39, p = 0.002. After treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium remained significant (r = 0.70, p < 0.001), but the correlation between the set point (PTHstim) and PTH was no longer significant (r = 0.09); moreover, a significant correlation was present between the change in the set point (PTHstim) and the change in serum calcium that resulted from calcitriol treatment (r = 0.73, p < 0.001). The correlation between the residual values (deviation from the regression line) of the set point (PTHstim), derived from the correlation between PTH and the set point (PTHstim), and serum calcium was r = 0.77, p < 0.001 before calcitriol and r = 0.72, p < 0.001 after calcitriol. In conclusion, the set point (PTHstim) increased after a sustained increase in the serum calcium, suggesting an adaptation of the set point to the existing serum calcium; the increase in serum calcium resulting from calcitriol treatment was greater than the increase in the set point (PTHstim); the set point (PTHstim) was greater in hemodialysis patients with higher serum PTH levels; and the correlation between PTH and the set point (PTHstim) may be obscured because the serum calcium directly modifies the set point (PTHstim).     

Intermittent calcitriol therapy in secondary hyperparathyroidism: a comparison between oral and intraperitoneal administration

BACKGROUND: Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism (secondary HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis (CCPD). METHODS: Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12 months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly. RESULTS: Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P < 0.0001, whereas serum phosphorus levels were higher in those given p.o. calcitriol, P < 0.0001. For the i.p. group, serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months. In contrast, serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o. calcitriol, P < 0.0001 by multiple regression analysis. Serum alkaline phosphatase levels were also lower in patients treated with i.p. calcitriol, P < 0.0001, but there was no difference between groups in the average dose of calcitriol given thrice weekly. The skeletal lesions of secondary HPT improved in both groups, 33% of patients developed adynamic bone lesion. CONCLUSION: Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol.     

Low calcium diet in hypercalciuric calcium nephrolithiasis: first do no harm

Many studies indicate that up-regulated production of 1,25(OH)2-vitamin D3 (calcitriol) with increased intestinal absorption of calcium is the primary event causing idiopathic hypercalciuria. Thus, a low calcium diet appears to be a straightforward strategy in calcium stone formers with hypercalciuria (HCSF). However, the efficacy of such a regimen has never been established, and lowering calcium intake from 1000 to 400 mg/day further enhances calcitriol production. On a diet chronically restricted in calcium, many stone formers increase their intake of animal flesh protein. The latter is known to increase renal mass, and calcitriol levels indeed are positively correlated with renal mass in animals as well as in HCSF. Thus, low calcium and high animal flesh protein consumption are independent stimuli for further up-regulation of calcitriol production. The rise in calcitriol suppresses parathyroid hormone synthesis thereby diminishing renal tubular calcium reabsorption, and increasing urinary calcium losses. Since calcitriol up-regulation also increases bone resorption, the combination of low calcium and high protein intake is particularly likely to induce negative calcium balance and thus osteopenia. Finally, low calcium intake carries the risk of insufficient intestinal binding of oxalate with subsequent increases in intestinal absorption and urinary excretion of oxalate. Indeed, most recent studies suggest that high amounts of calcium, when ingested simultaneously with oxalate-containing meals, are able to prevent hyperoxaluria during severe oral oxalate loading.     

Comparison of the sedative and amnesic effects of midazolam and propofol

OBJECTIVE: To determine normal serum bone-related biochemical variables in older African-Americans. DESIGN: A convenience sample of older African-Americans who had a health screening and blood testing for calciotropic hormones was compared with white Americans who were recruited at the end of the Systolic Hypertension in the Elderly Program (SHEP) study and were not on a thiazide diuretic. SETTING: Community-dwelling African-Americans who participated in SHEP or who attended one of two mass health screenings. PARTICIPANTS: Thirty-two African-Americans aged 68-93 years and 43 white Americans aged 70-89 years. MEASUREMENTS: Twenty-five hydroxyvitamin D (25OHD), parathyroid hormone, osteocalcin, and calcitonin. RESULTS: Serum 25OHD levels in 38% of the African-American men and 38% of African-American women were less than 8 ng/mL compared with 22% of Caucasian men and 40% of Caucasian women. Serum parathyroid hormone (PTH) was above the normal range in 25% of men and 33% of women of African-American descent and 14% of Caucasian men and 30% of Caucasian women. Serum 25OHD was lower (P < 0.05) in individuals with a previous history of fracture. Serum albumin (P < 0.05), calcitonin (P < 0.05), and osteocalcin (P < 0.05), but not 25OHD, were lower in African-Americans (men and women) when compared with Caucasians (P < 0.05). Serum calcium corrected for albumin was higher in the African-Americans than in the Caucasians (P < 0.05). As previously reported in Caucasians, PTH was inversely related to log 25OHD in African-Americans. Serum osteocalcin was positively correlated to PTH in African-Americans, as previously reported in Caucasians. Log 25OHD correlated inversely with osteocalcin in African-Americans, but this was not seen in Caucasians. CONCLUSIONS: In this limited sample, hypovitaminosis D (as assessed by 25OHD level) with secondary hyperparathyroidism occurred frequently in elderly African-Americans. Osteocalcin, a measure of osteoblast activity, correlated with 25OHD and parathyroid hormone. Osteocalcin serum levels were lower in African-Americans than Caucasians, but serum calcium corrected for albumin was higher in the former compared to the latter.     

The tale of parathyroid function in idiopathic hypercalciuria

At the origin, idiopathic hypercalciuria has been described as a syndrome consisting of normocalcemia, low plasma phosphate levels and abnormally high urinary calcium excretion. The cause of this syndrome was subject to many investigations throughout the years. Two main pathophysiologic hypotheses have been proposed: a) primary intestinal hyperabsorption of calcium, leading to depression of parathyroid hormone (PTH) secretion ("absorptive" hypercalciuria); and b) primary renal tubular leak of calcium which stimulates PTH secretion (secondary hyperparathyroidism). Most of the published studies indicate that intestinal hyperabsorption of calcium with subsequent relative hypoparathyroidism is the primary event causing idiopathic hypercalciuria, and that this occurs as a consequence of increased production of 1,25(OH)2-vitamin D3 (calcitriol). Fasting hypercalciuria, originally taken as evidence for a "renal leak" of calcium, appears to be, at least in part, the consequence of relative hypoparathyroidism.     

Effect of growth hormone on urine calcium and serum vitamin D metabolites in renal failure

Growth hormone (GH) causes a modest increase in urine calcium excretion in normal adults, but uremic rats given both GH and calcitriol developed hypercalciuria. Ten short prepubertal children with renal insufficiency treated with recombinant human GH (rhGH) had urine calcium to creatinine (Ca/Cr) ratios and serum vitamin D metabolite concentrations monitored prospectively for up to 24 months. Six were also treated with calcitriol and two with other vitamin D preparations. Mean urine Ca/Cr ratios or mean serum concentrations of 1,25-dihydroxy vitamin D, 24,25-dihydroxy vitamin D, and 25-hydroxy vitamin D did not change significantly during treatment with rhGH. The risk for rhGH-induced hypercalciuria is small in children with renal insufficiency, even when treated concomitantly with a vitamin D preparation.     

Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol

Intravenous calcitriol is known to directly suppress PTH secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum PTH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 +/- 0.02 (SEM) micrograms (0.015 micrograms/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calcium-phosphate products exceeded 60.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of fmrfamide gene neuropeptides is partly different in the embryonic nervous system of the pond snail, Lymnaea stagnalis L

The prevalence of hypercalcemia in patients with untreated tuberculosis (TB) varies widely between countries. Since the vitamin D status and calcium intake are important determinants of hypercalcemia in TB, these two factors were compared among four populations (U.K., Hong Kong, Malaysia, Thailand) with a low prevalence (<3%) and two populations (Sweden, Australia) with a high prevalence (>25%). In the three Asian countries, the circulating vitamin D levels are abundant, but the calcium intakes are low. Subjects from the U.K. have the lowest circulating vitamin D level of all, although their calcium intake is high. In Sweden and Australia, both the circulating vitamin D levels and calcium intakes are high. Since serum 1,25(OH)2D concentration will only be raised if its substance for extrarenal conversion, 25(OH)D, is plentiful and the effect of a given serum 1,25 (OH)2D concentration on serum calcium is determined by the calcium intake, it is postulated that the regional variation in the prevalence of hypercalcemia in TB may be due to differences in the circulating vitamin D levels and calcium intakes in these populations.     

Calciotropic hormones and nephrolithiasis

In recurrent calcium stone formers interfering factors or changes in receptor sensitivity may alter the interrelationships among calcium-regulating hormones, and hormonal behavior often does not fit with the theoretical assumptions. The vitamin D system appears to have the most important metabolic and clinical effects. Abnormal up-regulation of the synthesis of calcitriol and the consequent parathyroid hormone (PTH) suppression can induce hypercalciuria. Consequently, the hypocalciuric effect of thiazide would be caused by an enhanced response to PTH and by a reduction in 1,25(OH)2-vit D. A negative role of vitamin D on the skeleton has been observed in the presence of a negative calcium balance. Moreover, vitamin D also plays a role in urine oxalate excretion. PTH seems not to be directly stimulated in hypercalciuria and recurrent calcium nephrolithiasis, and patients with hyperparathyroidism and recurrent calcium nephrolithiasis show a similar degree of bone demineralization, irrespective of the presence of absence of the so-called 'primary hyperparathyroidism.' Calcitonin plays a contributory role in the pathogenesis of recurrent calcium nephrolithiasis that seems to be strictly related to dietary calcium intake. A higher sensitivity of thyroid C cells, particularly in absorptive hypercalciuric patients, could be related to the pathogenesis of hypercalciuria and contribute to its persistence.     

The functional status of the parathyroid in adult spasmophilia patients estimated by plasma parathormone assay

In 25 cases of spasmophilia the parathyroid function was assessed by complete exploration of the P-Ca metabolism and radioimmunoassay (RIA) of parathormone (PTH). Concomitantly the bone mineralization status was assessed by induced hypercalciuria tests and administration of 30 mg vitamin D2. RIA of PTH revealed increased values in 50% of the cases. The values fall within the range of secondary hyperparathyroidism, but this percentage varies with the values of the parathyroid function obtained by P-Ca metabolism explorations. The increased PTH values do no correlate with the level of plasma total calcium, ionic calcium, and magnesemia. Nor do they correlate with the bone mineralization disorders or the duration of the disease and the age of the patients.     

Design, construction, implementation, and cost of a hospital pharmacy cleanroom

The authors sought to clarify in a cross-sectional study the possible associations between homeostatic regulators of calcium and occupational exposure to lead. Subjects were 146 industrial male employees, 56 with and 90 without occupational lead exposure. The main outcome measures were serum concentration of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitriol). The median values of blood lead were 40.5 microg/dl in the exposed group and 4.0 microg/dl in the controls. There were no differences between groups in dietary history and serum calcium levels. PTH and calcitriol levels were significantly higher in the exposed than in the nonexposed subjects (42.0+/-24.2 vs. 33.6+/-14.9 pg/ml, p <0.05; and 83.8+/-27.0 vs. 67.9+/-17.6 pmol/liter, p <0.001, respectively). Multivariate analyses showed that after controlling for possible confounders, occupational lead exposure (no/yes) was independently associated with PTH level (pg/ml) (beta = 7.81, 95% confidence interval (CI) 3.7-11.5) and with calcitriol (pmol/liter) (beta = 12.3, 95% CI 3.84-20.8). It is concluded that subjects occupationally exposed to lead show a substantial compensatory increase in PTH and calcitriol activities which keep serum calcium levels within normal range. This may be of clinical significance since a sustained increase in calcitropic hormones in susceptible subjects may eventually increase the risk of bone disorders.     

Synthesis and QSAR of some 3-amino-2-(substituted)aminomethyl-5,6-disubstituted thieno[2,3-d]pyrimidin-4(3H)-ones as novel H1-receptor antagonists

The plasma concentrations of two bone matrix proteins (osteocalcin, osteonectin) were monitored in 56 samples from 14 patients receiving renal transplants and the values compared with serum bone alkaline phosphatase mass concentrations and osteotropic hormone levels (parathyroid hormone, calcitriol). There were no significant changes in the concentrations of plasma osteonectin at any time after transplantation, as compared with the values before transplantation (P > 0.1). None of the plasma samples showed osteonectin levels above the reference interval. There was a weak but significant relationship between platelet counts and plasma osteonectin levels (r = +0.322; P < 0.05). Osteocalcin showed a marked decrease of the values 1 week following transplantation as compared with the values before transplantation without further change of the values 1 and 3 months after transplantation (P > 0.5) whereas 3 months after transplantation bone alkaline phosphatase levels were higher than before transplantation (P < 0.05). Multiple regression analysis (performed with data from 42 samples obtained after transplantation) revealed serum creatinine as an independent predictor of plasma osteocalcin whereas serum calcitriol was an independent predictor of serum bone alkaline phosphatase (P < 0.05). No correlation was observed between serum calcitriol/plasma parathyroid hormone on the one hand and plasma osteocalcin on the other (P > 0.05). After transplantation there was a lack of correlation between serum bone alkaline phosphatase mass concentrations and plasma osteocalcin values (P > 0.05). In conclusion, serum bone alkaline phosphatase should be preferred to bone matrix proteins for the assessment of bone metabolism in patients receiving renal transplants: (a) bone alkaline phosphatase-but not osteocalcin-is significantly correlated with calcitriol and adequately reflects increased bone formation after renal transplantation; (b) interpretation of osteocalcin values is severely hampered by their strong correlation with serum creatinine concentrations; (c) plasma osteonectin determinations are not useful for monitoring bone formation.     

Immunoreactive parathyroid hormone, 25-hydroxycalciferol and bone histology in renal osteodystrophy (author's transl)

Immunoreactive parathyroid hormone (iPTH) and 25-hydroxycalciferol (25(OH)D) serum levels were determined in 32 patients with renal osteopathy, they were correlated with the results of bone biopsy and other clinical parameters. iPTH was closely related to bone histology, it did not correspond to serum calcium and alkaline phosphatase, but the correlation to serum phosphate was statistically significant. 25(OH)D levels were not related to the histological findings of osteomalacia or increased bone resorption, while a correlation between the vitamin D metabolite and serum calcium could be observed. Since iPTH and 25(OH)D levels exhibited a significant correlation, an inhibitory effect of 25(OH)D on parathyroid gland function in renal failure was discussed.     

Effect of porcine calcitonin in primary hyperparathyroidism (author's transl)

In order to investigate the effect of calcitonin (CT) on calcium and phosphorus metabolism in primary hyperparathyroidism (PHP), porcine calcitonin (80 MRC units) was injected intramuscularly at 9:00 a.m. and 5:00 p.m. for 10-14 days in 7 patients with parathyroid adenoma. Fasting blood specimens were drawn at 8:00 a.m. every other day and 24 hour urine samples were collected through out control and test days. To examine the acute effect of CT, blood and urine were checked several times until 8 hours after the first injection. A fall in the fasting serum calcium level observed in 5 patients during the repeated administrations of CT, as well as that observed in 6 patients within 6 hours after the first injection, showed a significant correlation with the initial serum calcium level. Serum phosphorus concentration decreased in all patients 6 hours after the first injection, while fasting levels seemed to remain unchanged. During the repeated administrations, urinary excretion of calcium and phosphrus decreased correspondingly with the fall in serum calcium levels, although no definite tendancy was observed within 8 hours after the first injection. Fasting serum PTH levels during the repeated administrations were measured in 2 patients. In a patient whose serum calcium returned to the initial level on the 7th day of administration, a gradual rise of PTH was observed, while in another patient whose serum calcium was kept lower than the initial level, PTH remained almost unchanged. These results indicate that, under such a condition where there is marked increase of bone resorption as PHP, repeated administrations of CT bring about not only a hypocalcemic effect but also the reduction of calcium and phosphorus excretion through a decreased filtered load. In addition, it was suggested that, in some cases of PHP, the hypocalcemic effect of CT may be abolished by an increase of PTH secretion from the parathyroid glands during long-term administration.     

Limitations of pulse oral calcitriol therapy in continuous ambulatory peritoneal dialysis patients

Calcitriol is increasingly used for therapy of secondary hyperparathyroidism in patients with end-stage renal disease. Its therapeutic efficacy, however, often has been limited by the associated increase in intestinal calcium and phosphorus absorption. Previous studies reported that these side effects could be avoided by intermittent administration of calcitriol in high doses, subsequently referred to as pulse therapy. The present study was designed to investigate pulse oral calcitriol therapy in a patient subgroup especially susceptible to the development of hypercalcemia and hyperphosphatemia under standard continuous calcitriol treatment. We examined 15 peritoneal dialysis patients with moderate degrees of hyperparathyroidism (intact parathyroid hormone [iPTH] levels, 150 to 903 pg/mL) ingesting between 1.5 and 6 g of calcium salts as the sole phosphate binders. Treatment consisted of 0.5 microgram calcitriol twice weekly. Eight of these patients had been previously converted to low calcium dialysate to tolerate the necessary doses of phosphate-binding calcium salts. During the study period, comprising 8 pretreatment weeks and 8 weeks of therapy, dialysates and doses of calcium salts were not changed, so that only calcitriol influenced the determined parameters. As expected, iPTH levels decreased rapidly in all patients (P < 0.0001). However, within 4 weeks of treatment a marked increase in calcium phosphorus products was observed (P < 0.0001). Overt hypercalcemia developed in five patients. We concluded that pulse oral calcitriol has to be carefully monitored in peritoneal dialysis patients receiving high doses of calcium salts because of the increased risk for hypercalcemia and hyperphosphatemia.     

Hypocalcemia following thyroid surgery: incidence and prediction of outcome

Postoperative hypocalcemia is a common and most often transient event after extensive thyroid surgery. It may reveal iatrogenic injury to the parathyroid glands and permanent hypoparathyroidism. We prospectively evaluated the incidence of hypocalcemia and permanent hypoparathyroidism following total or subtotal thyroidectomy in 1071 consecutive patients operated during 1990-1991. We then determined in a cross-sectional study which early clinical and biochemical characteristics of patients experiencing postoperative hypocalcemia correlated with the long-term outcome. Postoperative calcemia under 2 mmol/l was observed in 58 patients (5. 4%). In 40 patients hypocalcemia was considered severe (confirmed for more than 2 days, symptomatic or both). At 1 year after surgery five patients (0.5%) had persistent hypocalcemia. We found that patients carried a high risk for permanent hypoparathyroidism if fewer than three parathyroid glands were preserved in situ during surgery or the early serum parathyroid hormone level was /= 4 mg/dl under oral calcium therapy. When one or more of these criteria are present, long-term follow-up should be enforced to check for chronic hypocalcemia and to avoid its severe complications by appropriate supplement therapy.     

Topical calcitriol in the treatment of chronic plaque psoriasis: a double-blind study

A randomized, double-blind, left-right, vehicle-controlled study to assess the therapeutic efficacy and safety of twice daily application of 15 micrograms/g calcitriol ointment for a period of 6 weeks was performed in 32 patients suffering from bilateral, symmetrical, severe chronic plaque psoriasis. Twice daily 15 micrograms/g calcitriol ointment significantly improved erythema, induration, scaling and global severity of psoriatic plaques, and was much more effective than vehicle ointment. The difference in overall clinical efficacy between calcitriol and vehicle was statistically significant from week 1 onwards, and was maintained over the entire study. On completion of the study, clearance of psoriatic lesions was found in 47% of calcitriol-treated sides and in 13% of vehicle-treated sides. Skin histopathology of calcitriol-treated sides revealed a return to normal keratinization, with decreased inflammatory cell infiltration in the dermis and disappearance of the inflammatory infiltrate from the epidermis. Three patients had asymptomatic hypercalcaemia during the study. Mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus, 25-hydroxyvitamin D and calcitriol did not show statistically significant changes in the baseline/end-point comparisons.