24-25-dihydroxyvitamin-d-3 and Hypercalcemia

Excessive vitamin D causes marked and prolonged hypercalcemia by accelerating intestinal calcium absorption and bone resorption. Vitamin D induced hypercalcemia includes the toxic ingestion of excessive amount of vitamin D preparations, granulomatous diseases and lymphoproliferative malignancies. In vitamin D toxicity, the clinical courses vary depending on the vitamin D preparation responsible for the hypercalcemia. Hypercalcemia state continues for several months when D2 or D3 are responsible for the toxicity whereas the hypercalcemia would subside in a week when 1 alpha(OH) D3 or 1,25 (OH)2D3 are responsible for the toxicity. Abnormal calcium metabolism can be treated by hydration and glucocorticoids. Hypercalcemia is associated with variety kinds of granulomatous diseases, including sarcoidosis and tuberculosis. The granulomatous tissue is believed to be the site of the ectopic production of 1,25(OH)2D3 in which the regulation of the synthesis is quite different from that in the normal kidney. Glucocorticoid markedly diminishes the synthesis. Hypercalcemia associated with elevated serum 1.25(OH)2D3 levels is also found in patients with lymphomas and some other malignancies. However, there still are not sufficient evidences to prove that the excessive amount of endogenous 1.25(OH)2D3 is the primary cause of the hypercalcemia.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Humans; Hypercalcemia; Sarcoidosis; Tuberculosis; Vitamin D

The available data with regard to the use of calcitriol, 1 alpha-hydroxyvitamin D3 (1 alpha-OH D3), and 24,25-dihydroxyvitamin D3 (24,25-[OH]2D3) in the management of chronic renal insufficiency are reviewed. Patients with mild to moderate osteitis fibrosa experience substantial improvement with either calcitriol or 1 alpha-OH D3 therapy. However, few patients experience a reversal to normal in histologic characteristics of bone. The conditions of patients with osteomalacia do not respond to either calcitriol or 1 alpha-OH D3 therapy. The bone lesion appearing in these patients is most likely a toxic effect of aluminum. The prognosis is usually poor, but the conditions of some patients may respond to administration of 24,25-(OH)2D3 together with calcitriol. Preliminary data suggest that use of chelating agents may be beneficial. In this group of patients, 24,25-(OH)2D3 administration together with calcitriol may be beneficial.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Alkaline Phosphatase; Animals; Bone and Bones; Calcitriol; Chelating Agents; Child; Densitometry; Dihydroxycholecalciferols; Drug Therapy, Combination; Humans; Hydroxycholecalciferols; Hypercalcemia; Kidney Failure, Chronic; Magnesium; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Hormone; Phosphates; Prognosis; Radiography; Rats; Renal Dialysis

The effect of combined administration of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) and 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) was studied in 24 non-dialyzed patients with chronic renal insufficiency (CRI), matched pairwise as to age, sex, and creatinine clearance (Cr.cl). Low Ca intake had been supplemented beforehand. Then, 1 alpha-(OH)D3 (mean dose 0.55 micrograms daily) was given orally to all patients for 3 months (T0 to T3). Subsequently, patients were assigned randomly to 6 months further treatment either with 1 alpha-(OH)D3 alone (Group A) or with 1 alpha-(OH)D3 plus a high dosage of 24,25-(OH)2D3 (50 micrograms orally, twice weekly) (Group B). Histomorphometry was performed at T0, T3, and T9. In both groups iPTH was equally suppressed, into the lower normal range. Whereas in Group A, serum Ca rose steadily and Cr.cl declined, in Group B both parameters levelled off between T6 and T9. At T9, in Group A the elevated resorption and osteoid indices had normalized markedly, but osteoblasts (Ob.Pm) and mineralizing boundaries (M.Bd) were depressed considerably between T3 and T9. In contrast, in Group B, preservation of Ob.Pm and improved mineralizing activity were observed (M.Bd at T9 > T3 > T0). Resorption indices hardly changed. In the patients with high Ob.Pm at T0, cancellous bone area increased significantly. This was not observed in Group A. Thus, in Group B, osteoblast recruitment appeared maintained and M.Bd appeared normalized. Decline of remodeling toward an adynamic state with an increased risk of hypercalcemia appeared prevented.

Topics: 24,25-Dihydroxyvitamin D 3; Administration, Oral; Adult; Bone Density; Bone Remodeling; Bone Resorption; Calcium; Drug Therapy, Combination; Female; Humans; Hydroxycholecalciferols; Hypercalcemia; Ilium; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis

The present study examined the effect of intermittent oral high doses of 1-alpha-OHD3 in combination with a pharmacological dose of 24,25(OH)2D3 on parathyroid hormone (PTH) secretion. Twenty hemodialysis (HD) patients (10 males, aged 26-72 years, on regular hemodialysis for 7-128 months) with secondary hyperparathyroidism resistant to long-term low-dose 1-alpha-OHD3 therapy were studied for 24 weeks. At the outset of the study they were randomly divided into two groups: group 1 received high-dose 1-alpha-OHD3 plus 24,25(OH)2D3 (2 x 5 micrograms/day) and group 2 was on monotherapy with 1-alpha-OHD3. 1-alpha-OHD3 was given three times a week in the evening before each HD in gradually increased doses from 1 to 4 micrograms adjusted to keep serum calcium levels below 2.6 mmol/L. During the therapy mean serum calcium and ionized calcium levels increased but remained in the normal ranges without differences between the two groups. However, the frequency of hypercalcemia episodes was different in the two groups. In the first 12 weeks the number of hypercalcemia episodes was significantly lower in group 1 than in group 2 (6 vs. 12; p < .05), allowing the use of significantly higher 1-alpha-OHD3 doses in group 1. In the second 12 weeks of the study the 1-alpha-OHD3 dose in group 1 had to be reduced due to more frequent appearance of hypercalcemia. So, the 1-alpha-OHD3 doses became similar in the two groups during the second 12 weeks of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 24,25-Dihydroxyvitamin D 3; Administration, Oral; Adult; Aged; Calcium; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hydroxycholecalciferols; Hypercalcemia; Hyperparathyroidism; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis

The circulating concentrations of calcium, phosphorus, and vitamin D metabolites were measured in 25 infants (fifteen to 30 days of age) with congenital hypothyroidism before treatment or during the first 6 months of thyroxine therapy. Five of the children before treatment and four during the early 3 months of treatment had mild hypercalcemia (10.8 to 12.4 mg/dl). Hypercalcemia before treatment did not appear to be related to the vitamin D status of the infant nor to an alteration in vitamin D metabolism, but to the presence of a residual thyroid secretion. In contrast, hypercalcemia during thyroxine therapy was related to vitamin D supplementation, even though the serum calcium concentration could not be correlated with the circulating concentration of any of the vitamin D metabolites assayed and obvious changes in vitamin D metabolism could not be demonstrated.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Alkaline Phosphatase; Calcitriol; Calcium; Congenital Hypothyroidism; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hypercalcemia; Hypothyroidism; Infant, Newborn; Phosphorus; Thyroid Hormones; Thyrotropin; Thyroxine; Time Factors; Vitamin D

Twenty-three patients with end-stage renal failure on maintenance haemodialysis were treated with 1,25-dihydroxy vitamin D3 or 24-25-dihydroxy vitamin D3 for 3-32 months (total 232 patient months). Treatment with 1,25-dihydroxy vitamin D3 was marked by symptomatic, biochemical and histological improvements in the majority of patients. In contrast, treatment with 24,25-dihydroxy vitamin D3 produced no biochemical or histological improvements and such patients developed severe symptomatic bone disease. Successful renal transplantation resulted in rapid improvement in symptoms, biochemistry and bone histology in nine of 10 patients irrespective of whether prior treatment was with 1,25-dihydroxy vitamin D3, 24,25-dihydroxy vitamin D3 or both. During treatment with 1,25-dihydroxy vitamin D3 progressive reduction in dosage was required in the majority of patients because of hypercalcaemia, which was rapidly corrected by stopping treatment for a few days. Hypercalcaemia did not occur until serum alkaline phosphatase (AP) and amino terminal parathyroid hormone (N-PTH) had fallen towards normal. Treatment failure was uncommon in 1,25-dihydroxy vitamin D3-treated patients and was characterized by the early development of hypercalcaemia. Addition of 24,25-dihydroxy vitamin D3 in such patients rendered the hypercalcaemia more manageable but did not lead to any further improvement in biochemistry or bone histology. Treatment with 24,25-dihydroxy vitamin D3 was accompanied by the development of severe symptomatic bone disease in the majority of patients and a characteristic pattern of biochemical abnormalities with hypocalcaemia and rises in AP and N-PTH. Substitution of 1,25-dihydroxy vitamin D3 treatment for 24,25-dihydroxy vitamin D3 in these patients resulted in prompt improvement in clinical, biochemical and histological abnormalities. Successful renal transplantation was accompanied by rapid resolution of clinical, biochemical and histological features of renal osteodystrophy irrespective of whether previous treatment was with 1,25-dihydroxy vitamin D3 or 24,25-dihydroxy vitamin D3. Hypophosphataemia was common in the early months after renal transplantation without evidence of continuing hyperparathyroidism. The studies have confirmed that 1,25-dihydroxy vitamin D3 is effective in controlling clinical, biochemical and histological features of renal osteodystrophy while 24,25-dihydroxy vitamin D3 did not have a useful therapeutic effect in the dose used.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Bone and Bones; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydroxycholecalciferols; Drug Therapy, Combination; Humans; Hypercalcemia; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Time Factors

In sarcoidosis, renal involvement includes hypercalcemia-related nephrocalcinosis and granulomatous tubulointerstitial nephritis. Hypercalcemia is thought to be due to increased production of 1,25 dihydroxyvitamin D (1-25D), but 1-25D levels have not been evaluated in sarcoidosis patients with renal dysfunction.. We enrolled 9 sarcoidosis patients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosis patients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90).. Serum calcium and 1-25D levels were significantly higher in the sarcoidosis patients than in the non-sarcoidosis patients (p < 0.01 and p = 0.01, respectively). There was a positive correlation between 1-25D and eGFR in the patients without sarcoidosis (r = 0.693; p < 0.01). As the renal function of sarcoidosis patients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosis patients. On renal biopsy, CD68 staining was positive for tissue macrophages in all 8 patients who had tubulointerstitial nephritis (with or without typical granulomas), while Von Kossa staining showed calcification of tubules near or inside granulomas in 6 of these 8 patients.. While tissue macrophages promote development of tubulointerstitial nephritis and 1-25D overproduction in renal sarcoidosis, hypercalcemia secondary to elevation of 1-25D may be related to renal calcification and granuloma formation.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biopsy; Calcium; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Hypercalcemia; Kidney; Kidney Diseases; Macrophages; Male; Middle Aged; Nephritis, Interstitial; Retrospective Studies; Sarcoidosis; Steroids; Young Adult

Loss-of-function mutations of CYP24A1 (which encodes the 25-OH-D3-24-hydroxylase) have recently been reported to cause hypercalcemia.. The aims of this study were: 1) to evaluate the frequency of CYP24A1 mutations in patients with medical history of hypercalcemia; 2) to show the clinical utility of a simultaneous assay of serum 25-hydroxyvitamin D3 (25-OH-D3) and 24,25-dihydroxyvitamin D3 (24,25-[OH]2D3) by liquid chromatography tandem mass spectrometry (LC-MS/MS); and 3) to investigate biochemical parameters in heterozygous gene carriers with CYP24A1 mutations.. We screened for CYP24A1 mutations in 72 patients with serum calcium levels > 2.6 mmol/L and PTH levels < 20 pg/mL and recruited 24 relatives after genetic counseling for subsequent investigations. Vitamin D metabolite concentrations were assessed in a subset of patients by LC-MS/MS and results expressed as a ratio (R) of 25-OH-D3:24,25-(OH)2D3.. Twenty-five patients with hypercalcemia (35%) harbored CYP24A1 variations. Twenty (28%) had biallelic variations, mostly found in subjects with nephrocalcinosis or renal stones (19/20). Five patients, all neonates, were heterozygous, without renal disease. We describe 15 new variations leading to loss-of-function according to pathogenicity prediction programs, and we functionally characterized 5 of them in vitro. A dramatic increase of R, usually >80, was found in patients harboring biallelic mutations providing evidence in vivo for the loss of CYP24A1 activity. In contrast, R value remains <25 in patients without CYP24A1 mutations. Subjects carrying one mutant allele, hypercalcemic individuals, as well as gene-carrier relatives, had a detectable 24,25-(OH)2D3 level and R < 25, indicating normal 24-hydroxylase activity.. CYP24A1 biallelic mutations are frequently found in patients presenting with hypercalcemia, low PTH, and renal disease. We confirm the accuracy and effectiveness of a novel blood test estimating the ratio between relevant vitamin D metabolites as a useful screening tool for CYP24A1 mutations. Haploinsufficiency is not associated with CYP24A1 deficiency.

Topics: 24,25-Dihydroxyvitamin D 3; Adolescent; Adult; Aged; Aged, 80 and over; Calcium; Child; Child, Preschool; Chromatography, Liquid; Female; Humans; Hypercalcemia; Infant; Infant, Newborn; Male; Middle Aged; Mutation; Parathyroid Hormone; Tandem Mass Spectrometry; Vitamin D; Vitamin D3 24-Hydroxylase; Young Adult

The discovery of hypercalcemic diseases due to loss-of-function mutations in 25-hydroxyvitamin D-24-hydroxylase has placed a new demand for sensitive and precise assays for 24,25-dihydroxyvitamin D [24,25-(OH)2D].. We describe a novel liquid chromatography and tandem mass spectrometry-based method involving derivatization with DMEQ-TAD {4-[2-(6,7-dimethoxy-4-methyl-3,4-dihydroquinoxalinyl)ethyl]-1,2,4-triazoline-3,5-dione} to simultaneously assay multiple vitamin D metabolites including 25-hydroxyvitamin D (25-OH-D) and 24,25-(OH)2D using 100 μL of serum with a 5-minute run time.. The assay uses a newly synthesized internal standard d6-24,25-(OH)2D3 enabling the quantitation of 24,25-(OH)2D3 as well as the determination of the ratio of 25-OH-D3 to 24,25-(OH)2D3, a physiologically useful parameter.. We report data on more than 1000 normal and disease samples involving vitamin D deficiency or hypercalcemia in addition to studies involving knockout mouse models.. The assay showed good correlation with samples from quality assurance schemes for 25-OH-D (25-OH-D2 and 25-OH-D3) determination (-2% to -5% bias) and exhibited low inter- and intraassay coefficients of variation (4%-7%) and lower limits of quantitation of 0.25-0.45 nmol/L. In clinical studies, we found a strong correlation between serum levels of 25-OH-D3 and 24,25-(OH)2D3 (r(2) = 0.80) in subjects over a broad range of 25-OH-D3 values and a marked lack of production of 24,25-(OH)2D3 below 25 nmol/L of 25-OH-D. The ratio of 25-OH-D3 to 24,25-(OH)2D3, which remained less than 25 in vitamin D-sufficient subjects (serum 25-OH-D < 50 nmol/L) but was greatly elevated (80-100) in patients with idiopathic infantile hypercalcemia.. The new method showed good utility in clinical settings involving vitamin D deficiency; supplementation with vitamin D and idiopathic infantile hypercalcemia, as well as in animal models with ablation of selected cytochrome P450-containing enzymes involved in vitamin D metabolism.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Blood Chemical Analysis; Chromatography, Liquid; Dietary Supplements; Female; Humans; Hypercalcemia; Mice; Mice, Knockout; Predictive Value of Tests; Quinoxalines; Tandem Mass Spectrometry; Triazoles; Vitamin D; Vitamin D Deficiency

In patients with humoral hypercalcemia of malignancy (HHM), serum levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are generally low, although the pathophysiology of the impaired vitamin D metabolism is not fully understood. In the present study, we have investigated vitamin D metabolism in our newly developed rat model of HHM in which a human infantile fibrosarcoma producing parathyroid hormone-related protein (PTHrP), named OMC-1, was inoculated s.c. into athymic nude rats. In OMC-1-bearing rats, the serum concentration of 1,25(OH)(2)D was markedly reduced when the animals exhibited severe hypercalcemia (Ca > or =15 mg/dl), while it was rather elevated in those with mild hypercalcemia. To further examine whether serum Ca levels affect 1,25(OH)(2)D concentration, we administered bisphosphonate YM529 to OMC-1-bearing rats when they exhibited severe hypercalcemia. The restoration of the serum Ca level by administration of YM529 was accompanied by a marked increase in the 1,25(OH)(2)D level, suggesting that the serum Ca level itself plays an important role in the regulation of the 1,25(OH)(2)D level in these rats. On the other hand, when the OMC-1-bearing rats were treated with a neutralizing antibody against PTHrP, serum 1,25(OH)(2)D levels remained low despite the reduction in serum Ca levels. Expression of 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) in kidney was decreased in OMC-1-bearing rats with severe hypercalcemia, and markedly enhanced after treatment with bisphosphonate. This enhancement in 1 alpha-hydroxylase expression was not observed after treatment with the antibody against PTHrP. These results suggest that PTHrP was responsible for the enhanced expression of 1 alpha-hydroxylase in YM529-treated rats, and that hypercalcemia played a role in reducing the serum 1,25(OH)(2)D level in OMC-1-bearing rats by suppressing the PTHrP-induced expression of the 1 alpha-hydroxylase gene.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; Antibodies, Monoclonal; Blotting, Northern; Body Weight; Calcifediol; Calcitriol; Calcium; Calcium Channel Blockers; Diphosphonates; Fibrosarcoma; Gene Expression; Humans; Hypercalcemia; Imidazoles; Kidney; Male; Models, Animal; Neoplasm Transplantation; Parathyroid Hormone-Related Protein; Proteins; Rats; Rats, Nude; Reverse Transcriptase Polymerase Chain Reaction

We report on a 7-week-old infant with idiopathic hypercalcemia, hypercalciuria and nephrocalcinosis. At the time of admission, serum concentrations of parathyroid hormone and 1,25(OH)2D3 were found to be inadequately high, and those of calcitonin and 24,25(OH)2D3 too low, relative to the hypercalcemia. Treatment with calcitonin normalized serum calcium concentrations within 4 days, and a 3-week course of thiazides combined with a decreased dietary calcium:phosphorus ratio corrected the hypercalciuria. A repeat profile of the calcium-regulating hormones done at the age of 5.5 months was normal. Based on the clinical course and the hormonal profiles, we hypothesize that the idiopathic infantile hypercalcemia in this patient could have resulted from a generalized maturational delay of calcium homeostasis. Treatment with calcitonin, therefore, seems to be the most appropriate way to control the hypercalcemia.

Topics: 24,25-Dihydroxyvitamin D 3; Calcitonin; Calcitriol; Calcium; Female; Homeostasis; Humans; Hypercalcemia; Infant; Nephrocalcinosis; Parathyroid Hormone; Time Factors

We have examined the ability of blood-derived monocytes and macrophages isolated from a patient with alveolar rhabdomyosarcoma and hypercalcaemia, to form 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3). Adherent monocyte-macrophage cells incubated with 25(OH)D3 over the initial 2 days in culture synthesized 1.9 pmol 24,25(OH)2D3/h/incubation (representing 0.63 pmol/h/10(6) cells), whereas macrophages synthesized 1.03 and 1.15 pmol 1 alpha,25(OH)2D3/h/incubation after 1 and 4 weeks in culture respectively. In a further experiment synthesis of 1 alpha,25(OH)2D3 by long-term cultured macrophages fell from 2.25 to 0.04 pmol/h/incubation following exposure to 10 nM 1 alpha,25(OH)2D3 for 7 days, whereas 24,25(OH)2D3 synthesis was induced (0.46 pmol/h/incubation). The vitamin D3 metabolites were identified by co-chromatography with authentic 24,25(OH)2D3 or 1 alpha,25(OH)2D3 in three different high-performance liquid chromatography systems. Serum 1 alpha,25(OH)2D3 in the patient was markedly suppressed at 5 pg/ml (normal 20-50 pg/ml) indicating that raised 1 alpha,25(OH)2D3 was not the cause of the hypercalcaemia, but rather, that raised calcium may have suppressed renal 1 alpha,25(OH)2D3 synthesis. Administration of APD (3-amino-1-hydroxypropylidine-1,1-bisphosphonate) corrected the hypercalcaemia in the patient suggesting that increased bone resorption was responsible for the raised calcium. The results of this study show for the first time that immature blood derived monocyte-macrophage cells can synthesize 24,25(OH)2D3 before they mature into macrophages able to synthesize 1 alpha,25(OH)2D3.

Topics: 24,25-Dihydroxyvitamin D 3; Calcifediol; Calcitriol; Cells, Cultured; Chromatography, High Pressure Liquid; Humans; Hypercalcemia; Lung Neoplasms; Macrophages; Rhabdomyosarcoma

Seven patients with disordered calcium metabolism and high normal or elevated serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] were studied before and after the administration of 24,25-(OH)2D3 to determine its effects on calcium metabolism. Despite a significant increase in the mean serum 24,25-(OH)2D level [2.1 +/- 0.6 (+/- SE) to 16.7 +/- 6.2 nmol/L; P less than 0.05] after a daily dose of 20 micrograms for 1 month, there were no consistent changes in serum calcium, immunoreactive PTH, or 1,25-(OH)2D concentrations. Intestinal calcium absorption and urinary calcium excretion rose slightly during 24,25-(OH)2D administration in the majority of the patients. In the three patients in whom it was measured, serum 1,24,25-trihydroxyvitamin D levels did not change (19 +/- 5 vs. 20 +/- 5 pmol/L). We conclude that exogenous 24,25-(OH)2D3 at this dose has no significant antagonistic action on 1,25-(OH)2D and may have weak agonistic action.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Calcitriol; Calcium; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Female; Humans; Hypercalcemia; Hyperparathyroidism; Male; Middle Aged; Parathyroid Hormone

Circulating vitamin D metabolite concentrations, i.e. 25-(OH)D, 24,25-(OH)2D, 1,25-(OH)2D have been assayed in 14 hypercalcemic children. Results are as follows: a) Children with vitamin D intoxication (n = 2) had elevated serum 25-(OH)D and 24,25-(OH)2D concentrations but their 1,25-(OH)2D concentrations were similar to those found in normocalcemic children (10-110 pg/ml); b) Children with familial idiopathic hypercalcemia and hypocalciuria (n = 5), children with hypercalcemia and either Bartter's syndrome (n = 1), hemangiomatosis (n = 1), osteopetrosis after medullary graft (n = 1), also had 1,25-(OH)2D concentrations in the normal range; c) In contrast, 1,25-(OH)2D were elevated (160-470 pg/ml) in the four children with severe idiopathic hypercalcemia and elfin facies.

Topics: 24,25-Dihydroxyvitamin D 3; Calcifediol; Calcitriol; Calcium; Child, Preschool; Dihydroxycholecalciferols; Female; Humans; Hypercalcemia; Infant; Infant, Newborn; Male; Vitamin D

In order to investigate mineral and vitamin D metabolism in obese rats with hyperinsulinemia, plasma calcium and vitamin D metabolites were measured in Zucker fa/fa rats. Body weight, plasma insulin, and calcium in fa/fa rats were significantly increased compared to their lean littermates (p less than 0.01). However, no significant difference in plasma 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) or the ratio of 1,25(OH)2D to 25(OH)D was observed between fa/fa rats and their lean littermates. The hypercalcemia in the rats with hyperinsulinemia, therefore, might be caused by other calcium-regulating hormones or some factors other than 1,25(OH)2D. In addition, the hyperinsulinemia associated with obesity may not produce the accelerated conversion from 25(OH)D into 1,25(OH)2D.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Blood Glucose; Body Weight; Calcifediol; Calcitriol; Dihydroxycholecalciferols; Hypercalcemia; Hyperinsulinism; Male; Obesity; Rats; Rats, Zucker; Vitamin D

The effect of 24,25(OH)2D3 on 1,25(OH)2D3-induced hypercalcemia was studied in normal rats. Serum (S) levels and urinary excretion of Ca2+ (UCaV) were measured in (a) control rats, (b) rats receiving a daily sc injection of 54 ng 1,25(OH)2D3, (c) rats receiving 24,25(OH)2D3 in the same dose and same manner, and (d) rats receiving 1,25(OH)2D3 + 24,25(OH)2D3. The animals were housed in metabolic cages and 24-hr urine specimens were collected. After 24 hr SCa2+ increased similarly with 1,25(OH)2D3 and with 1,25(OH)2D3 + 24,25(OH)2D3, while 24,25(OH)2D3 alone did not change SCa2+. UCaV after 24 hr increased significantly less (P less than 0.025) with 1,25(OH)2D3 + 24,25(OH)2D3 than with 1,25(OH)2D3 alone. After 5 days of 1,25(OH)2D3, SCa2+ rose from 5.1 +/- 0.15 to 6.29 +/- 0.08 whereas 1,25(OH)2D3 + 24,25(OH)2D3 effected a greater increase in SCa2+ up to 6.63 +/- 0.09 (P less than 0.01). 24,25(OH)2D3 alone did not change SCa2+. UCaV after 5 days of treatment rose similarly with 1,25(OH)2D3 and with 1,25(OH)2D3 + 24,25(OH)2D3. After 10 days of 1,25(OH)2D3 SCa2+ was 6.17 +/- 0.15 meq/liter while with the combination SCa2+ rose to 6.74 +/- 0.2 (P less than 0.025). 24,25(OH)2D3 alone did not change SCa2+. These results show that (a) 24,25(OH)2D3 alone does not alter SCa2+ in normal rats, (b) combined administration of 1,25(OH)2D3 + 24,25(OH)2D3 enhances the hypercalcemic response to 1,25(OH)2D3 without a parallel increase in UCaV, and (c) it is suggested that the effect of 24,25(OH)2D3 on serum Ca2+ level, at least partly, may result from its hypocalciuric effect.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Bone and Bones; Calcitriol; Calcium; Dihydroxycholecalciferols; Drug Synergism; Hypercalcemia; Kidney Tubules; Male; Phosphates; Rats; Time Factors

Metabolites of vitamin D were measured in plasma from 83 patients with idiopathic infantile hypercalcaemia syndrome who were mentally handicapped but had normal calcium values at the time of the study. No significant difference was detected in the mean plasma concentrations of 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D3, or 25,26-dihydroxyvitamin D3 between patients and age matched controls. The mean plasma concentration of 25-hydroxyvitamin D3 was significantly lower in patients than controls but this may be a secondary phenomenon related to less sunlight exposure. In addition, two hypercalcaemic patients with this syndrome were studied during the first year of life, and were found to have normal concentrations of vitamin D metabolites. These findings do not support a role for abnormal vitamin D metabolism in the pathogenesis of this syndrome.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Adolescent; Calcitriol; Calcium; Child; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypercalcemia; Infant; Intellectual Disability; Male; Syndrome; Vitamin D

Three hypercalcemic renal transplant recipients with stable, excellent renal function (creatinine clearance 74 +/- 11.8 ml/min) were treated with 60 micrograms 24,25(OH)2D3 by mouth daily for three months. Immunoreactive c-terminal PTH, intact PTH, 1,25(OH)2D3, 25(OH)D3, 24,25(OH)2D3, and serum and 24 h urine calcium, phosphate, magnesium and creatinine were obtained before, at one week, one month and three months of treatment, and at six weeks post-treatment. Significant elevations in serum levels of 24,25(OH)2D3 were induced by therapy (1.32 +/- .16 ng/ml to 30.06 +/- 5.18 ng/ml at one month). Moderate elevations of c-terminal PTH and normal levels of intact PTH remained unchanged throughout the study. Serum calcium remained elevated, serum phosphate and magnesium remained depressed and creatinine clearance and urinary excretion of calcium, phosphate, and magnesium remained unchanged. Furthermore, 1,25(OH)2D3 and 25(OH)D3 remained in the normal range throughout the study. We conclude that 24,25(OH)2D3 did not have a suppressant effect on levels of iPTH in the clinical setting of persistent hyperparathyroidism after successful renal transplantation.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Calcium; Creatinine; Dihydroxycholecalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism; Kidney Transplantation; Magnesium; Male; Middle Aged; Parathyroid Hormone; Phosphates

The effects of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25-(OH)2D3) on parathyroid hormone (PTH) release from human parathyroid cells were investigated using an in vitro system of dispersed cells. The cells were obtained from 7 patients with primary hyperparathyroidism (HPT) and adenoma, 4 patients with primary HPT due to hyperplasia and 2 patients with parathyroid hyperplasia secondary to chronic renal failure. The dispersed cells were incubated in tissue culture medium at low, normal and high external calcium concentrations for 2-16 h. There was a gradual suppression of PTH release (5-55%) when the calcium concentration in the medium was increased from 0.5 to 3.0 mM, thus indicating retained regulation of hormone release. The addition of 1,25-(OH)2D3 in concentrations of 0.1 and 1 ng/ml and of 24,25-(OH)2D3 in concentrations of 1.0 and 10 ng/ml during the incubations did not further affect the amount of PTH released by the cells. The concentrations of the different vitamin D metabolites tested closely correspond to levels observed under normal physiological conditions and during treatment with high doses of vitamin D in vivo. Thus, the findings contradict the idea of any direct short-term regulatory effect of either 1,25-(OH)2D3 or 24,25-(OH)2D3 on the secretion of PTH from hyperfunctioning human parathyroid tissue.

Topics: 24,25-Dihydroxyvitamin D 3; Calcitriol; Calcium; Culture Media; Culture Techniques; Dihydroxycholecalciferols; Humans; Hypercalcemia; Hyperparathyroidism; Parathyroid Glands; Parathyroid Hormone; Time Factors

Serum vitamin D metabolites, the renal tubular maximum reabsorptive rate for phosphate (TMP/GFR) nephrogenic cyclic AMP (NcAMPI, and CaE (urinary calcium excretion per litre of glomerular filtrate) were measured in 14 adults with familial hypocalciuric hypercalcaemia (FHH). The findings were compared with analyses in 14 patients with surgically proven primary hyperparathyroidism matched for serum calcium, creatinine clearance and vitamin D status (assessed by serum concentrations of 25 hydroxyvitamin D). Vitamin D metabolites were also measured in 16 normocalcaemic relatives of patients with FHH. The serum concentration of 24,25 dihydroxycholecalciferol was appropriate for the prevailing 25 hydroxyvitamin D and no difference was found between groups. The serum concentration of 1,25 dihydroxycholecalciferol was significantly greater in primary hyperparathyroidism (P less than 0.0005) compared with patients with FHH and their normocalcaemic relatives. TMP/GFR was reduced in both primary hyperparathyroidism (0.53 +/- 0.12 mmol/l GF, mean +/- SEM) and FHH (0.86 +/- 0.14 mmol/l GF). Patients with primary hyperparathyroidism showed an increase in NcAMP output in the urine (38.5 +/- 16 mmol/l GF) which was significantly greater (P less than 0.0001) than the normal NcAMP (13.5 +/- 9.2 nmol/l GF) found in FHH. CaE was low in FHH indicating increased renal tubular reabsorption of calcium. It is concluded that there is no abnormality of vitamin D metabolism in FHH comparable with the changes observed in primary hyperparathyroidism. It is suggested that the biochemical abnormalities in FHH cannot be explained solely upon an increased sensitivity of the renal tubules to the effects of endogenous parathyroid hormone.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Calcitriol; Calcium; Cyclic AMP; Dihydroxycholecalciferols; Female; Humans; Hypercalcemia; Male; Parathyroid Glands; Parathyroid Hormone; Phosphates; Vitamin D

A 9-month-old boy who had the mild form of idiopathic infantile hypercalcemia was observed for 18 months. During the initial hypercalcemic stage, the serum concentration of 25-hydroxyvitamin D was normal. Urinary levels of cyclic adenosine monophosphate (cAMP) were low, and the serum concentrations of the dihydroxyl metabolites of vitamin D were appropriate to the high serum calcium concentration, with low 1,25-dihydroxyvitamin D and relatively high 24,25- and 25,26-dihydroxyvitamin D levels. Throughout the study period, there was a close positive correlation between the magnitude of the urinary cAMP excretion and the serum level of 1,25-dihydroxyvitamin D. The results indicate that excessive vitamin D intake leading to high serum levels of 25-hydroxyvitamin D are not decisive factors in the pathogenesis of idiopathic infantile hypercalcemia.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Calcitriol; Cyclic AMP; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hypercalcemia; Infant; Male; Phosphates; Phosphorus; Vitamin D