Extrarenal synthesis of 1,25-dihydroxyvitamin D: Sensitivity to glucocorticoid treatment

1987 ◽  
Vol 72 (3) ◽  
pp. 329-334 ◽  
Author(s):  
Silvano Adami ◽  
G. Graziani ◽  
D. Tartarotti ◽  
R. Cappelli ◽  
S. Casati ◽  
...  
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Glucocorticoid Treatment ◽  
Prednisone Therapy ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Prednisone Treatment ◽  
Vitamin D Intoxication ◽  
Before And After

1. The response of circulating 1,25-dihydroxyvitamin D [l,25-(OH)2D] to challenge with vitamin D treatment both before and after 7–10 days of prednisone therapy (25 mg/day) was investigated in five anephric subjects, six patients with chronic renal failure (CRF), two patients with vitamin D intoxication and four patients with hypoparathyroidism. 2. In anephric subjects serum 25-hydroxyvitamin D [25-(OH)D] rose from 58 ± 48 (sd) to 377±221 (sd) nmol/l after administration of 150 μg of 25-(OH)D3 for 1 month. Serum l,25-(OH)2D, which was barely detectable in only two out of five patients under basal conditions, rose to 30 ± 21 pmol/l after 2 weeks of therapy with 25-(OH)D3, but fell to 10 ± 5 pmol/l during prednisone treatment. 3. In CRF patients circulating l,25-(OH)2D rose from 37 ± 24 to 58 ± 24 pmol/l during 25-(OH)D3 therapy, but fell to 41 ± 31 pmol/l during prednisone treatment. In two patients with rheumatoid arthritis, hypercalcaemia due to vitamin D intoxication was associated with raised levels of 1,25-(OH)2D (288 and 317 pmol/l). Administration of prednisore resulted in suppression of l,25-(OH)2D levels (132 and 96 pmol/l respectively) and reduction of serum calcium to within the normal range. 4. In the hypoparathyroid patients prednisone therapy did not affect circulating 25-(OH)D levels but serum l,25-(OH)2D fell from 192 ± 42 to 117 ± 23 pmol/l and serum calcium from 2.41 ± 0.21 to 2.20 ± 0.05 mmol/l. 5. These findings indicate that a steroid sensitive extrarenal production of l,25-(OH)2D may occur in all subjects with a threshold serum concentration of the precursor 25-(OH)D.

Responses of serum calcium and phosphorus in the frog Rana tigrina to injection of various vitamin D analogs

1987 ◽  
Vol 65 (8) ◽  
pp. 2111-2112 ◽  
Author(s):  
Ajai K. Srivastav ◽  
L. Rani ◽  
K. Swarup
Keyword(s):  
Vitamin D ◽  
Serum Calcium ◽  
Vitamin D Analogs ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Rana Tigrina ◽  
Calcium Deposits ◽  
25 Hydroxyvitamin D ◽  
Calcium And Phosphorus

Intraperitoneal injections of either vitamin D3 (4 IU/100 g body wt.), 25 hydroxyvitamin D3 (100 ng/100 g body wt.), or 1,25 dihydroxyvitamin D3 (100 ng/100 g body wt.) for 15 days induced hypercalcemia, hyperphosphatemia, and depletion of calcium deposits in the paravertebral lime sacs in an anuran, Rana tigrina.

A simplified assay for dihydroxylated vitamin D metabolites in human serum: application to hyper- and hypovitaminosis D.

1980 ◽  
Vol 26 (3) ◽  
pp. 444-450 ◽  
Author(s):  
R S Mason ◽  
D Lissner ◽  
H S Grunstein ◽  
S Posen
Keyword(s):  
Vitamin D ◽  
Human Serum ◽  
Hypovitaminosis D ◽  
Reference Interval ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Vitamin D Intoxication ◽  
25 Hydroxyvitamin D

Abstract We describe a simplified assay for 24,25-and 1.25-dihydroxyvitamin D in human serum. It involves two preparative steps, and normal chick intestine is used in preparing cytosol-binding protein. Our results for 24,25-dihydroxyvitamin D include a reference interval of 2.9—16 nmol/L (1.2—6.7 microgram/L), a mean of 6.7 nmol/L (2.8 microgram/L), an intra-assay CV of 11%, and an interassay CV of 22%. For 1,25-dihydroxyvitamin D, these data were 29—168 pmol/L (12—70 ng/L), 86 pmol/L (36 ng/L), 12%, and 22%, respectively. In hypoparathyroid patients with vitamin D intoxication, mean concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum were significantly above normal; the 1,25-dihydroxyvitamin D concentrations were significantly below normal. Patients with malabsorption and/or post-gastrectomy states had significantly subnormal values for both 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum, and there was a significantly negative correlation between each of these biochemical values and the severity of osteomalacia. We also discuss cost effectiveness of assaying vitamin D metabolites in human serum.

A simplified assay for dihydroxylated vitamin D metabolites in human serum: application to hyper- and hypovitaminosis D.

1980 ◽  
Vol 26 (3) ◽  
pp. 444-450 ◽  
Author(s):  
R S Mason ◽  
D Lissner ◽  
H S Grunstein ◽  
S Posen
Keyword(s):  
Vitamin D ◽  
Human Serum ◽  
Hypovitaminosis D ◽  
Reference Interval ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Vitamin D Intoxication ◽  
25 Hydroxyvitamin D

Abstract We describe a simplified assay for 24,25-and 1.25-dihydroxyvitamin D in human serum. It involves two preparative steps, and normal chick intestine is used in preparing cytosol-binding protein. Our results for 24,25-dihydroxyvitamin D include a reference interval of 2.9—16 nmol/L (1.2—6.7 microgram/L), a mean of 6.7 nmol/L (2.8 microgram/L), an intra-assay CV of 11%, and an interassay CV of 22%. For 1,25-dihydroxyvitamin D, these data were 29—168 pmol/L (12—70 ng/L), 86 pmol/L (36 ng/L), 12%, and 22%, respectively. In hypoparathyroid patients with vitamin D intoxication, mean concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum were significantly above normal; the 1,25-dihydroxyvitamin D concentrations were significantly below normal. Patients with malabsorption and/or post-gastrectomy states had significantly subnormal values for both 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum, and there was a significantly negative correlation between each of these biochemical values and the severity of osteomalacia. We also discuss cost effectiveness of assaying vitamin D metabolites in human serum.

Calcium Malabsorption in Elderly Women with Vertebral Fractures: Evidence for Resistance to the Action of Vitamin D Metabolites on the Bowel

1984 ◽  
Vol 66 (1) ◽  
pp. 103-107 ◽  
Author(s):  
R. M. Francis ◽  
M. Peacock ◽  
G. A. Taylor ◽  
J. H. Storer ◽  
B. E. C. Nordin
Keyword(s):  
Vitamin D ◽  
Vertebral Fractures ◽  
Calcium Absorption ◽  
Elderly Women ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Significant Difference ◽  
Before And After ◽  
Calcium Malabsorption

1. Radio-calcium absorption, plasma 25-hydroxyvitamin D [25-(OH)D] and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were measured in 19 elderly women with, and 21 without, vertebral fractures, before and after treatment with 25-hydroxyvitamin D3 [25-(OH)D3], to establish whether malabsorption of calcium in elderly women with vertebral fractures has a cause different from that in elderly women without vertebral fractures. 2. Malabsorption of calcium and low plasma 25-(OH)D and 1,25-(OH)2D concentrations were common in both groups of women but there was no significant difference in these variables between the two groups. 3. After treatment with 40 μg of 25-(OH)D3 daily for 7 days, there was a significant increase in plasma 25-(OH)D and 1,25-(OH)2D in both groups of women, but radio-calcium absorption increased significantly only in the group without vertebral fractures. 4. Elderly women with vertebral fractures have malabsorption of calcium which is resistant to the action of vitamin D metabolites at concentrations which correct calcium malabsorption in elderly women without vertebral fractures.

Cyclosporin a and Vitamin D Metabolism: Studies in Patients with Psoriasis and in Rats

1994 ◽  
Vol 86 (5) ◽  
pp. 627-632 ◽  
Author(s):  
A. J. Shaw ◽  
M. E. Hayes ◽  
M. Davies ◽  
B. D. Edwards ◽  
F. W. Ballardie ◽  
...  
Keyword(s):  
Vitamin D ◽  
Synovial Fluid ◽  
Cyclosporin A ◽  
Severity Index ◽  
Hydroxylase Activity ◽  
Local Synthesis ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

1. Cyclosporin A, an immunosuppressive drug used to treat psoriasis, stimulates renal synthesis of 1,25-dihydroxyvitamin D in rats. 1,25-Dihydroxy vitamin D can also reduce the activity of psoriasis, and in the present study we have examined the possibility that cyclosporin A mediates some of its actions in psoriasis by renal or extra-renal production of 1,25-dihydroxyvitamin D. 2. Treatment of 12 psoriatic patients with cyclosporin A (5 mg day−1 kg−1) for 3 months significantly improved the psoriasis activity and severity index and reduced glomerular filtration rate, but serum 1,25-dihydroxyvitamin D levels were not changed. However, 1–3 months after stopping cyclosporin A treatment, an increase in the psoriasis activity and severity index score was accompanied by a small, but significant, increase in serum 1,25-dihydroxyvitamin D concentration. Plasma 1,25-dihydroxyvitamin D levels in rats gavaged with cyclosporin A (15 mg day−1 kg−1 for 2 weeks) were significantly increased compared with controls, but a lower dose of cyclosporin A (2.4 mg day−1 kg−1) had no effect. Renal 25-hydroxyvitamin D-24-hydroxylase activity in rat kidney homogenates was not different between control and cyclosporin A-treated rats. Renal 25-hydroxyvitamin D-1α-hydroxylase activity was not detectable in these homogenates. Extra-renal production of 1,25-dihydroxyvitamin D by activated macrophages isolated from the synovial fluid of patients with inflammatory arthritis was reduced after incubation with cyclosporin A (0.1–10 μmol/l) for 30 h or 5 days. 3. It is unlikely that alteration of circulating 1,25-dihydroxyvitamin D concentration is one of the modes of action of cyclosporin A in psoriasis. Since cyclosporin A inhibits 1,25-dihydroxyvitamin D production by activated synovial fluid macrophages, it is unlikely that cyclosporin A mediates some of its therapeutic actions by local synthesis of 1,25-dihydroxyvitamin D within the psoriatic lesion.

1α,25-dihydroxyvitamin D3 corrects osteomalacia in hypoparathyroidism and pseudohypoparathyroidism

1983 ◽  
Vol 103 (2) ◽  
pp. 241-247 ◽  
Author(s):  
Sol Epstein ◽  
Pierre J. Meunier ◽  
Phillip W. Lambert ◽  
Paula H. Stern ◽  
Norman H. Bell
Keyword(s):  
Serum Calcium ◽  
Inorganic Phosphate ◽  
Binding Assay ◽  
Bone Biopsy ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Before And After ◽  
25 Hydroxyvitamin D ◽  
Serum Inorganic Phosphate

Abstract. Deficiency of circulating 1α,25-dihydroxyvitamin D (1α,25(OH)2D) regularly occurs in hypoparathyroidism (HP) and pseudohypoparathyroidism (PHP). Osteomalacia is occasionally found in the two diseases. Two patients, one with HP and the other with PHP, both with symptomatic and biopsy-proven osteomalacia, were studied before and after treatment with 1α,25(OH)2D3. Laboratory values before treatment were as follows: serum immunoreactive parathyroid hormone was undetectable in the patient with HP and was elevated in the patient with PHP. Serum 25-hydroxyvitamin D, measured by binding assay, was 131.5 and 61.9 nmol/l (normal: 69.1 ± 15.9 nmol/l); serum 24,25-dihydroxyvitamin D, measured by binding assay, was 13.9 and 3.8 nmol/l (normal: 3.4 ± 1.4 nmol/l); serum 1α,25(OH)2D, measured by bioassay, was 28.6 and 29.0 pmol/l (normal: 77.3 ± 22.8 pmol/l) and, measured by receptor assay, was 36.2 and 41.0 pmol/l (normal: 71.8 ± 35.8 pmol/l) in the HP and PHP patients, respectively. Serum calcium was low and serum inorganic phosphate was high in both cases. Treatment with 1α,25(OH)2D3 (3–5 μg per day for 10–12 months) restored serum calcium and inorganic phosphate to normal, alleviated bone pain and healed the osteomalacia as shown on repeat bone biopsy. Our results provide further evidence that isolated deficiency of 1α,25(OH)2D may cause osteomalacia or rickets.

Vitamin D and Calcitonin Treatment in Patients with Femoral Neck Fracture: A Prospective Controlled Clinical Study

1989 ◽  
Vol 17 (3) ◽  
pp. 226-242 ◽  
Author(s):  
E. Harju ◽  
R. Punnonen ◽  
R. Tuimala ◽  
J. Salmi ◽  
I. Paronen
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Serum Levels ◽  
Serum Calcitonin ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Age Related ◽  
Neck Fracture ◽  
25 Hydroxyvitamin D

The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9) and 25 μg calcitonin given subcutaneously 30 times ( n=10) in 10 weeks were studied against a control ( n=ll). Bone histology and histomorphometry showed non-age related osteoporosis in 30% and osteomalacia in 22% of the patients studied. Impaired serum vitamin D status was found in 47 – 88% of patients, secondary hyperparathyroidism and increased serum parathyroid hormone in 59% and decreased serum calcitonin levels in 69%. On histology, normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3. Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia. Calcitonin improved calcium balance, reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia. Vitamin D reduced osteomalacia, slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone. Both treatments gave a similar slight decrease in serum calcitonin concentrations. A mechanism of action for the treatments is suggested.

Effect of Parathyroid Hormone on cAMP and 1,25-Dihydroxyvitamin D Formation and Renal Handling of Phosphate in Vitamin D-Dependent Rickets

PEDIATRICS ◽  
1983 ◽  
Vol 71 (1) ◽  
pp. 59-63
Author(s):  
Dagfinn Aarskog ◽  
Lage Aksnes ◽  
Trond Markestad
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Serum Concentration ◽  
Urinary Excretion ◽  
Serum Levels ◽  
Renal Handling ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Control Subjects

Studies were carried out to compare the effects of parathyroid extract (PTE) on the serum concentration of 1,25-dihydroxyvitamin D (1,25[OH]2D), 24,25-dihydroxyvitamin D (24,25[OH]2D), 25,26-dihydroxy vitamin D (25,26[OH]2D) and cAMP, and the urinary excretion of calcium, phosphorus, and cAMP in two normal adult subjects, and in a girl with vitamin D-dependent rickets. The concentration of 1,25[OH]2D was markedly decreased even when she was receiving a daily dose of 25,000 IU of ergocalciferol. PTE infusion resulted in a prompt and distinct increase in the serum levels and the urinary excretion of cAMP in the patient and control subjects. In the control subjects the serum concentration of 1,25[OH]2D increased after the PTE infusion, whereas there was no response in the patient with vitamin D-dependent rickets. The two other dihydroxylated metabolites of vitamin D showed no consistent response to the PTE infusion in the control subjects or the patient. The patient showed no phosphaturic response to PTE while she was receiving high-dosage ergocalciferol treatment. By contrast, when the patient was re-studied after therapy with lα-hydroxyvitamin D, PTE infusion resulted in an increase in urinary phosphate excretion. These findings might lend support for the notion that 1,25[OH]2D has an effect on tubular phosphate resorption and has a permissive role in the phosphaturic effect of parathyroid hormone. The present findings also confirm that the formation of 1,25[OH]2D is impaired in vitamin D-dependent rickets and indicate that the renal 25-hydroxyvitamin D-lα-hydroxylase is unresponsive to the stimulatory effect of parathyroid hormone in this condition.

1α-Hydroxyvitamin D3 Treatment of Three Patients With 1,25-Dihydroxyvitamin D-Receptor-Defect Rickets and Alopecia

PEDIATRICS ◽  
1987 ◽  
Vol 80 (1) ◽  
pp. 97-101
Author(s):  
E. Takeda ◽  
Y. Kuroda ◽  
T. Saijo ◽  
E. Naito ◽  
H. Kobashi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Lactate ◽  
Type Ii ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

Three patients with clinically different severities of vitamin D-dependent rickets, type II, with alopecia, which is 1,25-dihydroxyvitamin D-receptor-defect rickets and is particularly resistant to treatment with calciferol analogues, were treated with large doses of lα-hydroxyvitamin D3 (1α-(OH)D3) and 2 g of calcium lactate. Except for the alopecia, all of the abnormalities of patients 1 and 2 were reversed by treatment with 3 µg/kg/d of 1α-(OH)D3, and those of patient 3, who had the severest manifestations, were reversed by treatment with 6 µg/kg/d. The serum 24,25-dihydroxyvitamin D concentrations of the three patients were low before treatment and those of patients 1 and 2 increased during treatment. These findings suggest that in patients 1 and 2, 25-hydroxyvitamin D-24-hydroxylase was stimulated via a 1,25-dihydroxyvitamin D-receptor-mediated system by treatment with 1α-(OH)D3.

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