Determinants of the serum concentration of 1,25-dihydroxyvitamin D in primary hyperparathyroidism

1. The serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 44 patients with primary hyperparathyroidism. 2. In 14 patients the serum concentration of 1,25-dihydroxyvitamin D was greater than normal (142–337 pmol/l). One patient had a subnormal concentration of 1,25-dihydroxyvitamin D (36 pmol/l) but no other evidence of vitamin D deficiency. 3. The possible biological determinants of the serum concentration of 1,25-dihydroxyvitamin D were sought by multivariate analysis of relevant variables. The serum concentration of 1,25-dihydroxyvitamin D was found to be significantly and positively correlated with the serum concentrations of 25-hydroxyvitamin D (P < 0.001) and parathyroid hormone (P < 0.003), and with the glomerular filtration rate (P < 0.03), and negatively correlated with the serum concentrations of calcium (P < 0.02) and phosphate (P = 0.055) (multiple R = 0.638,P < 0.002). 4. In primary hyperparathyroidism the major determinant of serum 1,25-dihydroxyvitamin D is the availability of precursor 25-hydroxyvitamin D. 5. The finding that serum 1,25-dihydroxyvitamin D is commonly normal in patients with primary hyperparathyroidism despite an adequate state of vitamin D nutrition, can be explained in terms of the constraining influences of hypercalcaemia and variable degrees of renal dysfunction on the biosynthesis of 1,25-dihydroxyvitamin D.

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Influence of physical mobility and season on 25-hydroxyvitamin D-parathyroid hormone interaction and bone remodelling in the elderly

Acta Endocrinologica ◽

10.1530/eje.0.1430673 ◽

2000 ◽

pp. 673-679 ◽

Cited By ~ 21

Author(s):

R Theiler ◽

HB Stahelin ◽

M Kranzlin ◽

G Somorjai ◽

L Singer-Lindpaintner ◽

...

Keyword(s):

Vitamin D ◽

The Elderly ◽

Serum Concentrations ◽

Institutionalized Elderly ◽

Hydroxyvitamin D ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Physical Mobility ◽

25 Hydroxyvitamin D ◽

Mobility Status

OBJECTIVE: To investigate influences of physical mobility and season on 25-hydroxyvitamin D-intact parathyroid hormone (iPTH) interaction in the elderly. DESIGN: We examined 188 frail institutionalized elderly at the expected nadir of their serum vitamin D concentrations (winter). This group was compared with 309 healthy ambulatory elderly at the expected time of maximum vitamin D repletion (summer), to accentuate the influences of season and physical activity. METHODS: Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, iPTH and urinary deoxypyridinoline (DPD) were measured. RESULTS: Vitamin D metabolites were significantly lower in the institutionalized elderly (P<0.0001), with an 82.5% prevalence of vitamin D deficiency (25-hydroxyvitamin D <12ng/ml) in institutionalized elderly in wintertime and 15.5% in ambulatory elderly in summertime. Overall, median iPTH did not differ between groups. However, median iPTH secretion in the presence of low vitamin D serum concentrations (5-30ng/ml) was greater in ambulatory elderly. This could be explained by lower mobility status being correlated with greater serum calcium concentrations (r=0.24, P=0.02 in women; r=0.35, P=0. 001 in men) and greater urinary excretion of DPD (r=0.41, P=0.0001 in women; r=0.42, P=0.0002 in men), independent of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and iPTH. CONCLUSIONS: These data support the hypothesis that immobility, even in the presence of vitamin D deficiency, acts as an overriding influence on bone metabolism by promoting bone resorption (measured as urinary DPD) and increasing serum calcium independent of iPTH. Therefore mobility status may substantially affect 25-hydroxyvitamin D threshold values and the degree to which patients benefit from vitamin supplementation.

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Plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone in familial hypocalciuric hypercalcemia and primary hyperparathyroidism

Acta Endocrinologica ◽

10.1530/eje-08-0440 ◽

2008 ◽

Vol 159 (6) ◽

pp. 719-727 ◽

Cited By ~ 30

Author(s):

Signe Engkjær Christensen ◽

Peter H Nissen ◽

Peter Vestergaard ◽

Lene Heickendorff ◽

Lars Rejnmark ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Plasma Levels ◽

Familial Hypocalciuric Hypercalcemia ◽

Vitamin D Metabolism ◽

Hydroxyvitamin D ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

25 Hydroxyvitamin D

IntroductionFamilial hypocalciuric hypercalcemia (FHH) is a lifelong, benign, inherited condition caused by inactivating mutations in the calcium-sensing receptor (CASR) gene. Both FHH and primary hyperparathyroidism (PHPT) are characterized by elevated P-calcium, normal or elevated plasma-parathyroid hormone (P-PTH), and typically normal renal function. In PHPT, vitamin D metabolism is typically characterized by low plasma levels of 25-hydroxyvitamin D (25OHD), and high plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). In FHH, the vitamin D metabolism is not very well known.ObjectiveTo compare and evaluate plasma 25OHD, 1,25(OH)2D, and PTH in FHH and PHPT.DesignCross-sectional study.MaterialsAbout 66 FHH patients with mutations in the CASR gene, 147 patients with surgically verified PHPT, and 46 controls matched to FHH patients according to age (±5 years), sex, and season. All patients had a P-creatinine <140 μmol/l.MethodsWe measured P-calcium, P-Ca2+, P-albumin, P-creatinine, P-phosphate, P-magnesium, and P-PTH by standard laboratory methods. P-25OHD and P-1,25(OH)2D were measured by RIA or enzyme immunoassay. In FHH, all protein-coding exons in the CASR gene were sequenced and aligned to GenBank reference sequence .ResultsPHPT patients had higher body mass index (2p<0.01), together with higher P-PTH (2p<0.01) and P-1,25(OH)2D (2p<0.01) compared with FHH patients. The groups had similar levels of P-Ca2+ and of P-25OHD. The phenotypic expression of the CASR mutations (as determined by the degree of hypercalcemia) did not influence the levels of P-1,25(OH)2D.ConclusionEven though P-calcium and P-25OHD were comparable, P-1,25(OH)2D and P-PTH differed between FHH and PHPT.

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

Canadian Journal of Zoology ◽

10.1139/z87-323 ◽

1987 ◽

Vol 65 (8) ◽

pp. 2111-2112 ◽

Cited By ~ 4

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.

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

Clinical Science ◽

10.1042/cs0860627 ◽

1994 ◽

Vol 86 (5) ◽

pp. 627-632 ◽

Cited By ~ 3

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.

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

Journal of International Medical Research ◽

10.1177/030006058901700305 ◽

1989 ◽

Vol 17 (3) ◽

pp. 226-242 ◽

Cited By ~ 9

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.

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

PEDIATRICS ◽

10.1542/peds.71.1.59 ◽

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.

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

PEDIATRICS ◽

10.1542/peds.80.1.97 ◽

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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Familial hypocalciuric hypercalcaemia: observations on vitamin D metabolism and parathyroid function

Acta Endocrinologica ◽

10.1530/acta.0.1040210 ◽

1983 ◽

Vol 104 (2) ◽

pp. 210-215 ◽

Cited By ~ 16

Author(s):

M. Davies ◽

P. H. Adams ◽

J. L. Berry ◽

G. A. Lumb ◽

P. S. Klimiuk ◽

...

Keyword(s):

Vitamin D ◽

Serum Concentration ◽

Primary Hyperparathyroidism ◽

Calcium Excretion ◽

Renal Tubules ◽

Vitamin D Metabolites ◽

Vitamin D Metabolism ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Renal Tubular

Abstract. 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 < 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 < 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.

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Simultaneous determination of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D in plasma or serum.

Clinical Chemistry ◽

10.1093/clinchem/27.10.1757 ◽

1981 ◽

Vol 27 (10) ◽

pp. 1757-1760 ◽

Cited By ~ 17

Author(s):

M J Jongen ◽

W J van der Vijgh ◽

H J Willems ◽

J C Netelenbos ◽

P Lips

Keyword(s):

Vitamin D ◽

Vitamin D Metabolites ◽

Binding Assays ◽

Hydroxyvitamin D ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Extraction And Purification ◽

Chromatographic Procedure ◽

25 Hydroxyvitamin D ◽

Liquid Chromatographic

Abstract We describe a simultaneous assay for the principal vitamin D metabolites: 25-hydroxyvitamin D, 24-25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D. Special attention has been paid to simplification of the extensive extraction and purification procedures used in previously described simultaneous assays. All three metabolites were isolated with a single extraction step, followed by only one gradient liquid-chromatographic procedure. For final quantitation we used competitive protein binding assays, involving readily available binding proteins and commercially purchased tritiated vitamin D metabolites. Concentrations in the plasma of healthy subjects (mean age, 27 years), sampled during December were 51 (SD 17) nmol/L, 4.1 (SD 1.3) nmol/L, and 124 (SD 26) pmol/L for 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D, respectively. Intra- and interassay CVs for the three metabolites were 4.4 and 3.9%, 6.7 and 8.0%, and 7.0 and 4.8%, respectively.

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