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

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

Clinical Science ◽

10.1042/cs0760081 ◽

1989 ◽

Vol 76 (1) ◽

pp. 81-86 ◽

Cited By ~ 16

Author(s):

B. C. Lalor ◽

E. B. Mawer ◽

M. Davies ◽

G. A. Lumb ◽

L. Hunt ◽

...

Keyword(s):

Vitamin D ◽

Serum Concentration ◽

Primary Hyperparathyroidism ◽

Serum Concentrations ◽

Hydroxyvitamin D ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Relevant Variables ◽

Biological Determinants ◽

25 Hydroxyvitamin D

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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Vitamin D Status and Indices of Mineral Homeostasis in the Population: Differences Between 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D

Nutrients ◽

10.3390/nu11081777 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1777 ◽

Cited By ~ 4

Author(s):

Massimo Cirillo ◽

Giancarlo Bilancio ◽

Ermanno Guarino ◽

Pierpaolo Cavallo ◽

Cinzia Lombardi ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Study Cohort ◽

Urine Calcium ◽

Hydroxyvitamin D ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Mineral Homeostasis ◽

25 Hydroxyvitamin D ◽

Serum And Urine

Opinions are conflicting about the epidemiology of vitamin D deficiency. This population-based study investigated cross-sectionally the associations of 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol) with indices of mineral homeostasis. Study cohort consisted of 979 persons of the Moli-Sani study, both sexes, ages ≥35 years. Data collection included serum calcidiol by different assays, serum calcitriol, serum parathyroid hormone, serum and urine calcium, and phosphorus. Prevalence of mild-to-moderate calcidiol deficiency (10–19 ng/mL) was 36.4% and did not associate with hypocalcemia or hyperparathyroidism. Prevalence of severe calcidiol deficiency (<10 ng/mL) was 16.8% and associated with hyperparathyroidism only (odds ratio = 8.81, 95% confidence interval = 2.4/32.9). Prevalence of calcitriol deficiency (<18 pg/mL) was 3.1% and associated with hypocalcemia (29.1, 7.4/114.5) but not hyperparathyroidism. In ANOVA along concentration strata, lower calcidiol associated with higher parathyroid hormone only (p < 0.001). Lower calcitriol associated with lower serum and urine calcium (p < 0.001) but not with parathyroid hormone. Calcidiol findings were consistent with different calcidiol assays. In the population, mild-to-moderate calcidiol deficiency did not associate with abnormal mineral homeostasis. Severe calcidiol deficiency and calcitriol deficiency associated with different disorders: lower calcidiol associated with hyperparathyroidism whereas lower calcitriol associated with hypocalcemia and low urine calcium.

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Abnormal parathyroid hormone stimulation of 25-hydroxyvitamin D-1 alpha-hydroxylase activity in the hypophosphatemic mouse. Evidence for a generalized defect of vitamin D metabolism.

Journal of Clinical Investigation ◽

10.1172/jci112274 ◽

1986 ◽

Vol 77 (1) ◽

pp. 181-187 ◽

Cited By ~ 51

Author(s):

T Nesbitt ◽

M K Drezner ◽

B Lobaugh

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Hydroxylase Activity ◽

Vitamin D Metabolism ◽

Hormone Stimulation ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Stimulation Of

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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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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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Assay-Specific Decision Limits for Two New Automated Parathyroid Hormone and 25-Hydroxyvitamin D Assays

Clinical Chemistry ◽

10.1373/clinchem.2004.037606 ◽

2005 ◽

Vol 51 (2) ◽

pp. 395-400 ◽

Cited By ~ 37

Author(s):

Jean-Claude Souberbielle ◽

Véronique Fayol ◽

Corinne Sault ◽

Ethel Lawson-Body ◽

André Kahan ◽

...

Keyword(s):

Vitamin D ◽

Regression Analysis ◽

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Healthy Individuals ◽

Hydroxyvitamin D ◽

Low Concentrations ◽

25 Hydroxyvitamin D ◽

High Concentrations ◽

Serum Pth

Abstract Background: The recent development of nonradioactive automated assays for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) has made measurement of these two hormones possible in many laboratories. In this study, we compared two new assays for PTH and 25OHD adapted on an automated analyzer, the LIAISON®, with two manual immunoassays used worldwide. Methods: We studied 228 osteoporotic patients, 927 healthy individuals, 38 patients with primary hyperparathyroidism, and 167 hemodialyzed patients. Serum PTH was measured with the Allegro® and the LIAISON assays, and 25OHD was measured with DiaSorin RIA and the LIAISON assay. Regression analysis was used to calculate decision thresholds for the LIAISON assays that were equivalent to those of the Allegro PTH and DiaSorin 25OHD assays. Results: The 25OHD concentrations obtained with the LIAISON assay and the RIA in osteoporotic patients were well correlated (r = 0.83; P <0.001). Regression and Bland–Altman analyses suggested that the LIAISON 25OHD assay reads lower than the DiaSorin RIA at low concentrations but higher at high concentrations. However, the cutoff (50 nmol/L) used in our laboratories to define vitamin D insufficiency with the DiaSorin RIA is applicable to the LIAISON 25OHD assay. In 927 healthy individuals, the 3rd–97th percentile intervals were 3–80 ng/L and 13–151 nmol/L for the LIAISON PTH and 25OHD concentrations, respectively. However, 506 individuals (54.6%) were vitamin D-insufficient; we therefore considered only the 421 individuals with a LIAISON 25OHD >50 nmol/L as eligible for the reference population for the LIAISON PTH assay. In this group, the 3rd–97th percentile interval for LIAISON PTH was 3–51 ng/L. Considering upper reference limits of 46 and 51 ng/L for the Allegro and LIAISON assays, respectively, the frequency of above-normal PTH concentrations in patients with primary hyperparathyroidism was similar in both assays. Regression analysis between serum PTH measured by the Allegro and LIAISON assays in 167 hemodialyzed patients and the corresponding Bland–Altman analysis of these data suggest that the LIAISON PTH assay tends to read higher than the Allegro assay at low concentrations but lower at high concentrations (>300 ng/L). Conclusions: Because clinical decision limits for both PTH and 25OHD should be assay specific, we propose equivalences between these assays and two manual assays used worldwide. These assay-specific decision limits should help potential users of the LIAISON PTH and 25OHD assays.

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