25-hydroxyvitamin-d-2 and Hypoparathyroidism

Topics: 25-Hydroxyvitamin D 2; Animals; Calcifediol; Calcitriol; Calcium; Cyclic AMP; Ergocalciferols; Glomerular Filtration Rate; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Hypoparathyroidism; Mathematics; Methods; Parathyroid Diseases; Parathyroid Hormone

In 23 patients with hypoparathyroidism or pseudohypoparathyroidism treated with vitamin D, and in whom the dosage was adjusted downward or upward in response to hypercalcemia or hypocalcemia respectively, assays of serum 25-hydroxyvitamin D (25-OHD) were carried out in addition to the usual serum calcium assays. In 120 assays there was a significant correlation between serum 25-OHD levels and serum calcium levels (corrected for serum albumin). There was, however, no clear distinction between the 25-OHD levels of patients who were hypocalcemic, normocalcemic or hypercalcemic. The highest serum 25-OHD level found in a hypocalcemic patient was 1193 nmol/L and the lowest serum 25-OHD level found in a hypercalcemic patient was 605 nmol/L. It was not possible to predict subsequent episodes of hypocalcemia or hypercalcemia from the serum 25-OHD levels. The 25-OHD assay was found to be useful only in checking compliance. We conclude that the assay of serum 25-OHD is of no more value than serum calcium alone in the management of compliant patients.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Calcium; Ergocalciferols; Female; Humans; Hypoparathyroidism; Male; Middle Aged; Pseudohypoparathyroidism

This interlaboratory study on determination of 25-hydroxyvitamin D (25-OH-D) in serum involved 15 laboratories in eight European countries. All could distinguish between normal (50 +/- 31 nmol/L, mean +/- SD) and grossly increased concentrations, but for eight laboratories the results for serum samples with low and normal 25-OH-D content overlapped. In general, values were well reproducible, but interlaboratory variation in 25-OH-D measurement was large, 24,25(OH)2D3 interfering in most of the assays. We present evidence in favor of chromatography before assay, as opposed to nonchromatographic methods. Liquid chromatography with ultraviolet detection for quantifying 25-OH-D2 and 25-OH-D3 appears to be an appropriate reference method, whereas competitive protein binding assay is the method of choice for routine determinations. Control sera with subnormal, normal, and above-normal concentrations of 25-OH-D3 are needed for use in standardization of 25-OH-D assays.

Topics: 25-Hydroxyvitamin D 2; Calcifediol; Carrier Proteins; Charcoal; Chemistry, Clinical; Cholecalciferol; Chromatography, High Pressure Liquid; Ergocalciferols; Europe; False Positive Reactions; Humans; Hypoparathyroidism; Spectrophotometry, Ultraviolet; Vitamin D; Vitamin D-Binding Protein

A sensitive radioimmunoassay for 1,25-dihydroxy vitamin D2 was developed using a sheep antiserum which preferentially reacts with 1-hydroxylated forms of vitamin D. An improved isolation procedure was also developed using acetonitrile for the initial extraction of serum followed by chromatography on cartridges of C18 silica and high pressure liquid chromatography eluted with a ternary solvent system to separate 1,25-dihydroxy vitamin D2 and 1,25-dihydroxy vitamin D3. 25-hydroxy vitamin D2 and 25-hydroxy vitamin D3 were separated by further reverse phase high pressure liquid chromatography prior to competitive protein binding assay. The limits of detection were 4.3 pmol/1 (2.0 pg/ml) for the 1,25-dihydroxy metabolites and 1.25 nmol/1 (0.5 ng/ml) for both 25-hydroxy vitamin D2 and 25-hydroxy vitamin D3. 25-hydroxy vitamin D2 ranged from 2.0 to 11.3 nmol/1 (0.8-4.5 ng/ml) with a mean of 4.75 nmol/1 (1.9 ng/ml) in thirteen healthy British adults and this accounted for 9.0% of the mean total 25-hydroxy vitamin D. 1,25-dihydroxy vitamin D2 was detected in the sera of only one of these subjects whereas 1,25-dihydroxy vitamin D3 was present in all ranging from 48 to 163 pmol/1 (20-65 pg/ml) with a mean of 100 pmol/1 (42 pg/ml). Both 1,25-dihydroxy vitamin D2 and 1,25-dihydroxy vitamin D3 were detected in the sera of hypoparathyroid patients treated with vitamin D2 but the relationship between 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D was complex. For example, when an excess of 25-hydroxy vitamin D2 was present the serum concentration of 1,25-dihydroxy vitamin D3 was disproportionately high. Conversely, in patients who had previously been treated with vitamin D2 but were receiving only vitamin D3 at the time of study, the major 25-hydroxy metabolite was in the vitamin D3 form and there was a disproportionately high amount of 1,25-dihydroxy vitamin D2. Total 1,25-dihydroxy vitamin D ranged from 110 to 400 pmol/1 (45-165 pg/ml) and was above the upper limit of normal for 1,25-dihydroxy vitamin D3 in half of these hypoparathyroid patients treated with pharmacological doses of vitamin D.

Topics: 25-Hydroxyvitamin D 2; Calcifediol; Calcitriol; Chromatography, High Pressure Liquid; Ergocalciferols; Humans; Hydroxylation; Hypoparathyroidism; Radioimmunoassay

A 17-year-old girl with thalassemia major experienced tetany. The serum calcium level was 5.5 mg/dL, and the phosphorus level was 6.3 mg/dL. Serum levels of parathyroid hormone (PTH) and 25-hydroxyvitamin D (25-OHD) were subnormal at 125 pg/mL and 8.1 ng/mL, respectively, As a result of these findings, serum 25-OHD and PTH levels were measured in an additional 12 patients with thalassemia major. Low levels of both 25-OHD and PTH were found frequently. An increase in serum 25-OHD levels was noted in each of four patients who were examined after iron chelation therapy.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Child; Deferoxamine; Ergocalciferols; Female; Humans; Hypoparathyroidism; Male; Thalassemia

Serum calcium, phosphorus, calcitonin, parathyroid hormone, 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] were measured in 6 women and 2 men with medullary carcinoma of the thyroid, 22 normal subjects, 5 patients with chronic renal failure, and 5 patients with primary hyperparathyroidism. Serum 1,25-(OH)2D levels were significantly higher in patients with primary hyperparathyroidism and lower in patients with chronic renal failure than in normal subjects. In patients with medullary carcinoma of the thyroid, the serum calcitonin levels were elevated, but the parathyroid hormone and 1,25-(OH)2D levels were within normal ranges. The serum 25OHD levels were not significantly different in any group. It is concluded that chronic elevation of serum calcitonin has no effect on the serum 1,25-(OH)2D level.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Calcitonin; Calcitriol; Carcinoma; Ergocalciferols; Female; Humans; Hypoparathyroidism; Kidney Failure, Chronic; Male; Middle Aged; Thyroid Neoplasms

The basal values of plasma vitamin D metabolites were evaluated in patients with primary hyperparathyroidism (1 degree HPT, n = 31), hypoparathyroidism (HP, n = 7), pseudohypoparathyroidism (PHP, n = 4) and normal controls (n = 21). Plasma 25-hydroxyvitamin D (25-OH-D) in 1 degree HPT (9.0 +/0 7.3 ng/ml, mean SD) was significantly lower than that of normal controls (17.9 +/- 5.5ng/ml)(p less than 0.001), and in particular 1 degree HPT classified as the skeletal type showed extremely low value (4.7 +/- 4.6 ng/ml). Plasma 1, 25-dihydroxyvitamin D [1, 25-(OH)2D] was significantly higher in 1 degree HPT (69.1 +/- 31.4pg/ml)(p less than 0.001) and significantly lower in Hp (15.2 +/- 11.0 pg/ml) (p less than 0.001) compared to normal controls (37.2 +/- 13.8pg/ml), although there was no significant difference in PHP (22.3 +/- 17.5 pg/ml). Plasma 24, 25-dihydroxyvitamin D [24,, 25-(OH)2D] in 1 degree HPT (1.06 +/- 0.55 ng/ml) was significantly lower than that of normal controls (1.73 +/- 0.62 ng/ml) (p less than 0.05), and particularly 1 degree HPT classified as the skeletal type showed a marked low value (0.85 +/- 0.27 ng/ml), whereas no significant differences were seen in HP (1.84 +/- 0.46 ng/ml) or PHP (1.34 +/- 0.22 ng/ml). There were slight but significant correlations between either plasma 25-OH-D and 1, 25-(OH)2D (r = -0.350, p less than 0.05), or plasma 25-OH-D and 24, 25-(OH)2D (r = 0.356, p less than 0.05), or plasma 1, 25-(OH)2D and 24, 25-(OH)2D (r = -0.444, p less than 0.01) in all subjects. In addition, relationships between plasma vitamin D metabolites and other indicators of parathyroid function in all subjects were analyzed. There were positive correlations between plasma 1, 25-(OH)2D and serum Ca (r = -0.621, p less than 0.001) or urinary cAMP (r = -0.671, p less than 0.001) or nephrogenous cAMP (r = -0.689, p less than 0.001), while negative correlations were seen between plasma 1, 25-(OH)2D and serum P (r = -0.680, p less than 0.001) or %TRP (r = -0.663, p less than 0.001). On the other hand, there were negative correlations between plasma 24, 25-(OH)2D and serum Ca (r = -0.457, p less than 0.01) or urinary cAMP (r = -0.562, p less than 0.005) or nephrogenous cAMp (r = -0.561, p less than 0.005), and a positive correlation was seen between plasma 24, 25-(OH)2D and %TRP (r = 0.519, p less than 0.005). After parathyroidectomy, a distinct depression of plasma 1, 25-(OH)2D and reciprocal elevation of plasma 24, 25-(OH)2D were observed in 1 degree

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Aged; Calcium; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Male; Middle Aged; Phosphorus; Pseudohypoparathyroidism

Oral administration of prednisone (30 mg/day for 9 days) to six normal individuals induced a significant rise in the concentration of serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] within 2 days. In four patients with primary hyperparathyroidism a larger increase of 1,25-(OH)-2D was observed within 3 days. In these patients the 1,25-(OH)-2D concentration remained elevated during the whole period of prednisone administration (10 days) whereas in the control group it had returned to basal levels or below after 9 days of prednisone administration. This response appeared dependent upon parathyroid hormone (PTH) as we found no change in the (basally low) 1,25-(OH)2D concentrations in five patients with hypoparathyroidism during 3-4 days of prednisone administration (30 mg/day). In these patients vitamin D medication had been interrupted 3-5 days before the administration of prednisone, whereafter serum calcium was kept between 2.10 and 2.30 mmol/1 by means of calcium infusion. The response of 1,25-(OH)2D to prednisone is best explained by a stimulatory action of glucocorticoids upon PTH secretion or by the induction of increased PTH sensitivity.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Adult; Aged; Calcitriol; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hyperparathyroidism; Hypoparathyroidism; Male; Middle Aged; Prednisone

Only moderately reduced serum 1,25-dihydroxyvitamin D [1,25(OH)2D3] levels were found in 13 hypoparathyroid patients and in 1 pseudohypoparathyroid patient, indicating that factors other than parathyroid hormone are able to mediate the basal production of 1,25(OH)2D3. A significant correlation was found between the levels of circulating 25-hydroxyvitamin D (25OHD) and 1,25(OH)2D, suggesting that a high concentration of 25OHD was able to increase the renal production of 1,25(OH)2D, whereas hypocalcemia and changes in serum phosphate became less important in the present situation. The serum 25OHD and 1,25(OH)2D concentrations were followed during the change of treatment from ergocalciferol to 1 alpha-hydroxycholecalciferol (1 alpha-OHD3). A biological half-life of 3 weeks could be estimated for the plasma 25OHD. The increase in serum 1,25(OH)2D correlated with the dose of 1 alpha-OHD3 given, whereas no correlation was found between the serum calcium level and the 1,25(OH)2D concentration. Unexpected increases and decreases in serum calcium were observed at the same dose of 1 alpha-OHD3 in the same patient and at serum 1,25(OH)2D concentrations within the physiological range.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Calcitriol; Calcium; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hydroxycholecalciferols; Hypoparathyroidism; Kinetics; Male