25-hydroxyvitamin-d-2 and Hypercalcemia

Vitamin D deficiency is common worldwide, contributing to nutritional rickets and osteomalacia which have a major impact on health, growth, and development of infants, children and adolescents. Vitamin D levels are low in breast milk and exclusively breastfed infants are at risk of vitamin D insufficiency or deficiency.. To determine the effect of vitamin D supplementation given to infants, or lactating mothers, on vitamin D deficiency, bone density and growth in healthy term breastfed infants.. We used the standard search strategy of Cochrane Neonatal to 29 May 2020 supplemented by searches of clinical trials databases, conference proceedings, and citations.. Randomised controlled trials (RCTs) and quasi-RCTs in breastfeeding mother-infant pairs comparing vitamin D supplementation given to infants or lactating mothers compared to placebo or no intervention, or sunlight, or that compare vitamin D supplementation of infants to supplementation of mothers.. Two review authors assessed trial eligibility and risk of bias and independently extracted data. We used the GRADE approach to assess the certainty of evidence.. We included 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to lactating mothers (eight studies), and to infants versus lactating mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure. Vitamin D supplementation given to infants: vitamin D at 400 IU/day may increase 25-OH vitamin D levels (MD 22.63 nmol/L, 95% CI 17.05 to 28.21; participants = 334; studies = 6; low-certainty) and may reduce the incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L) (RR 0.57, 95% CI 0.41 to 0.80; participants = 274; studies = 4; low-certainty). However, there was insufficient evidence to determine if vitamin D given to the infant reduces the risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age (RR 0.41, 95% CI 0.16 to 1.05; participants = 122; studies = 2), affects bone mineral content (BMC), or the incidence of biochemical or radiological rickets (all very-low certainty). We are uncertain about adverse effects including hypercalcaemia. There were no studies of higher doses of infant vitamin D (> 400 IU/day) compared to placebo. Vitamin D supplementation given to lactating mothers: vitamin D supplementation given to lactating mothers may increase infant 25-OH vitamin D levels (MD 24.60 nmol/L, 95% CI 21.59 to 27.60; participants = 597; studies = 7; low-certainty), may reduce the incidences of vitamin D insufficiency (RR 0.47, 95% CI 0.39 to 0.57; participants = 512; studies = 5; low-certainty), vitamin D deficiency (RR 0.15, 95% CI 0.09 to 0.24; participants = 512; studies = 5; low-certainty) and biochemical rickets (RR 0.06, 95% CI 0.01 to 0.44; participants = 229; studies = 2; low-certainty). The two studies that reported biochemical rickets used maternal dosages of oral D3 60,000 IU/day for 10 days and oral D3 60,000 IU postpartum and at 6, 10, and 14 weeks. However, infant BMC was not reported and there was insufficient evidence to determine if maternal supplementation has an effect on radiological rickets (RR 0.76, 95% CI 0.18 to 3.31; participants = 536; studies = 3; very low-certainty). All studies of maternal supplementation enrolled populations at high risk of vitamin D deficiency. We are uncertain of the effects of maternal supplementation on infant growth and adverse effects including hypercalcaemia. Vitamin D supplementation given to infants compared with supplementation given to lactating mothers: infant vitamin D suppl. For breastfed infants, vitamin D supplementation 400 IU/day for up to six months increases 25-OH vitamin D levels and reduces vitamin D insufficiency, but there was insufficient evidence to assess its effect on vitamin D deficiency and bone health. For higher-risk infants who are breastfeeding, maternal vitamin D supplementation reduces vitamin D insufficiency and vitamin D deficiency, but there was insufficient evidence to determine an effect on bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants led to greater increases in infant 25-OH vitamin D levels, reductions in vitamin D insufficiency and vitamin D deficiency compared to supplementation of lactating mothers. However, the evidence is very uncertain for markers of bone health. Maternal higher dose supplementation (≥ 4000 IU/day) produced similar infant 25-OH vitamin D levels as infant supplementation of 400 IU/day. The certainty of evidence was graded as low to very low for all outcomes.

Topics: 25-Hydroxyvitamin D 2; Bone and Bones; Bone Density; Breast Feeding; Female; Humans; Hypercalcemia; Infant; Lactation; Mothers; Randomized Controlled Trials as Topic; Rickets; Term Birth; Vitamin D; Vitamin D Deficiency; Vitamins

To evaluate whether tuberculosis-associated hypercalcemia is related to abnormal synthesis of 1,25-dihydroxyvitamin D (1,25[OH]2D) and whether ketoconazole administration may be useful in treating tuberculosis-associated hypercalcemia.. Case study.. Endocrine Unit, Pediatric Clinic, University of Pisa (Italy).. Two boys (aged 10.5 years and 14.7 years) with active tuberculosis and hypercalcemia.. At admission, serum 1,25-dihydroxyvitamin D levels were elevated. Oral ketoconazole administration (3.0 mg/kg every 8 hours) decreased 1,25-dihydroxyvitamin D levels within the first week of therapy (from 208.8 to 57.6 pmol/L [-72.4%] in one boy and from 321.6 to 115.2 pmol/L [-64.2%] in the other). We also found a coincident normalization of serum ionized calcium concentration (from 1.45 to 1.24 mmol/L [-13.0%] in one boy and from 1.55 to 1.26 mmol/L [-17.0%] in the other).. Abnormal elevated levels of 1,25-dihydroxyvitamin D caused hypercalcemia in our patients; ketoconazole administration may be effective in the treatment of hypercalcemia in patients with tuberculosis, which decreases 1,25-dihydroxyvitamin D synthesis.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Calcitriol; Calcium; Child; Creatinine; Humans; Hydrocortisone; Hypercalcemia; Ketoconazole; Male; Parathyroid Hormone; Phosphorus; Radiography; Thyroid Function Tests; Tuberculosis, Pulmonary

Vitamin D deficiency is a common problem worldwide. Several studies have shown an association between vitamin D deficiency and the increased risk of metabolic syndrome. No previous study has compared the efficacy and safety of ergocalciferol at 40,000 versus 20,000 IU/week in patients with metabolic syndrome.. To evaluate the efficacy of ergocalciferol supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentrations and to examine safety parameters in metabolic syndrome patients.. Outpatient department of Phramongkutklao Hospital, Bangkok, Thailand.. A randomized, double-blinded, parallel study was conducted in metabolic syndrome patients with vitamin D deficiency [25(OH)D <20 ng/mL]. Ninety patients were randomly assigned into three groups of 30 patients each. Group 1 was given two capsules of placebo/week, group 2 was given ergocalciferol 20,000 IU/week, and group 3 was given ergocalciferol 40,000 IU/week for 8 weeks.. serum 25(OH)D concentrations, serum calcium, safety, and corrected QT (QTc) interval.. Of the 90 patients enrolled, 84 patients completed the study. At the end of the study, the mean serum 25(OH)D in groups 2 and 3 significantly increased from the baseline (15.1 and 14.3 to 26.8 and 30.0 ng/mL, respectively). The increase in serum 25(OH)D in groups 2 and 3 were comparable and significantly greater than that of the placebo group. The percentage number of patients achieving normal vitamin D levels in groups 1, 2 and 3 were 3.3, 33.3, and 60.0 %, respectively, which were significantly different between groups (p < 0.001). Adverse reactions in both ergocalciferol treatment groups were not different from the placebo group (p > 0.05). Serum calcium levels did not change within and between groups of treatment. No significant change in QTc was observed in any patient.. Both 20,000 and 40,000 IU/week of ergocalciferol supplementation for 8 weeks were able to increase serum 25(OH)D concentrations significantly. However, more patients in the ergocalciferol 40,000 IU/week treatment group achieved a normal serum 25(OH)D level than in the group which received 20,000 IU/week. Clinicians would have informed of choosing the dosing regimen of ergocalciferol in metabolic syndrome patients.

Topics: 25-Hydroxyvitamin D 2; Aged; Arrhythmias, Cardiac; Calcifediol; Calcium; Dietary Supplements; Double-Blind Method; Ergocalciferols; Female; Humans; Hypercalcemia; Incidence; Male; Metabolic Syndrome; Middle Aged; Thailand; Time Factors; Vitamin D Deficiency

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

Lithium can influence calcium homeostasis resulting in changes in parathormone set point and renal calcium handling. The clinical significance of these changes in older patients is unknown. The objective of this study was to investigate the possible association between duration of lithium treatment and corrected calcium, parathormone and 24-h urinary calcium excretion in older psychiatric patients corrected for renal function and vitamin 25OH D and also to estimate the point prevalence of hypercalcemia and raised parathormone.. A cross-sectional study of psychiatric outpatients visiting a specialized facility for older patients treated with lithium was performed. Patients underwent a comprehensive assessment and blood and urine testing. Potential confounders of calcium homeostasis were recorded. On the basis of the duration of lithium treatment, patients were divided into four groups.. One hundred eleven patients were included, mean age 75.2 years. There was no significant association between the duration of lithium treatment and corrected calcium, parathormone and 24-h urinary calcium excretion. The point prevalence of hypercalcemia was 2.7% and 47.8% for raised parathormone. There was an unexpected but significant negative association between the duration of lithium treatment and vitamin 25OH D, with 76.9% vitamin 25OH D deficiency (<50 nmol/L) in the group using lithium for more than 10 years.. No association was found between duration of lithium treatment and calcium parameters in older psychiatric outpatients, but there was a high prevalence of raised parathormone and an unexpected negative association between duration of lithium treatment and 25OH D.

Topics: 25-Hydroxyvitamin D 2; Aged; Aged, 80 and over; Antipsychotic Agents; Calcium; Cross-Sectional Studies; Female; Homeostasis; Humans; Hypercalcemia; Lithium; Male; Mental Disorders; Netherlands; Parathyroid Hormone

Vitamin D deficiency is common in patients with chronic kidney disease (CKD). Current guidelines recommend treatment strategies in these patients similar to those for the general population, but the vitamin D nutritional status sufficient to prevent PTH levels from increasing in CKD is unknown. OBJECTIVE, MAIN OUTCOME MEASURE: Our aim was to study the relation between circulating PTH and 25(OH)D levels and to search for a 25(OH)D threshold associated with a significant PTH increase.. In the hospital-referred NephroTest cohort study, we measured 25(OH)D, PTH, and glomerular filtration rate (mGFR) by ⁵¹Cr-EDTA renal clearance in 929 adult patients with nondialysis CKD stages 1 to 5 and no vitamin D supplementation. Patients' mean age was 60.1 ± 14.7 years; 71% were men, and 9% were black. Their median mGFR was 37.8 mL/min/1.73 m².. We found a 25(OH)D threshold of 8 ng/mL with an upper limit of 20 ng/mL (95% confidence interval) by linear piecewise regression modeling of log-PTH for 25(OH)D adjusted for mGFR, age, race, and ionized calcium level. The smoothed curve confirmed that PTH concentration rose steeply when circulating 25(OH)D levels fell to less than 20 ng/mL.. Spontaneous 25(OH)D levels greater than 20 ng/mL seem sufficient to control serum PTH in CKD patients. This result reinforces guidelines to supplement vitamin D only if less than 30 ng/mL.

Topics: 25-Hydroxyvitamin D 2; Aged; Calcifediol; Calcium; Cohort Studies; Female; France; Glomerular Filtration Rate; Humans; Hypercalcemia; Male; Middle Aged; Parathyroid Hormone; Phosphates; Practice Guidelines as Topic; Prevalence; Prospective Studies; Renal Insufficiency, Chronic; Severity of Illness Index; Vitamin D Deficiency

Intoxication from vitamin D supplements has been rarely reported but, nowadays, it occurs more frequently. 3-epi-25-OH-D(3) is highly prevalent in adults and it is considered of biological relevance. We report a case of vitamin D toxicity with hypercalcemia, acute renal failure and hypervitaminosis A after consuming an over-the-counter vitamin D supplement. Our data suggest that the contribution of 3-epi-25-OH-D(3) is not altered during vitamin D toxicity, although the serum levels of 25-OH-D(3) and 3-epi-25-OH-D(3) may display a different rate of clearance. The patient also displayed hypervitaminosis A unrelated to diet, possibly caused by renal failure related to the hypercalcemia induced by vitamin D toxicity. Because of the increasing use of over-the-counter vitamin D supplements and the potential iatrogenic hypercalcemia related to hypervitaminosis A, the present case highlights the importance of evaluating both the use of (non-) prescribed medication and vitamin A status during vitamin D toxicity.

Topics: 25-Hydroxyvitamin D 2; Acute Kidney Injury; Calcifediol; Chromatography, High Pressure Liquid; Dietary Supplements; Female; Humans; Hypercalcemia; Hypervitaminosis A; Medical Errors; Middle Aged; Quality Control; Vitamin A; Vitamin D; Vitamins

Topics: 25-Hydroxyvitamin D 2; Antineoplastic Agents; Biopsy; Bronchoscopy; Calcitriol; Calcium; Female; Follow-Up Studies; Humans; Hypercalcemia; Lung Neoplasms; Lymphomatoid Granulomatosis; Middle Aged; Peripheral Nervous System Diseases; Radiography, Thoracic; Thoracoscopy

A patient with non-Hodgkin's lymphoma associated hypercalcaemia and a raised serum concentration of 1,25(OH)2D is described. Interestingly, both abnormalities were corrected with treatment. Data implicating calcitriol as an important immunoregulatory hormone are discussed.

Topics: 25-Hydroxyvitamin D 2; Aged; Calcitriol; Female; Humans; Hypercalcemia; Lymphoma, B-Cell

Vitamin D metabolites were measured on admission in eight patients intoxicated with ergocalciferol (serum calcium 3.01-4.05 mmol/l) and also during the subsequent 2 months in six of the eight. Serum concentrations of 25-hydroxyergocalciferol, on admission, were grossly elevated in all patients (range 583-1843 nmol/l). Serum calcium concentration was related significantly only to the concentration of 25-hydroxyergocalciferol (P = 0.003). Concentrations of 25-hydroxyergocalciferol in serum were significantly related to those of calciferol (P = 0.004). Elevated initial concentrations of 1,25-dihydroxycalciferol, mainly as 1,25-dihydroxyergocalciferol, were found in seven of the eight patients (range 179-313 pmol/l). It is suggested that the hypercalcaemia in these patients may be explained by the action of 25-hydroxyergocalciferol at high concentration in competing for 1,25-dihydroxycalciferol receptors, thus exerting a biological effect per se, and also by increasing the synthesis of 1,25-dihydroxycalciferol through a mass-action effect on the renal 1 alpha-hydroxylase.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Aged; Calcium; Ergocalciferols; Female; Humans; Hypercalcemia; Male; Middle Aged; Vitamin D

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

Two patients with disseminated coccidioidomycosis and hypercalcemia are presented. One patient studied showed normal levels of 25-hydroxyvitamin D with depressed levels of 1 alpha,25-dihydroxyvitamin D. The serum calcitonin level was appropriate for the level of serum calcium, and the serum parathyroid hormone level was suppressed with elevation of the nephrogenous cAMP level. Intestinal absorption of calcium was elevated at 63 percent. Hypercalcemia and hypercalciuria persisted despite a 300 mg calcium diet. An osteotropic substance similar to the humoral hypercalcemia of malignancy is postulated.

Topics: 25-Hydroxyvitamin D 2; Adult; Calcitonin; Calcium; Coccidioidomycosis; Ergocalciferols; Female; Humans; Hypercalcemia; Intestinal Absorption; Male

Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.

Topics: 25-Hydroxyvitamin D 2; Animals; Calcifediol; Calcium; Cattle; Cattle Diseases; Cholecalciferol; Ergocalciferols; Female; Hydroxycholecalciferols; Hydroxyproline; Hypercalcemia; Injections, Intramuscular; Labor, Obstetric; Magnesium; Phosphorus; Pregnancy

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

Delayed hypercalcemia developed in two patients with acute renal failure and rhabdomyolysis. In patient 1, the hypercalcemia appeared 14 days after the beginning of the diuretic phase of the illness and was associated with severe diastolic hypertension and soft-tissue calcification, including the lungs and skeletal muscles. The blood levels of 25-hydroxyvitamin D (25OHD3) were elevated during the hypercalcemia and decreased to normal when the patient became normocalcemic. In patient 2, the hypercalcemia occurred 55 days after the start of the diuretic phase and at a time when renal function was normal.

Topics: 25-Hydroxyvitamin D 2; Acute Kidney Injury; Adolescent; Adult; Calcium; Diuresis; Humans; Hydroxycholecalciferols; Hypercalcemia; Male; Muscles; Myoglobinuria; Time Factors

The authors report on a new case of severe hypercalcaemia induced by prolonged oral treatment with high doses of vitamin D2. (6 mg/day for 9 months). Blood calcium level did not return to normal until 6 months after the drug was discontinued. The plasma concentration of 25 (OH) D was more than three times the normal value and remained very high throughout the observation period. The plasma concentration of 24, 25 (OH)2 D was slightly raised during treatment but became normal after 15 days, while that of 1,25 (OH)2 D, the active form of vitamin D, remained normal throughout, suggesting that the pathogenesis of vitamin D-induced hypercalcaemia is probably complex.

Topics: 25-Hydroxyvitamin D 2; Aged; Ergocalciferols; Female; Humans; Hypercalcemia; Vitamin D