Vitamin D3 AND hypercalcemia

Immunoglobulin G4-related disease (IgG4-RD)-associated hypercalcemia has rarely been reported. We report a case of IgG4-RD that presented as severe symptomatic hypercalcemia. A 50-year-old woman with a history of sustained bilateral periorbital swelling and proptosis for more than 5 years presented to our hospital complaining of a 3-day history of significant and progressive nausea, vomiting, loss of appetite, fatigue, and pruritus. She denied a long history of medication. On admission, laboratory tests showed severe hypercalcemia with serum adjusted calcium elevated to 4...

OBJECTIVES: Compare the efficacy and safety of daily vs. monthly oral vitamin D3 in treating symptomatic vitamin D deficiency in infants. METHODS: 90 infants with symptomatic vitamin D deficiency were randomized into Daily (D) [46 infants] and Bolus (B) [44 infants] groups to receive oral vitamin D3 , daily (2000 IU/day) and bolus (60,000 IU/month) for three months respectively. Both groups received daily oral calcium @50 mg/kg/day. Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol [25(OH)D], parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 and 12 weeks...

Many controversies exist regarding vitamin D3 supplementation. These include not only diseases that are responsive to vitamin D supplementation, but also the long-term safety of prolonged daily oral vitamin D3 intake above 4000-10,000 International Units (IU). In particular, supplementation levels that do not result in adverse events, and the upper limits of safe serum 25-hydroxyvitamin D (25OHD) concentrations. Adverse reactions reported to occur with excessive vitamin D intake include hypercalcemia, renal failure, calcium crystal formation, undetectable parathyroid hormone concentrations, and hypercalciuria, all of which are reported to be reversible...

BACKGROUND: Different studies have shown that hemodialysis patients require higher doses of Vitamin D3 (VD3) than the general population to achieve satisfactory replenishment. This study aims to assess the safety of such practice and its benefits on some of the parameters of Chronic Kidney Disease- Mineral and Bone Disorder (CKD-MBD). METHODS: A single-center clinical trial assessing the benefits of high dose VD3 in hemodialysis patients. The dose of VD3 (300,000 IU) was administered orally and monthly from April to December 2020 (9 months) at the dialysis unit...

Sarcoidosis is primarily a disease of the lungs, and extrapulmonary manifestations are rare. Herein we report a case of isolated bone marrow sarcoidosis presenting as symptomatic hypercalcemia. A 75-year-old female presented with complaints of confusion, dizziness, headaches, and tremulousness. Workup was unremarkable save for hypercalcemia and elevated serum 1,25(OH)D3. Bone marrow biopsy revealed non-caseating granulomas suggestive of sarcoidosis. She was treated with a slow prednisone taper and her symptoms resolved...

PURPOSE: The upper tolerable intake level for vitamin D in the general population has been set at 4000 international units (IU) daily, but considerable uncertainty remains. We summarized reported harmful effects of a daily vitamin D supplement of 3200-4000 IU in trials lasting ≥ 6 months. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials in several databases and identified 22 trials reporting safety data...

We report on a 53-year-old female patient and a 33-year-old male patient presenting with life-threatening hypercalcemic crisis caused by self-induced vitamin-D intoxication. Both patients took high doses of vitamin D3 supplements, cumulatively up to 2,500,000-10,000,000 I.U. over several months. Accordingly, serum 25-OH-vitamin D concentrations were increased to 663 and 1289 nmol/L (reference 50-175 nmol/L), respectively. As forced diuresis and bisphosphonates failed to correct recurrent hypercalcemia, we hypothesized that add-on extracorporeal treatments might help overcome the refractory situation...

Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2 D3 ...

A personalized vitamin D3 loading dose has not yet been tested in cancer patients. This interim analysis of the randomized, placebo-controlled VICTORIA trial analyzed the first recruited 74 German adults with nonmetastatic colorectal cancer, a tumor surgery within the past year, and 25-hydroxyvitamin D levels (25(OH)D) < 50 nmol/L. Study participants received a loading dose tailored for a baseline 25(OH)D level and BMI in the first 11 days, followed by a maintenance dose of 2000 IU of vitamin D3 daily until end of trial week 12...

BACKGROUND: Vitamin D is a dietary micronutrient responsible for calcium and phosphorus metabolism and multiple extraskeletal actions. The assessment of vitamin D status is commonly based on measurement of 25(OH)D total concentration in serum. However, the usage of liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique allows to reliably assess a panel of vitamin D metabolites in serum or plasma, which may help to investigate the metabolic paths of vitamin D, especially in populations at risk of deficiency...

RATIONALE: There are many causes of hypercalcemia, with hyperparathyroidism and malignancy accounting for 90% of cases. Sarcoidosis and the intake of vitamin D supplements may also cause hypercalcemia, although the occurrence rate is low if only one is involved. We herein report a sarcoidosis patient who developed hypercalcemia after taking cholecalciferol (vitamin D supplement) for a year. PATIENT CONCERN: A 62-year-old Japanese man presented with hypercalcemia and acute kidney injury along with symptoms of fatigue and appetite loss while being followed up for sarcoidosis...

OBJECTIVE: Observational studies suggest that higher serum 25-hydroxyvitamin D concentration may be associated with lower risk of cataract. However, no randomized controlled trials (RCTs) have assessed the effect of vitamin D supplementation on the incidence of cataract. We aimed to assess whether vitamin D supplementation reduces the incidence of cataract surgery. DESIGN: We conducted an ancillary study of D-Health Trial, a randomized, double-masked, placebo-controlled trial of monthly vitamin D for the prevention of all-cause mortality conducted from 2014 to 2020 within the Australian general population...

BACKGROUND: A systematic review was commissioned to support an international expert group charged to update the Food and Agriculture Organisation of the United Nations (FAO)/World Health Organisation (WHO)'s vitamin D intake recommendations for children aged 0-4 years. MATERIALS AND METHODS: Multiple electronic databases were searched to capture studies published from database inception to the 2nd week of June 2020 according to key questions formulated by the FAO/WHO...

Infantile hypercalcemia type 1 (HCINF1), previously known as idiopathic infantile hypercalcemia, is caused by mutations in the 25-hydroxyvitamin D 24-hydroxylase gene, CYP24A1 . The R396W loss-of-function mutation in CYP24A1 is the second most frequent mutated allele observed in affected HCINF1 patients. We have introduced the site-specific R396W mutation within the murine Cyp24a1 gene in knock-in mice to generate a humanized model of HCINF1. On the C57Bl6 inbred background, homozygous mutant mice exhibited high perinatal lethality with 17% survival past weaning...

Hypercalcemia is a rare condition in pregnancy. It is most commonly caused by primary hyperparathyroidism and parathyroid hormone-related peptid (PTHrP)-producing malignant tumours, less frequently by increased intestinal calcium absorption, vitamin D intoxication, milk-alkali syndrome, and granulomatous diseases or lymphomas, in which vitamin D 1α-hydroxylase expression is increased. Rarely, gestational hypercalcaemia may be caused by a disorder of vitamin D catabolism caused by loss-of-function mutations in the CYP24A1 gene...

BACKGROUND: Pharmacological therapy may be useful in the treatment of moderate to severe hypercalcemia in patients with infantile hypercalcemia-1 (HCINF1) due to pathogenic variants in the cytochrome P450 24 subfamily A member 1 (CYP24A1). Rifampin is an antituberculosis drug that is a potent inducer of cytochrome P450 3 subfamily A member 4, which is involved in an alternative catabolic pathway of vitamin D. The efficacy of rifampin in improving hypercalcemia was previously reported, but many questions remain on the long-term efficacy and safety...

Blood levels of the vitamin D3 (D3 ) metabolites 25-hydroxyvitamin D3 (25(OH)D3 ), 24 R ,25-dihydroxyvitamin D3 , and 1α,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) are recognized indicators for the diagnosis of bone metabolism-related diseases, D3 deficiency-related diseases, and hypercalcemia, and are generally measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS) using an isotope dilution method. However, other D3 metabolites, such as 20-hydroxyvitamin D3 and lactone D3 , also show interesting biological activities and stable isotope-labeled derivatives are required for LC-MS/MS analysis of their concentrations in serum...

BACKGROUND: In 2013, the group of Cicero Coimbra, Brazil, reported the clinical efficacy of high doses of vitamin D3 in patients suffering from autoimmune skin disorders ("Coimbra protocol", CP). However, hypercalcemia and the subsequent impaired renal function may be major concerns raised against this protocol. METHODS: We report for the first time for a broad spectrum of autoimmune diseases in 319 patients (mean age (±SD) 43.3 ± 14.6 years, 65.5% female, 34...

BACKGROUND: Observational studies suggest that vitamin D deficiency among people living with HIV is associated with a greater risk of disease progression and death. Low levels of vitamin D in pregnancy are also associated with poor fetal and infant growth. Therefore, vitamin D supplementation may improve clinical outcomes for pregnant women living with HIV and improve fetal and postnatal growth for their infants. METHODS AND FINDINGS: We conducted a randomized, triple-blind, placebo-controlled trial of vitamin D3 supplementation among pregnant and lactating women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials...

Kidneys are key regulators of phosphate homeostasis. Biallelic mutations of the renal Na+ /phosphate cotransporter SLC34A1/NaPi-IIa cause idiopathic infantile hypercalcemia, whereas monoallelic mutations were frequently noted in adults with kidney stones. Genome-wide-association studies identified SLC34A1 as a risk locus for chronic kidney disease. Pathogenic mutations in SLC34A1 are present in 4% of the general population. Here, we characterize a mouse model carrying the 91del7 in-frame deletion, a frequent mutation whose significance remains unclear...