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Humoral Hypercalcaemia in Metastatic Gallbladder Cancer Presenting as Delirium: A Case Report.

Hypercalcaemia of malignancy (HCM) is a recognised paraneoplastic complication of advanced cancer, with HHM being mediated predominantly by parathyroid hormone-related protein (PTHrP) secretion. While commonly observed in squamous cell carcinomas, it is exceedingly rare in gallbladder adenocarcinoma, with only isolated case reports described in the literature. We report a man in his 50s with metastatic gallbladder cancer who presented with colicky abdominal pain, constipation, fatigue, low mood, delayed responses and insomnia. Delirium was diagnosed based on the Diagnostic and Statistical Manu

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… Among haematologic malignancies, multiple myeloma shows the highest prevalence (7–10%). [ 4 , 5 ] Four principal mechanisms underlie malignancy-related hypercalcaemia: secretion of PTHrP in about 80% of cases, osteolytic metastases in around 20%, ectopic calcitriol production and rarely ectopic PTH … Measurement of PTHrP and calcitriol subsequently helps differentiate humoral hypercalcaemia of malignancy from calcitriol-mediated hypercalcaemia, such as that seen in lymphoma. …

Cancer-related hypercalcemia and potential treatments.

Cancer-related hypercalcemia is a common finding typically seen in patients with advanced cancer and occurs in about 20 to 30 percent of cases. The most common cause of hypercalcemia in hospitalized patients is hypercalcemia due to malignancy.This clinical problem is seen in patients with both solid tumors and patients with hematologic malignancies. Hypercalcemia is associated with a poor prognosis in oncology patients. This pathologic condition can occur due to many different mechanisms but is usually caused by abnormal calcium use resulting from bone resorption, intestinal absorption, or ren

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… Uncontrolled production of 1,25-dihydroxyvitamin D (calcitriol) is the cause of almost all cases of hypercalcemia in Hodgkin lymphoma and about one-third of cases of non-Hodgkin lymphoma ( 20 , 21 ). … Glucocorticoids can suppress the synthesis of extrarenal calcitriol through activated mononuclear cells in the lung and lymph nodes. Namely, by inhibiting 1-alpha hydroxylase, they inhibit 1,25(OH)2 D synthesis and thus calcium absorption from the intestine ( 86 ). …

BCG stimulation promotes dendritic cell proliferation and expression of VDR and CYP27B1 in vitamin D‑deficient mice.

Vitamin D deficiency may lead to an increased risk of tuberculosis. In the present study, the effects of Mycobacterium tuberculosis (Mtb) infection on dendritic cells (DCs) derived from vitamin D‑deficient mice or normal control mice were investigated. A vitamin D‑deficient mouse model was established, and bone marrow‑derived DCs (BMDCs) were isolated and treated with GM‑CSF and interleukin (IL)‑4 for 6 days, followed by an additional 24 h of treatment with Bacillus Calmette‑Guérin (BCG). The expression levels of surface molecules of DCs, including integrin alpha‑X and T‑lymphocyte activation

δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system.

There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the δ-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p=0.01). The Pb levels in blood (B-Pb) and urine (U-

Physical and functional interaction between the vitamin D receptor and hairless corepressor, two proteins required for hair cycling.

Both the vitamin D receptor (VDR) and hairless (hr) genes play a role in the mammalian hair cycle, as inactivating mutations in either result in total alopecia. VDR is a nuclear receptor that functions as a ligand-activated transcription factor, whereas the hairless gene product (Hr) acts as a corepressor of both the thyroid hormone receptor (TR) and the orphan nuclear receptor, RORalpha. In the present study, we show that VDR-mediated transactivation is strikingly inhibited by coexpression of rat Hr. The repressive effect of Hr is observed on both synthetic and naturally occurring VDR-respons

Prophylactic thyroidectomy, based on direct genetic testing, in patients at risk for the multiple endocrine neoplasia type 2 syndromes.

Since the discovery that germ-line mutations in the RET protooncogene are responsible for the multiple endocrine neoplasia (MEN) syndromes types 2A and 2B, prophylactic thyroidectomy has been recommended for MEN patients to prevent medullary thyroid carcinoma (MTC). In this report, we present the medium-term follow up results on the earliest group of 18 patients having prophylactic thyroidectomy for MEN 2A. There were no operative complications. Microscopic or grossly evident MTC was present in 14 (78%) of the resected patients. None of the patients had metastasis of their MTC to regional lymp

Stable transfection of U937 cells with sense or antisense RXR-alpha cDNA suggests a role for RXR-alpha in the control of monoblastic differentiation induced by retinoic acid and vitamin D.

Although retinoic acid (RA) has been known for many years to be a modulating agent that plays a role in generating both granulocytes and monocytes, the molecular mechanism underlying this role has not been defined in the monoblast lineage. In particular, the part played by the retinoid X receptors (RXRs), which are members of the steroid/thyroid hormone nuclear receptor family, has not been explored. In this study, therefore, the human monoblastic leukemia cell line U937 has been used as a model system to investigate the role of one of the RXRs, RXR-alpha, in monoblast differentiation. RXR-alp

Syndrome of lipoatrophic diabetes, vitamin D resistant rickets, and persistent Müllerian ducts in a Turkish boy born to consanguineous parents.

Congenital lipodystrophy (MIM 269700), persistent Müllerian ducts (MIM 261550), and vitamin D resistant rickets (MIM 277440) were observed in an 8 1/2-year-old boy born to consanguineous parents. Measurements of hormone sensitive lipase activity from a sample of the suprapubic fat depot were normal. Although the insulin receptor appeared normal (including autophosphorylation), insulin action, assessed by induction of total mRNA, was decreased. The vitamin D receptor was normal in size and amount, with a slight decrease in affinity for 1,25(OH)2D3. Induction of 24-hydroxylase, used as a measure

Pathophysiology and treatment of osteoporosis: challenges for clinical practice in older people.

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people.

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… Inactive vitamin D is hydroxylated first by 25-hydroxylase (CYP2R1) in the liver and is then converted to its active form, calcitriol (1,25[OH] 2 D 3 ), in the kidneys by 1a-hydroxylase (CYP27B1). PTH stimulates 1α-hydroxylase to increase levels of calcitriol. … When serum calcium levels are normal or low, calcitriol acts on vitamin D receptors (VDRs) to increase intestinal and renal calcium uptake. …

Severe Hypocalcemia and Hypomagnesemia with Denosumab in Advanced Chronic Kidney Disease: Case Report and Literature Review.

BackgroundDenosumab has become the preferred agent over zolendronic acid to help prevent skeletal-related events in patients with metastatic bone disease and multiple myeloma because it is approved for use in those with kidney dysfunction. However, denosumab has been linked to cases of hypocalcemia, particularly in those with advanced kidney disease.Case presentationWe present the case of a patient with metastatic prostate cancer and chronic kidney disease due to obstructive nephropathy who developed severe hypocalcemia and hypomagnesemia after denosumab injection, which required intensive car

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… He was discharged on 0.5 μ g oral calcitriol daily, calcium carbonate 1000 mg BID, and continued intermittent hemodialysis. The patient was originally diagnosed with de novo metastatic prostate cancer two years prior. … Hypomagnesemia is also associated with low calcitriol levels which can also increase the risk of hypocalcemia with denosumab use in CKD [ 20 ]. …

Clinical approaches to osteoporosis in patients with chronic kidney disease: A comprehensive review.

Chronic kidney disease (CKD) induces secondary osteoporosis, characterized by an imbalance between bone formation and resorption due to kidney dysfunction; the result is a reduction in both bone mineral density and quality. This condition is compounded by disruption of bone metabolic turnover, abnormalities in bone microstructure and collagen cross-linking, and compromised bone quality, all of which contribute to increased bone fragility. Reduced kidney function is complicated by secondary hyperparathyroidism, which exacerbates bone fragility. Managing osteoporosis in patients with CKD is chal

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… (2) Active vitamin D preparations (alfacalcidol, calcitriol, eldecalcitol) Active vitamin D preparations such as alfacalcidol and calcitriol promote calcium absorption by the intestine, suppress PTH secretion from parathyroid glands, and attenuate skeletal resistance to the effects of PTH, leading … For such reasons, KDIGO do not recommend routine use of calcitriol and vitamin D analogs among CKD G3a–G5 [ 11 ]. …

Lambda light chain-induced monoclonal gammopathy of renal significance, manifesting with Fanconi Syndrome and osteomalacia.

BACKGROUND: Monoclonal gammopathy of renal significance (MGRS) encompasses a heterogeneous group of kidney diseases in which a monoclonal immunoglobulin secreted by a clone of B cells or plasma cells causes kidney damage without meeting the hematological criteria for malignancy. Among the various forms of involvement, MGRS can manifest as a proximal tubule disorder, such as Fanconi syndrome (FS), characterized by urinary loss of phosphate, glucose, amino acids, uric acid and bicarbonate. Few cases of MGRS have been described in the literature, manifesting as FS and monoclonal production of lam

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… Serum calcium levels were normal but with an elevated alkaline phosphatase and a history of calcitriol replacement since admission to another institution (one year ago, calcitriol treatment was later suspended). The 1,25 dihydroxyvitamin-D was decreased and the viral serologies were negative. … Washington LC dos-Santos, MD, IGM-FIOCRUZ In view of the above findings, in the initial approach, replacement was started with potassium citrate 10 mEq 8/8 h, calcitriol 0.25 mg 12/12 h, phosphorus 100 mg 12/12 h, powdered bicarbonate two teaspoons 12/12 h and enalapril 5 mg/day. …

Effect of Early Administration of Vitamin D on Clinical Outcome in Critically Ill Sepsis Patients: A Randomized Placebo-controlled Trial.

BackgroundAdministration of vitamin D to unselected heterogeneous critically ill patients did not demonstrate outcome benefit. The current study was undertaken to identify if early administration of vitamin D can reduce intensive care unit (ICU) length of stay and improve clinical outcomes in critically ill patients with sepsis.MethodsThis single-center randomized double-blind placebo-controlled trial was done in the ICU and emergency inpatient ward of a tertiary care teaching institute in New Delhi, India. A total of 126 adult patients aged 18 to 80 years of either sex diagnosed to have sepsi

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… In a prior RCT conducted in critically ill sepsis patients, administration of single-dose intravenous calcitriol 2 µg had mixed effects on markers of inflammation and innate immunity. 9 However, it was a small study conducted in 67 patients only and calcitriol was not administered early. … Randomized controlled trial of calcitriol in severe sepsis. Am J Respir Crit Care Med. 2014;190(5):533–541. doi: 10.1164/rccm.201405-0988OC. 10. Yadav S, Joshi P, Dahiya U, Baidya DK, Goswami R, Guleria R, et al. …

Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.

BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements. CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring d

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… The hypocalcemia improved with calcium supplementation (up to 9 g/day) and calcitriol (1.5 μg/day). She had a positive response to letrozole monotherapy for 4 months followed by fulvestrant for 3 months. … In both cases, hypocalcemia improved within a few days with calcium supplements (calcium lactate 3–15 g/day, calcium gluconate infusion 3.9–23.4 mEq/day) and vitamin D3 supplements (calcitriol 1.5 μg/day). …

Forestalling Hungry Bone Syndrome after Parathyroidectomy in Patients with Primary and Renal Hyperparathyroidism.

UNLABELLED: Hungry bone syndrome (HBS), severe hypocalcemia following parathyroidectomy (PTX) due to rapid drop of PTH (parathormone) after … ration (up to 30) requiring prompt intravenous calcium (Ca) intervention and vitamin D (VD) (mostly calcitriol) replacement. Hypophosphatemia and hypomagnesiemia may be found. RP: mildly/asymptomatic hypocalcemia controlled under oral Ca+VD for maximum 12 months (protracted HBS is up to 42 months). RHPT associates a higher risk of developing HBS as compared …

Vitamin D supplementation for chronic liver diseases in adults.

BACKGROUND: Vitamin D deficiency is often reported in people with chronic liver diseases. Improving vitamin D status could therefore be bene … D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 27 randomised clinical trials with 1979 adult participants. This review …

The Conundrum of Medical Fracture Prevention in Chronic Kidney Disease-Summary of the Evidence and Pragmatic Clinical Guidance.

Fragility fractures are a major complication in chronic kidney disease (CKD), yet therapeutic strategies for their prevention remain highly controversial. The unique pathophysiology of CKD-mineral and bone disorder (CKD-MBD), coupled with the paucity of dedicated clinical trials, create substantial uncertainty regarding the efficacy and safety of medical interventions established in the general osteoporosis population. This review summarizes the available evidence regarding fracture risk and bone mineral density including pragmatic clinical guidance for the use of calcium, vitamin D, phosphate

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… A cross-sectional study from Italy (n = 387) found an association between oral calcitriol intake and fracture prevalence (OR 0.6 [95% CI, 0.36–0.99]; p = 0.043) [ 56 ]. … Bone turnover markers declined (unspecified), and calcium remained stable with calcitriol doses only modestly increased (1.5 to 1.83 µg/week) [ 91 ]. …

Epidemiology of Tumor-Induced Osteomalacia in Germany Based on Real World Data.

Tumor-induced osteomalacia (TIO) is an ultra-rare disease caused mostly by benign tumors that secrete fibroblast growth factor-23. Because of nonspecific symptoms, the diagnostic delay is long, and therapy can be challenging. Moreover, epidemiological data on TIO are scarce owing to its rarity. Therefore, this study aimed to quantify TIO's incidence rates and prevalence in Germany. Retrospective longitudinal and cross-sectional analyses were conducted using anonymized German claims data from the statutory health insurance (SHI) database. This database, which comprises the data of approximately

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… In addition, FGF23 represses calcitriol activation by inhibiting the transcription of the enzyme, 1-α-hydroxylase (CYP27B1) and stimulating the expression of 24-α-hydroxylase (CYP24A1), thereby promoting calcitriol catabolism. … Table 2 Definition of the surrogates Surrogate | Definition Advanced imaging | PET, PET/CT, SPECT, SPECT/CT, EBT, scintigraphy Medication | alfacalcidol, calcitriol, phosphate, calcium Tumor removal | surgical tumor removal, radiotherapy Laboratory intervention | Calcium, Phosphate, AP, Gamma GT, CRP …

Bone Metabolism Effects of Medical Therapy in Advanced Renal Cell Carcinoma.

The medical therapy of advanced renal cell carcinoma (RCC) is based on the use of targeted therapies, such as tyrosine kinase inhibitors (TKI) and immune-checkpoint inhibitors (ICI). These therapies are characterized by multiple endocrine adverse events, but the effect on the bone is still less known. Relatively few case reports or small case series have been specifically focused on TKI and ICI effects on bone metabolism. However, the importance to consider these possible side effects is easily intuitable because the bone is one of the most frequent metastatic sites of RCC. Among TKI used in R

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… Elevated calcitriol level (142 pg/mL) and low parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) have been detected, suggesting that the hypercalcemia has been mediated by the elevation of calcitriol levels. … In the presence of hypocalcemia, treatment with intravenous calcium gluconate and oral calcitriol is suggested [ 123 ]. Calcitriol, the hormonally active synthetic vitamin D, represents the therapeutic gold standard of hypocalcemia in patients with chronic kidney disease. …

European guidance for the diagnosis and management of osteoporosis in postmenopausal women.

UnlabelledGuidance is provided in a European setting on the assessment and treatment of postmenopausal women with or at risk from osteoporosis.IntroductionThe European Foundation for Osteoporosis and Bone disease (subsequently the International Osteoporosis Foundation) published guidelines for the diagnosis and management of osteoporosis in 1997. This manuscript updates these in a European setting.MethodsThe following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of oste

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… Vitamin D derivatives Alfacalcidol is a synthetic analogue of the vitamin D metabolite calcitriol (1,25-dihydroxyvitamin D 3 ) and it is metabolised to calcitriol by its 25-hydroxylation in the liver. It is somewhat less potent than calcitriol. … Both alfacalcidol and calcitriol are used in some countries for the treatment of osteoporosis. Several but not all studies show decreases in vertebral fracture risk [ 92 – 94 ]. The effects on BMD have been less extensively studied. …