Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report deals with a young man having prolonged fever presenting with hypercalcaemic crisis. Subsequent investigations confirmed tuberculosis (TB) peritonitis in the absence of pulmonary involvement as the cause of his symptoms. His hypercalcaemia and fever resolved with anti-TB therapy. Abdominal TB needs to be included in the differential diagnosis of otherwise unexplained hypercalcaemia especially in our region where TB is an endemic problem and is treatable.
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PMID:Hypercalcaemic crisis as the presenting manifestation of abdominal tuberculosis: a case report. 1097 90

Chronic renal failure is characterized by diminished synthesis of, and resistance to, the active vitamin D metabolite 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3, calcitriol). Calcitriol results from the biotransformation of the precursor 25-hydroxy-vitamin D3 (25(OH)D3) to 1,25(OH)2D3. 25(OH)D3 is synthesized in the liver, and 1alpha-hydroxylase, the rate-limiting enzyme for its biotransformation into the most active metabolite, 1,25(OH)2D3, is located in the kidney. The regulation of 1alpha-hydroxylase in renal failure is not well known. Recent work indicates that, in contrast to previous opinion, 1alpha-hydroxylase is predominantly expressed not in the proximal tubule but in the distal tubule [1]. In vivo, the main stimulatory signal is presumably parathyroid hormone (PTH) and the main inhibitory signal hyperphosphataemia. Both signals are altered in renal failure. There is also evidence that the renal 1alpha-hydroxylase becomes substrate-dependent in patients with renal failure. This means that a higher concentration of the precursor 25(OH)2D3 will result in a higher rate of transformation into the active metabolite 1,25(OH)2D3 in renal patients. Calcitriol is not exclusively synthesized in the kidney, but may also be synthesized in extra-renal tissues, e.g. activated monocytes/macrophages [2], particularly in granuloma [3] as shown by anephric uraemic patients who develop hypercalcaemia and elevated calcitriol concentrations when sarcoidosis [4] or tuberculosis [5] supervenes. On the other hand, calcitriol is less effective in uraemia. This may be to some extent due to diminished expression of vitamin D receptors [6], particularly in parathyroid glands when they undergo nodular transformation [7], but there may also be resistance to calcitriol at the post-receptor level [8]. In a series of elegant experiments [9,10], calcitriol resistance has been related to disturbed genomic effects of active vitamin D because the interaction of the vitamin D receptor ligand complex with vitamin D-responsive elements (VDREs) upstream of vitamin D-regulated genes was disturbed by the action of low molecular weight substances in uraemia, which have not been completely characterized. The role of genetically determined polymorphisms of the vitamin D receptor in the genesis of disturbed calcium metabolism of renal failure is currently unclear.
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PMID:Management of disturbed calcium metabolism in uraemic patients: 1. Use of vitamin D metabolites. 1107 70

We describe a female patient undergoing hemodialysis who developed tuberculosis, hypercalcemia, and inappropriately elevated calcitriol levels. These findings suggest ectopic production of calcitriol by tuberculous granulomas. Successful treatment of tuberculosis led to a substantial decrease in the levels of calcium and calcitriol.
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PMID:Hypercalcemia, inappropriate calcitriol levels, and tuberculosis on hemodialysis. 1109 92

Hypercalcemia is associated with numerous chronic granulomatous processes and chronic infections. Increased production of calcitriol by activated macrophages has been shown to be the cause in most cases. In this article, we describe three cases of hypercalcemia associated with inappropriately elevated calcitriol levels and suppressed PTH in hemodialysis. In addition to conventional techniques for tuberculosis diagnosis we used Ligase Chain Reaction (LCR) to detect mycobacterial DNA in pleural effusion with acid-fast stain and culture negativity. Antituberculous therapy was associated with a decrease in the levels of calcium, as well as in serum calcitriol concentrations, and a substantial increase in the levels of iPTH. The serum levels of 25(OH)D3 remained unchanged. These findings suggested ectopic production of calcitriol. The discussion reviews the previously reported cases of hypercalcemia and tuberculosis that occurred during hemodialysis, and concludes that ectopic production of calcitriol by tuberculous granulomas is extremely unusual and its demonstration requires a high index of suspicion. Molecular techniques are a potentially useful approach for early and rapid diagnosis of tuberculous infection in dialysis patients.
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PMID:[Association of hypercalcemia, elevated levels of calcitriol and tuberculosis in patients on hemodialysis]. 1110 Jun 67

Hypercalcaemia has been known to occur in association with granulomatous diseases. The aim of this study was to ascertain the incidence of hypercalcaemia and determine the prevalence of symptoms associated with it in Greek patients with newly-diagnosed tuberculosis (TB), before the initiation of anti-tuberculosis treatment. We prospectively evaluated all patients with newly-diagnosed TB presenting, either as inpatients or as outpatients, to our hospital, during a 3-year period. We evaluated 88 patients with TB (50 males and 38 females), aged between 23 and 89 years (mean age+/-SD: 46.4+/-19 years), and 65 age- and sex-matched controls with chronic obstructive pulmonary disease (36 males and 29 females), aged between 28 and 88 years (mean age+/-SD: 47.2+/-18 years). Among TB patients, 56 had pulmonary TB, 20 had pleural TB without evidence of pulmonary parenchyma involvement, eight had pulmonary and pleural TB, and four had disseminated disease. The mean (+/-SD) albumin-adjusted serum calcium concentration and the mean ionized calcium concentration were significantly higher in the TB group (2.49+/-0.21 mmol l(-1) and 1.27+/-0.02 mmol l(-1) respectively) than in the control group (2.36+/-0.11 mmol l(-1) and 1.19+/-0.02 mmol l(-1), P<0.05). In the TB group no correlation between type of disease and albumin-adjusted or ionized calcium concentration was seen. Hypercalcaemia was detected in 22 patients with TB (25%) but only three showed symptoms associated with it. We conclude that, although hypercalcaemia is a common laboratory finding among Greek patients with TB before anti-TB chemotherapy, it is usually asymtomatic.
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PMID:Hypercalcaemia in Greek patients with tuberculosis before the initiation of anti-tuberculosis treatment. 1126 35

Hypercalcaemia may complicate granulomatous diseases, such as tuberculosis and sarcoidosis, and various AIDS-related opportunistic infections and malignancies. We report here two patients with AIDS and disseminated Mycobacterium avium infection who developed symptomatic hypercalcaemia several weeks after commencing antimycobacterial chemotherapy, and in whom inappropriately elevated 1,25(OH)(2)D(3)levels were documented. Although vitamin D supplementation may have contributed, no other cause for the hypercalcaemia was found. The biochemical and clinical similarities between these cases and other hypercalcaemic granulomatous diseases suggest a common mechanism related to macrophage activation and dysregulated vitamin D production.
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PMID:Hypercalcaemia and elevated 1,25(OH)(2)D(3) levels associated with disseminated Mycobacterium avium infection in AIDS. 1153 24

The cytokine gamma interferon (IFN-gamma) and the calcitropic steroid hormone 1,25-dihydroxyvitamin D (1,25D) are activators of macrophage immune function. In sarcoidosis, tuberculosis, and several granulomatoses, IFN-gamma induces 1,25D synthesis by macrophages and inhibits 1,25D induction of 24-hydroxylase, a key enzyme in 1,25D inactivation, causing high levels of 1,25D in serum and hypercalcemia. This study delineates IFN-gamma-1,25D cross talk in human monocytes-macrophages. Nuclear accumulation of Stat1 and vitamin D receptor (VDR) by IFN-gamma and 1,25D promotes protein-protein interactions between Stat1 and the DNA binding domain of the VDR. This prevents VDR-retinoid X receptor (RXR) binding to the vitamin D-responsive element, thus diverting the VDR from its normal genomic target on the 24-hydroxylase promoter and antagonizing 1,25D-VDR transactivation of this gene. In contrast, 1,25D enhances IFN-gamma action. Stat1-VDR interactions, by preventing Stat1 deactivation by tyrosine dephosphorylation, cooperate with IFN-gamma/Stat1-induced transcription. This novel 1,25D-IFN-gamma cross talk explains the pathogenesis of abnormal 1,25D homeostasis in granulomatous processes and provides new insights into 1,25D immunomodulatory properties.
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PMID:Stat1-vitamin D receptor interactions antagonize 1,25-dihydroxyvitamin D transcriptional activity and enhance stat1-mediated transcription. 1190 70

A 54 year old man presented with frontal headaches for one year. A CT scan of the head revealed a pituitary mass. He denied a change in vision or galactorrhea, but did have decreased frequency of erections and a recent episode of renal stones. On physical exam, the cranial nerves were normal. Visual field exam revealed mild bilateral temporal defects. The genitalia were normal and the testes were soft. Laboratory evaluation revealed: Na, 134 mM/l; K, 6.7 mM/l; Cl, 104 mM/l; HCO3, 22 mM/l; BUN, 47 mg/dl; Cr, 8.3 mg/dl; Ca, 12.5 mg/dl; Phos, 5.5 mg/dl; prolactin, 32.0 ng/ml; T4, 4.46 microg/dl; TSH, 2.07 microU/ml; LH, 18.1 mIU/ml; FSH 3.2 mIU/ml; alpha subunit 1.6 ng/ml; testosterone 255 ng/dl; cortisol, 20.3 microg/dl; cortisol after 250 microg cortrosyn, 38.5 microg/dl (time 60 minutes); growth hormone, 1.4 ng/ml; IGF-1, 47 ng/ml; PTH, <1 pg/ml; 25-hydroxyvitamin D, 14 ng/ml; 1,25-dihydroxyvitamin D, 69 pg/ml. These results were felt to be consistent with a non-PTH-mediated hypercalcemia, such as humoral hypercalcemia of malignancy, or a vitamin D-mediated hypercalcemia, such as lymphoma, sarcoidosis or tuberculosis. Head MRI demonstrated a 3.5 x 3.5 x 2.5 cm heterogeneous mass enlarging the sella, deforming the clivus and compressing the cavernous sinus, basilar artery and left side of the optic chiasm. There was a small focus of high signal in the superior part of the mass on the T1-weighted image from either a proteinaceous cyst with early calcium deposition or sub-acute blood. These radiographic findings were felt to be consistent with a pituitary adenoma. The patient was treated with intravenous hydration and thyroxine 50 microg daily and underwent a transsphenoidal resection of the pituitary lesion. Pathologic examination revealed a pituitary adenoma with multiple granulomas and crystalline material; this was consistent with sarcoid within the adenoma. Post-operatively, the serum LH fell to 5.5 mIU/ml. A subsequent transbronchial biopsy revealed multiple non-caseating granulomas. A serum ACE level was elevated at 132.6 U/l. He received oral prednisone 60 mg daily with resolution of the hypercalcemia. Neurosarcoidosis occurs in 5 to 15% of patients with sarcoidosis and can involve the hypothalamus and pituitary gland. This is the first reported case of sarcoidosis occurring within a pituitary adenoma.
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PMID:Sarcoidosis within a pituitary adenoma. 1213 93

Hypercalcemia is a common electrolyte disturbance in chronic dialysis patients. Although most causes are easily identified, some are obscure. Tuberculosis, a granulomatous disease associated with hypercalcemia, can appear at anytime while the infection is active. Dialysis-associated tuberculosis is characterized by a higher risk than that in the general population, with a greater chance of extrapulmonary involvement and a high mortality rate. If the presentation of tuberculosis is atypical and its manifestation nonspecific, diagnosis can be delayed, leading to poor patient outcome. Herein, we report a case of tuberculous peritonitis in a hemodialysis patient. Asymptomatic hypercalcemia was noted 8 months before ascites became detectable. Nevertheless, the patient responded well to antituberculous therapy. We conclude that hypercalcemia can be an early sign of tuberculous peritonitis in the absence of other signs and symptoms. Remaining aware of the possibility of tuberculosis and testing for it, physicians can identify tuberculous infection earlier and initiate appropriate therapy in a timely manner.
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PMID:Chronic hypercalcemia as the presenting feature of tuberculous peritonitis in a hemodialysis patient. 1238 58

We report on a female infant with disseminated tuberculosis who presented with clinical sepsis and disseminated intravascular coagulation starting at 14 days of age. Parenteral ofloxacin combined with streptomycin were used because the enteral route was not possible and intravenous isoniazid and rifampicin were not available. Rare complications including infection-associated hemophagocytic syndrome, hypercalcemia, and adrenal insufficiency were detected and successfully managed.
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PMID:Neonatal tuberculosis associated with shock, disseminated intravascular coagulation, hemophagocytic syndrome, and hypercalcemia: a case report. 1255 35


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