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Query: UMLS:C0020437 (hypercalcemia)
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The number of newly diagnosed cases of multiple myeloma in the Czech Republic is about 3-4 per 100 000 persons per year. In the higher age groups, the incidence increases. Multiple myeloma is an illness that reacts well to treatment which can result in periods of remission lasting for years. Some of the patients are even able to return to work. A pre-requisite for successful treatment is early diagnosis and this is usually in the hands of first line physicians. This is the reason why the Czech Myeloma Group, in conjunction with neurologists, orthopedicians and radio diagnosticians has issued the following recommendations for first line physicians containing a more detailed description of the symptoms and the diagnostic pitfalls of the disease. This disease reminds a chameleon for the variety of its symptoms. For the sake of clarification, we shall divide multiple myeloma symptoms into five points, each of which is reason enough to warrant an examination to confirm or rule out a malignant cause of health problems (a negative result does not automatically mean exclusion). If any of the recommended examinations results positive, the diagnostic process must be continued, in which case a general practitioner refers the patient to a specialist health centre. Observing these recommendations should minimize the number of cases of late diagnosis. 1. Bone destruction symptoms. - Unexplained backache for more than one month in any part of spine even without nerve root irritability or without pain in other part of skeleton (ribs, hips, or long bones). - Pain at the beginning of myeloma disease is very similar to benigne common discopathy, however the intensity of backache is decreasing within one months in benigne disease. In the case of malignant process the intensity of bone pain is steadily increasing. - Immediate imaging and laboratory investigation are indicated by resting and night pain in spinal column or in any part of skeleton. - Backache with the sign of spinal cord or nerve compression should be sent for immediate X Ray, and focussed CT/MRI followed by acute surgery if needed. - Osteoporosis especially in men and premenopausal women. 2. Features of changed immunity or bone marrow function. Persistent and recurrent infection, typical is normochromic anaemia, with leucopenia and trombocytopenia. 3. Raised erythrocyte sedimentation rate even increase concentration of total plasma protein. 4. Impaired renal function. Increased level of creatinin or proteinuria, nephrotic syndrome with bilateral legs oedema. 5. Hypercalcemia with typical clinical symptoms (polyuria with dehydratation, constipation, nausea, low level conscience, coma). Every one from these points has to be reason for general medical doctor to start battery of tests: -X-ray of bones focused to painful area (mandatory before physiotherapy, local anaesthesia or other empiric therapy). If plain X-ray does not elucidate pain and symptoms are lasting more than one month, please consider all circumstances and results from laboratory investigation. This patient needs referral to the centre with MRI/CT facilities (CT or MRI is necessary investigation in case of nerve root or spine compression). -Investigation of erythrocyte sedimantion rate (high level of sedimentation of erythrocyte can indicate multiple myeloma). -Full blood count. -Basic biochemical investigation serum and urine: serum urea, creatinin, ionts including calcium, total protein, and albumin CRP (high concentration of total protein indicates myeloma, low level of albumin indicates general pathological process, similary increased concentration of fibrinogen, impaired renal function indicates myeloma kidney, however hypercalcemia is typical for highly aggressive myeloma). -Quantitative screening for IgG, IgM and IgA in serum (isolated raised level one of immunoglobulin with decreased level of the others indicates myeloma). -Common electrophoresis of serum is able to detect monoclonal immunoglobulin level at few gramm concentration. If all the laboratory investigation are in normal level the possibility that the current problems are multiple myeloma origine is smaller, but it does not exclude one of rare variant--non secretory myeloma (undifferentiated plasmocyt lost characteristic feature to produce monoclonal immunoglobulin). If any of tests indicate the possibility of myeloma, patient require urgent specialist referral to department with possibility to make diagnosis of malignant myeloma.
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PMID:[Recommendations for early identification of damage to the skeleton by malignant processes, and for early diagnosis of multiple myeloma]. 1817 27

Disorders of mineral and bone metabolism are prevalent in patients with chronic kidney disease (CKD). The recent National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend that blood calcium (Ca) be regularly measured in patients with stages 3 to 5 CKD. The Kidney Disease: Improving Global Outcomes (KDIGO) position states that the measurement of ionized Ca (iCa) is preferred and that if total Ca (tCa) concentration is used instead, then it should be adjusted in the setting of hypoalbuminemia. In 691 consecutive patients with stages 3 to 5 CKD, we compared the ability of noncorrected and albumin-corrected tCa concentration to identify low, normal, or high iCa concentration. The agreement between noncorrected or albumin-corrected tCa and iCa was only fair. The risk for underestimating ionized calcium was independently increased by a low total CO(2) concentration when either noncorrected or albumin-corrected Ca was used and by a low albumin concentration only when noncorrected tCa was used. The risk for overestimating iCa was increased by a low albumin concentration only when albumin-corrected Ca was used. In conclusion, albumin-corrected tCa does not predict iCa better than noncorrected tCa. Moreover, both noncorrected and albumin-corrected tCa concentrations poorly predict hypo- or hypercalcemia in patients with CKD.
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PMID:Pitfalls of measuring total blood calcium in patients with CKD. 1840 Sep 41

Nephrogenic systemic fibrosis (NSF) is a disease of thickened, hard, hyperpigmented skin lesions with or without systemic fibrosis occurring in patients with renal insufficiency and associated with the administration of gadolinium-containing contrast. The pathogenesis of this disease is unclear, and there is no definitive treatment. We describe a 71-yr-old patient with stable chronic lymphocytic leukemia (CLL), end-stage renal disease (ESRD), and NSF who presented with hypercalcemia in 2006. Before onset of renal insufficiency in 2002, serum calcium, phosphorus, and PTH levels were normal. In 2004, the patient began hemodialysis, and he was diagnosed with NSF in 2005, shortly after undergoing an MRI with gadolinium contrast administration. Over the next 6 mo, albumin-corrected serum total calcium levels rose from 9.9 to 13.1 mg/dl (normal range, 8.5-10.5 mg/dl) with normal serum phosphorus levels. On admission in September 2006, 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels were elevated at 130.7 pg/ml (normal range, 25.1-66.1 pg/ml). Biopsy of an NSF lesion showed increased 25-hydroxyvitamin D(3)-1-alpha hydroxylase (CYP27B1) immunostaining compared with the biopsy from a normal control. This is the first reported association of NSF with hypercalcemia caused by elevated 1,25(OH)(2)D levels. This metabolic disturbance should be sought in future cases to determine a connection between NSF, 1,25(OH)(2)D metabolism, and CYP27B1 activation in the skin, which may shed light on the pathogenesis of this unusual local and systemic fibrosing disorder.
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PMID:Hypercalcemia and overexpression of CYP27B1 in a patient with nephrogenic systemic fibrosis: clinical vignette and literature review. 1911 10

Direct measurement of serum-ionized calcium (Ca2+) is the best available method to assess 'true' calcemia because serum total calcium is confounded by serum proteins, mainly albumin. However, calculated surrogates for Ca2+, albumin-adjustment particularly, have been widely used in the literature despite their insufficiency to evaluate calcemic status accurately. Recently, a new formula, in which serum total protein instead of albumin is used for adjustment of total calcium, has been suggested for very old hospitalized patients. We compared these two surrogates for Ca2+ with the direct measurement in both frail bedridden inpatients and in a general aged population. Both surrogates were equally insufficient in detecting hypocalcemia in both patient groups. However, the sensitivity and specifity for detecting hypercalcemia by both surrogates were relatively high in the bedridden inpatients. Precise assessment of calcemic status is particularly needed in research and in detecting mild hypo- or hypercalcemia. However, the calculated surrogates for Ca2+ have consistently failed in accurate assessment of 'true' calcemia. Thus, the direct measurement of Ca2+ should be favored instead of readily available automated surrogates. Adjustments of calcium for albumin or total protein may be useful in clinical practice in excluding hypercalcemia in very old bedridden patients, only.
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PMID:Calculated serum calcium is an insufficient surrogate for measured ionized calcium. 1913 31

It is well recognized that patients with end stage renal diseases (ESRD) have hyper-plastic parathyroid glands. In most patients, a decrease in parathyroid hormone (PTH) occurs by about 1 year after renal transplantation. However, some renal transplant recipients continue to have elevated level of PTH. We prospectively evaluated 121 patients undergoing renal transplantation between August 2000 and 2002. The duration of dialysis, calcium (Ca), phosphorus (P), albumin, creatinine and iPTH levels were recorded prior to transplantation and three months and one year after transplantation. These 121 patients were on dialysis for an average period of 17.4 months prior to transplantation. An increase in the serum Ca and a decrease in serum P and iPTH level was seen in the patients after transplantation (P< 0.001). Hyperparathyroidism was in 12 (9.9%) and 7 (5.7%) patients three months and one year after transplantation respectively. Elderly patients and patients with longer duration on dialysis had an increased risk of developing post transplant hyperpara-thyroidism and hypercalcemia in the first year post transplant (P< 0.05). In conclusion age and duration on dialysis before transplantation seems to be important risk factors for post transplant hyperparathyroidism.
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PMID:Risk factors of post renal transplant hyperparathyroidism. 1958 96

Primary hyperparathyroidism (PHPT) is characterized by the autonomous production of parathyroid hormone (PTH), in which there is hypercalcemia or normal-high serum calcium levels, in the presence of elevated or inappropriately normal serum PTH concentrations. Exceptionally, in symptomatic patients, a diagnosis can be established on the basis of clinical data. PHPT must always be evaluated in patients with clinical histories of nephrolithiasis, nephrocalcinosis, osseous pain, subperiosteal resorption, and pathologic fractures, as well as in those with osteoporosis-osteopenia on dual-energy X-ray absorptiometry (DEXA), a personal history of neck irradiation, or a family history of multiple endocrine neoplasia syndrome (types 1 or 2). Diagnosis of PHPT is biochemical. Asymptomatic hypercalcemia (total serum calcium corrected by albumin), without guiding signs or symptoms, is the most frequent manifestation of the disease. For the differential diagnosis, PTH(1-84) must be measured, as well as phosphate, chloride, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and calcium-to-creatinine clearance. Suppressed or inappropriately low PTH1-84 guides the diagnose toward tumoral hypercalcemia and less frequently to granulomatous disease (sarcoidosis, tuberculosis, etc.), inadequate intake of 1alpha-hydroxyvitamin D or calcitriol, vitamin D or A intoxication, lithium intake, endocrinopathies (hyperthyroidism, Addison's disease, etc.) or treatment with thiazides, among other possibilities. Diagnosis of PHPT is confirmed by demonstrating persistent hypercalcemia (or normal-high serum calcium levels) in the presence of inappropriately normal or elevated serum PTH(1-84) concentrations, unless the urinary calcium-to-creatinine clearance ratio is lower than 0.01. In these cases, in the absence of thiazide intake or severe vitamin D deficiency, diagnosis should focus on benign familial hypercalcemic hypocalciuria. Parathyroid gland imaging is useful for localization of PHPT, but not for diagnosis of this entity.
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PMID:[Diagnostic evaluation and differential diagnosis of primary hyperparathyroidism]. 1962 56

It is often reminded that if the ionized calcium is not measured, the interpretation of total calcemia should consider serum albumin. Two formulas are usually employed: ["Corrected" Ca (mmol/L) = Ca measured (mmol/L) + 0.020 or 0.025 (40 - albumin (g/L))]. This adjustment formula arises from works of Payne published in 1973. In a control population, we established the median values of calcium, albumin and ionized calcium (corrected to pH 7.40), respectively 2.34 mmol/L, 45.7 g/L and 1.23 mmol/L with our laboratory's methods (albumin - bromocresol green and Ca - ortho-cresolphtalein on a Modular analyser, Roche Diagnostics; ionized calcium with ion-selective electrode, Radiometer SA). Based on this, we retrospectively compared for 71 patients who do not belong to the control population the "corrected calcium" resulting from the two formulas and the measured calcemia to the ionized calcium corrected at pH 7,40. This comparison shows that in our laboratory, the two formulas lead to a rising underestimation of the calcium for albumin values greater than 40 g/L, reaching -0,20 mmol/L for albumin values above 44 g/L. The use of this formulas may also mask an hypercalcemia, indeed half of our patients' hypercalcemia (ionised Ca ((pH 7,40)) > 1,29 mmol/L) is not found. These results agree with Payne's recommendations for the use of his adjustment formula: the clinically justified adjustment of a low calcemia due to an hypoalbuminemia should not be extended to other situations, particularly when albumin is increased.
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PMID:["Corrected" calcium: calcium status underestimation in non-hypoalbuminemic patients and in hypercalcemic patients]. 1965 80

The efficacy and safety of various modes of medical treatment for primary hyperparathyroidism (PHPT) in pregnancy is largely unknown. This report describes two cases of PHPT in pregnancy that were temporarily treated with the calcimimetic cinacalcet. The first case was diagnosed in the 31st week of pregnancy. The patient was asymptomatic and had an albumin-corrected total calcium level (Ca(corr)) of 3.24 mmol/l. As serum calcium was only mildly elevated it was decided to postpone surgery to the postpartum period. Cinacalcet was started immediately after delivery to prevent a postpartum surge in serum calcium. The second patient presented with hypertension and symptomatic hypercalcemia (Ca(corr) 3.96 mmol/l) in the 32nd week of pregnancy. Surgery was postponed because of suspected pheochromocytoma. Treatment with a combination of cinacalcet and calcitonin reduced serum Ca(corr) to 3.0 mmol/l. This report describes the monitoring of mother and child, and explores the pros and cons of the use of calcimimetics during pregnancy and puerperium.
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PMID:Cinacalcet for hyperparathyroidism in pregnancy and puerperium. 1984 25

Abnormalities in calcium concentration are frequent in patients receiving dialysis therapy. Most cases of both hypo- and hypercalcemia are mild and asymptomatic. There is concern, however, that, on the one hand, hypocalcemia can drive hyperparathyroidism and eventually lead to gland hypertrophy and autonomous function. Hypercalcemia, on the other hand, can be associated with increased extraosseous calcium and phosphate deposition leading to vascular calcification with an attendant mortality and morbidity. Calcium exists in three main forms in the blood: the physiologically active free or ionized fraction (terms often used interchangeably), a protein bound fraction, and a fraction complexed to other anions. Although the ionized calcium can readily be measured using ion-specific electrodes, it is the total calcium that is most commonly measured because of sample handling and cost concerns. As it is the free or ionized form that is biologically active (and therefore of most relevance), a number of adjustment formulae have been derived to "correct" the total calcium for changes in albumin, protein, and complexing ion concentrations. These formulae show good statistical correlation with measured ionized calcium in populations studied as a whole, but are generally poor predictors of true ionized hypo- or hypercalcemia in individual patients. International guideline committees in nephrology recommend frequent assessment of calcium levels in dialysis patients and recommend that these levels be kept within the normal reference range. These guidelines are less clear on which measurement of calcium should be used to guide clinical decision making. This review examines the merits of making any adjustment to the total calcium measurement, and suggests when it is appropriate to measure the ionized or free calcium.
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PMID:Is the calcium correct? Measuring serum calcium in dialysis patients. 2049 82

Vitamin D deficiency is prevalent among patients with end-stage organ failure awaiting transplant. Low serum 25-hydroxyvitamin D (25-OHD) levels in these patients may be related to many disease-specific factors, as well as decreased sunlight exposure and limited intake of foods containing vitamin D. Low serum 25-OHD levels are also extremely common following solid organ transplantation, both during the immediate postoperative period and in long-term graft recipients. Demographic and lifestyle factors are important in determining D status in transplant recipients. Worse vitamin D status is associated with poorer general health, lower albumin, and even decreased survival among these patients. Although several studies have demonstrated that active forms of vitamin D and its analogues prevent bone loss following transplantation, the data do not show consistent benefit. These therapies may have particular utility after renal transplantation. However, given the narrow therapeutic window with respect to hypercalcemia and hypercalciuria, and the demonstrated efficacy of bisphosphonates to prevent post-transplantation bone loss, we regard these agents as adjunctive rather than primary therapy for transplantation osteoporosis. The effects of 1,25(OH)(2)D on the immune system, which are still being elucidated, may have potential for reducing infections and preventing allograft rejection after transplantation.
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PMID:Vitamin D in organ transplantation. 2120 11


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