Calcium hypercalcemia

On the other hand, elevated blood levels of calcium (hypercalcemia) may promote irregular heartbeats, toxicity of cardiac drugs, and r deposits of the mineral in the arteries and kidneys. Hypercalcemia is not usually due to dietary calcium, but to such factors as an excess of vitamin D or a deficiency of magnesium. 

Calcitonin is secreted when abnormally high calcium levels occur in plasma. Although plasma concentrations are normally minute (<100 pg/mL), they increase two- to threefold after calcium infusion. Calcitonin has a short plasma half-life (ca 10 min). Certain thyroid tumors are the result of CT concentrations 50—500 times normal. The mechanism of action is a direct inhibition of bone resorption. Calcitonin is used clinically in various diseases in which hypercalcemia is present, eg, Paget s disease (46). 

The overall effect in most animals is to stimulate intestinal absorption of calcium with a concomitant increase in semm calcium and a reduction in parathyroid hormone (PTH). Modest hypercalcemia allows the glomerular filtration rate to remain stable and hypercalciuria to occur because of increased filtered load of calcium and reduction of tubular resorption of calcium with reduced PTH. However, with further increases in semm calcium, the glomerular filtration rate decreases, resulting in an even more rapid increase in semm calcium and the subsequent fall in urinary calcium. 

Vitamin D withdrawal is an obvious treatment for D toxicity (219). However, because of the 5—7 d half-life of plasma vitamin D and 20—30 d half-life of 25-hydroxy vitamin D, it may not be immediately successful. A prompt reduction in dietary calcium is also indicated to reduce hypercalcemia. Sodium phytate can aid in reducing intestinal calcium transport. Calcitonin glucagon and glucocorticoid therapy have also been reported to reduce semm calcium resulting from D intoxication (210). 

Calcium is readily abundant in the mammalian diet. A 70 kg human contains approximately 1200 g of calcium and has a daily intake of 1100 mg/day. There are no pubHshed exposure limits (38). Low levels of calcium in the blood, hypocalcemia, can lead to tetany high levels, hypercalcemia, can lead to coma and death. Calcium toxicity, above 160 mg/L in the blood, is not related to an excessive intake of calcium. 

The parathyroid glands in FHH are reset to maintain a higher than normal serum calcium concentration owing to impaired suppression of PTH release in the face of hypercalcemia (e.g., resistance to CaQ+) (Fig. 2). Similarly the kidneys show a reduced calciuric response to hypercalcemia, which contributes to the hypercalcemia by promoting inappropriately reabsorption of calcium. Mouse models of FHH and NSHPT result from targeted inactivation of one or both CaR alleles, respectively [1,3]. These animals have provided valuable insights into the alterations in tissue function resulting from loss of the receptor. 

Calcium-containing antacids—rebound hyperacidity, metabolic alkalosis, hypercalcemia, vomiting, confusion, headache, renal calculi, and neurologic impairment... 

Calcium is contraindicated in patients with hypercalcemia or ventricular fibrillation and in patients taking digitalis. Calcium is used cautiously in patients with cardiac disease. Hypercalcemia may occur when calcium is administered with the thiazide diuretics. When calcium is administered with atenolol there is a decrease in Hie effect of atenolol, possibly resulting in decreased beta blockade. There is an increased risk of digitalis toxicity when digitalis preparations are administered with calcium. The clinical effect of verapamil may be decreased when the drug is administered with calcium. Concurrent ingestion of spinach or cereal may decrease file absorption of calcium supplements. 

To combat this syndrome the physician may prescribe IV sodium chloride and a potent diuretic, such as furosemide. When used together these two drugs markedly increase calcium renal clearance and reduce hypercalcemia... 

Use calcium metabolism regulator (treatment of Paget s disease, hypercalcemia of malignancy)... 

May worsen hypercalcemia in hypovolemic patients by promoting tubular calcium reabsorption... 

Use in patients who have concomitant hypercalcemia and/or a calcium/phosphate product >55... 

Hypercalcemia is defined as a calcium concentration greater than 10.2 mg/dL (2.55 mmol/L). It maybe categorized as mild if total serum calcium is 10.3 to 12 mg/dL (2.575 to 3 mmol/L), moderate if total serum calcium is 12.1 to 13 mg/dL... 

Because the severity of symptoms and the absolute serum concentration are poorly correlated in some patients, institution of therapy should be dictated by the clinical scenario. All patients with hypercalcemia should be treated with aggressive rehydration normal saline at 200 to 300 mL/hour is a routine initial fluid prescription. For patients with mild hypocalcemia, hydration alone may provide adequate therapy. The moderate and severe forms of hypercalcemia are more likely to have significant manifestations and require prompt initiation of additional therapy. These patients may present with anorexia, confusion, and/or cardiac manifestations (bradycardia and arrhythmias with ECG changes). Total calcium concentrations greater than 13 mg/dL (3.25 mmol/L) are particularly worrisome, as these levels can unexpectedly precipitate acute renal failure, ventricular arrhythmias, and sudden death. 

A number of factors can limit calcium absorption, and special consideration must be given to calcium dosing to maximize absorption. Large amounts of calcium taken at once cannot be absorbed. Supplement doses should be limited to 500 to 600 mg of elemental calcium per dose. Calcium intake greater than 2500 mg/day should be avoided due to increased risk of toxicity, including hypercalciuria and hypercalcemia. 

Vitamin D is often combined in varying amounts with calcium salts. A multiple vitamin is another good source of vitamin D. Most multivitamins contain 400 IU per tablet. Vitamin D is also available as a single entity. Doses above 2000 IU/day should be avoided owing to the risk of hypercalciuria and hypercalcemia. Ergocalciferol (vitamin D2) and... 

The primary goal of treatment for hypercalcemia is to control the underlying malignancy. Therapies directed at lowering the calcium level are temporary measures that are useful until anticancer therapy begins to work. 

Therapeutic options for the treatment of hypercalcemia should be directed toward the level of corrected serum calcium and the presence of symptoms. Adequate treatment of mild or asymptomatic hypercalcemia may be achieved on an outpatient basis with nonpharmacologic measures. Moderate to severe or symptomatic hypercalcemia almost always requires pharmacologic intervention. 

The delicate balance maintained by these factors is altered in patients with cancer by two principal mechanisms tumor production of humoral factors that alter calcium metabolism (humoral hypercalcemia) and local osteolytic activity from bone metastases.27 Humoral hypercalcemia causes around 80% of all hypercalcemia cases and is mediated primarily by systemic secretion of parathyroid hormone-related protein... 

FIGURE 96-4. Pathophysiology of the hypercalcemia of malignancy. PTHrP, parathyroid hormone-related protein TGF-P, transforming growth factor P TNF-a, tumor necrosis factor alpha Ca2+, calcium IL-1, interleukin 1 IL-2, interleukin 2. 

What treatment plan would you outline to manage LP s hypercalcemia based on the calcium level and his signs and symptoms ... 

Therapeutic options for the treatment of hypercalcemia should be directed toward the level of corrected serum calcium and the presence of symptoms (Fig. 96-5). Hypercalcemia may be classified as mild [corrected calcium equal to 10.5-11.9 g/dL (2.6-3 mmol/L)], moderate [12-13.9 g/dL (3-3.5 mmol/L)], and severe [greater than 14 g/dL (3.5 mmol/L)].26 Adequate treatment of mild or asymptomatic hypercalcemia may be achieved on an outpatient basis with nonpharmacologic measures. Moderate to severe or symptomatic hypercalcemia almost always requires pharmacologic intervention. 

Multiple pharmacologic interventions are available for the treatment of hypercalcemia (Table 96-10). Furosemide 20 to 40 mg/day may be added to hydration once rehydration has been achieved to avoid fluid overload and enhance renal excretion of calcium. Although effective in relieving symptoms, hydration and diuretics are temporary measures that are useful until the onset of antiresorptive therapy thus hydration and antiresorptive therapy should be initiated simultaneously. 

Determine the status of the patient s underlying malignancy. Has this patient been treated for his or her underlying malignancy Has the patient received any prior therapy for hypercalcemia Is calcium-lowering therapy still warranted ... 

Counsel the patient to avoid excessive oral calcium intake in vitamin D-mediated hypercalcemia. 

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