Hypercalcemia

Evaluation: 

• verify with repeat measurement that there is a true increase in the serum calcium concentration (total calcium corrected for albumin or ionized calcium) 
• Compare with previous values if available
• Clinical evaluation, including duration of hypercalcemia, presence or absence of symptoms, family history, and medications, may help determine the etiology of hypercalcemia

Causes:

• primary hyperparathyroidism
• malignancy (PTH related peptide, ectopic production of 1,25, dihydroxyvitamin D, osteoclast activating factor
•  lytic bone mets
• non parathyroid endocrine disorder
• thyrotoxicosis, pheochromocytoma, adrenal insufficiency, VIP-producing tumor
• granulomatous disease (1,25 dihydroxyvitamin D excess)
• sarcoidosis, tuberculosis, histoplasmosis, coccidiomycosis, leprosy
• medications (thiazide diuretics, lithium, estrogens, antiestrogens)
• milk-alkali syndrome
• vitamin A or D intoxication
• familial hypocalciuric hypercalcemia
• immobilization
• parenteral nutrition
• acute and chronic renal failure

Signs:

• "Stones, moans, groans, with psychic overtones*.
• Renal: polyuria (nephrogenic DI), nephrolithiasis, renal failure, ectopic calcification
• Gl: anorexia, nausea, vomiting, constipation
• Neuro: weakness, fatigue, confusion, stupor, coma
• ECG: Shortened QT

Treatment:

• avoid factors that can aggravate hypercalcemia, including thiazide diuretics and lithium carbonate therapy, volume depletion, prolonged bed rest or inactivity, calcium and/or vitamin D supplements, and a high-calcium diet (>1000 mg/day)
• Mild hypercalcemia - asymptomatic or  mildly symptomatic with with serum calcium level of 12 and 14 mg/dL [3 to 3.5 mmol/L]) may not require immediate therapy

• Moderate hypercalcemia - Asymptomatic or mildly symptomatic individuals with chronic moderate hypercalcemia (calcium between 12 and 14 mg/dL [3 to 3.5 mmol/L]) may not require immediate therapy
• Severe hypercalcemia - serum calcium levels of  >14 mg/dL [3.5 mmol/L]) or symptomatic (eg, lethargy, stupor) require aggressive therapy. 

• → Initial therapy of severe hypercalcemia includes the simultaneous administration of intravenous (IV) isotonic saline, subcutaneous calcitonin, and a bisphosphonate (typically, IV zoledronic acid)
• Correct dehydration, increase renal calcium excretion, decrease bone resorption, and treat the underlying disorder.

1. IV hydration, initial rate is 200 to 300 mL/hour that is then adjusted to maintain the urine output at 100 to 150 mL/hour
2. In individuals with renal insufficiency or heart failure, careful monitoring and judicious use of loop diuretics (after intravascular volume has been repleted) may be required to prevent fluid overload. IV furosemide
3. Specific treatment in approximate desirability of use:

• For immediate, short-term management in severe hypercalcemia (Ca >14 mg/dl)  and symptomatic patients (lethargy, stupor), administer Calcitonin in combination with NS hydration and Bisphosphonates. Initial Calcitonin dose is 4 units/kg, administered SQ or IM. Repeat serum calcium in 4-6 hrs. If lowering of calcium levels is noted, continue 4 U/kg BID for 24-48 hrs. May increase to 8 U/kg Q12H or Q6H for 24-48 hrs if response is not satisfactory with 4 U/kg BID. 
• Among IV bisphosphonates, Zaldronic Acidis preferred over pamidronate (60 to 90 mg over 2 hours) because it is superior to pamidronate in reversing hypercalcemia related to malignancy. The initial dose is 4 mg IV over 15 minutes.
• Pamidronate 15-45 mg IV as single IV infusion or 90 mg over 2-24 hours would be another option for treatment

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