Medical Care
Treatment depends on the severity of symptoms and the underlying cause. [24]
Volume depletion results from uncontrolled symptoms leading to decreased intake and enhanced renal sodium loss. This tends to exacerbate or perpetuate the hypercalcemia by increasing Na+ reabsorption in the thick ascending limb of the loop of Henle (TALH). Thus, appropriate volume repletion with isotonic sodium chloride solution is an effective short-term treatment for hypercalcemia. [25]
Once volume is restored, simultaneous administration of loop diuretics blocks Na+ and calcium reabsorption in the TALH. Replacing ongoing sodium, potassium, chloride, and magnesium losses is important if prolonged sodium chloride and loop diuretic therapy is contemplated.
Immobilization aggravates hypercalcemia. Whenever possible, weightbearing mobilization should be encouraged.
Reduction of dietary calcium and vitamin D intake is effective for treating hypercalcemia due to increased intestinal calcium absorption (eg, in idiopathic infantile hypercalcemia, ie, Williams syndrome). In vitamin D toxicity or extrarenal synthesis of 1,25(OH) D3 (eg, in sarcoidosis), prednisone may help reduce plasma calcium levels by reducing intestinal calcium absorption. Oral phosphate also can be used to form insoluble calcium phosphate in the gut.
Bisphosphonates inhibit osteoclastic bone resorption and are effective in the treatment of hypercalcemia due to conditions causing increased bone resorption and malignancy-related hypercalcemia. Pamidronate and etidronate can be given intravenously, while risedronate and alendronate may be effective as oral therapy. Calcitonin can be given intramuscularly or subcutaneously, but it becomes less effective after several days of use. Mithramycin blocks osteoclastic function and can be given for severe malignancy-related hypercalcemia. It has significant hepatic, renal, and marrow toxicity.
The US Food and Drug Administration (FDA) approved denosumab (Xgeva) for treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy in December 2014. [26] Approval was based on results from an open-label, single-arm study that enrolled patients with advanced cancer and persistent hypercalcemia after recent bisphosphonate treatment. The primary endpoint was the proportion of patients with a response, defined as albumin-corrected serum calcium (CSC) < 11.5 mg/dL (2.9 mmol/L.
The study achieved its primary endpoint with a response rate at day 10 of 63.6% in the 33 patients evaluated. The estimated median time to response (CSC < 11.5 mg/dL) was 9 days, and the median duration of response was 104 days. [27]
Peritoneal dialysis or hemodialysis against calcium-free or lower calcium concentration dialysate solution is highly effective in lowering plasma calcium levels.
Surgical Care
Surgical care is directed toward reversing the underlying cause of hypercalcemia or repairing the orthopedic damage, as follows [28, 29] :
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Prolonged hypercalcemia due to hyperparathyroidism may warrant surgical neck exploration and removal of one or more parathyroid glands; this is particularly appropriate if evidence of nephrolithiasis, osteoporosis, reduction of renal function, neuromuscular symptoms, or radiographic bone disease is present
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Hypercalcemia due to malignancy, especially a tumor that is producing parathyroid hormone – related peptide (PTHrP), may necessitate surgical resection of the tumor
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Orthopedic complications of prolonged hypercalcemia (eg, osteoporosis), complications of Paget disease, or complications of bony metastases may require orthopedic or neurosurgical intervention
Consultations
Consultation with a surgeon or orthopedist may be required, as indicated.
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Investigations flowchart.
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Vitamin D metabolism.
