1. Hypercalcemia B9402037 陳名揚

2. Etiology BONE RESORPTION CALCIUM ABSORPTION MISCELLANEOUS CAUSES

3. Bone resorption Primary hyperparathyroidism – > parathyroid adenoma (< 11 mg/dL ) Secondary and tertiary hyperparathyroidism – > chronic renal failure (Ca↓ P↑) Malignancy – many solid tumor or leukemia (> 13mg/dL) – metastasis  cytokine – non-metastasis  PTHrP (parathyroid hormone related peptide) – Lyphoma  calcidiol --> calcitriol (by macrophage) Thyrotoxicosis – Following correction of hyperthyroidism Other – Hypervitaminosis A, estrogen, immobilization

4. Calcium absorption Increased calcium intake – Chronic kidney disease – Milk alkali syndrome High intake of milk or CaCO 3 metabolic alkalosis, hypercalcemia, renal insufficiency Hypervitaminosis D

5. Treatment Ca < 12mg/dL  do not require immediate treatment 14 > Ca > 12mg/dL – Acute  aggressive therapy – Chronic, Well-tolerant  may not require immediate treatment Ca> 14 mg/dL  require treatment

6. treatment SALINE HYDRATION – Hypovolemia via vomiting BISPHOSPHONATES – Interfere with osteoclast-mediated bone resorption CALCITONIN GLUCOCORTICOIDS – decreasing calcitriol production (activated mononuclear cells) GALLIUM NITRATE – inhibition of an ATPase dependent proton pump on the osteoclast ruffled membrane OTHER THERAPY – Calcimimetics (activating calcium receptors) – Dialysis

7. InterventionMode of actionOnsetDuration Isotonic saline hydration Restoration of intravascular volume Increases urinary calcium excretion Hours During infusion Loop diuretics Increase urinary calcium excretion via inhibition of calcium reabsorption in the loop of Henle Hours During therapy Calcitonin Inhibits bone resorption via interference with osteoclast maturation Promotes urinary calcium excretion 4-6 hours 48 hours Bisphosphonates Inhibit bone resorption via interference with osteoclast recruitment and function 24-72 hours 2-4 weeks Glucocorticoids Decrease intestinal calcium absorption Decrease 1,25-dihydroxyvitamin D production by activated mononuclear cells in patients with granulomatous diseases or lymphoma 2-5 days Days to weeks Gallium nitrateInhibits osteoclast-mediated bone resorption 3-5 days 2 weeks Calcimimetics Calcium sensing receptor agonist, reduces PTH (parathyroid carcinoma, secondary hyperparathyroidism in CKD) 2-3 days During therapy DialysisLow or no calcium dialysateHours During treatment

8. Reference Uptodate