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Endocrinology and Metabolism Hypercalcemia and Hyperparathyroidism Diagnosis Primary hyperparathyroidism is the most common cause of hypercalcemia in outpatients. Hypercalcemia is often discovered incidentally. Less common presentations are kidney stones, osteoporosis, pancreatitis, and fractures (osteoporosis). Hypercalcemia may also occur with the use of lithium (PTH mediated) or thiazide diuretics (non-PTH mediated) and in the setting of excessive ingestion of vitamin D and calcium. Malignancy is the most common cause of hypercalcemia in hospitalized patients. Sarcoidosis may be associated with hypercalcemia (10'){, of patients) and hypercalciuria (50'7, of patients) STUDY TABLE: Causes of Hypercalcemia Diagnosis Key features include hypercalcemia and... Primary hyperparathyroidism PTH elevated (80%) or inappropriately normal (207o); phosphorus low X-rays may show chondrocalcinosis or osteitis fibrosa cystica (rare) Humoral hypercalcemia of PTH suppressed; phosphorus normal or low malignancy PTH-related protein may be elevated but is not needed for diagnosis Local osteolytic lesions PTH suppressed; phosphorus normal or low Lytic bone metastases result in increased mobilization of calcium from the bone Multiple myeloma PTH suppressed; phosphorus elevated Look for patients presenting with new kidney injury and anemia Diagnose with serum and urine protein immunoelectrophoresis Granulomatous disease PTH suppressed; phosphorus elevated; calcitriol elevated (sarcoidosis and TB) and B-cell lymphoma Milk-alkali syndrome PTH suppressed; phosphorus, creatinine, carbon dioxide elevated Consider in healthy persons in whom primary hyperparathyroidism has been excluded Excessive ingestion of calcium carbonate to treat/prevent osteoporosis Hyperthyroidism Hypercalcemia is a frequent incidentalfinding in hyperthyroidism caused by direct stimulation of osteoclasts by thyroid hormone

Consider in healthy persons in whom primary hyperparathyroidism has been excluded Excessive ingestion of calcium carbonate to treat/prevent osteoporosis Hyperthyroidism Hypercalcemia is a frequent incidentalfinding in hyperthyroidism caused by direct stimulation of osteoclasts by thyroid hormone Hypercalcemia requiring acute intervention is most often associated with a rapid rise in serum calcium level and serum calcium >14 mg/dl. Symptoms may include change in mental status and coma. It is most common in the setting of malignancy. Testing If hypercalcemia is confirmed, check PTH, phosphate, creatinine, and 2S-hydrory.vitamin D levels. If PTH is elevated or inap propriately normal in the setting of elevated serum calcium, the most likely cause is primary hyperparathyroidism. DON'T BE TRICKED . In patients with hypercalcemia and normal PTH levels, measure urinary calcium excretion to exclude familial hypocalciuric hypercalcemia. If hyperparathyroidism is confirmed and surgery is indicated, imaging may be indicated (ultrasound, sestamibi scan, CT, MRI) Primary hyperparathyroidism is the most common manifestation of MEN1. 74