syndrome, a genetic disorder of the PTH receptor, renders the receptor constitutively active Children with Jansen syndrome present with hypercalcemia, undetectable levels of PTH, and skeletal changes consistent with hyperparathyroidism Immobilization, particularly in rapidly growing adolescents, may result in significant bone resorption and hypercalcemia Malignancy is a rare cause of hypercalcemia in children Decreased renal excretion occurs in familial hypocalciuric hypercalcemia (FHH), an autosomal dominant disorder FHH is characterized by mild, asymptomatic hypercalcemia, increased tubular reabsorption of calcium, and inappropriately normal PTH Hypercalcemia may also be seen in patients with Williams syndrome, and several metabolic disorders including hypophosphatasia and Bartter syndrome Medications associated with hypercalcemia include thiazide diuretics and lithium The evaluation of hypercalcemia begins with a thorough assessment of symptoms, diet, medications, medical history, and family history Laboratory evaluation should include ionized calcium, electrolytes, phosphorus, magnesium, renal function, serum albumin, and acid–base assessment Review of previous laboratory studies, if available, should be performed Though results will not be available to the ED physicians, PTH level is critical to ultimately determine the underlying cause If the PTH is not elevated, vitamin D metabolites should be obtained Assessment of urine calcium excretion via random urine calcium to creatinine ratio may also be informative Calcium excretion is high in hyperparathyroidism but low in FHH and with thiazide therapy Clinical manifestations Hypercalcemia is associated with a number of signs and symptoms depending on the acuity and severity of the disorder Patients with mildly elevated calcium (less than 11.5 to 12 mg/dL) are often asymptomatic, especially if the elevation is chronic in onset Patients with moderate hypercalcemia (12 to 14 mg/dL) may experience anorexia, irritability, abdominal pain, constipation, and weakness An important renal manifestation of hypercalcemia is polyuria due to an inability to concentrate urine, an acquired form of nephrogenic diabetes insipidus Should polyuria be associated with gastrointestinal symptoms and decreased fluid intake, dehydration will ensue and aggravate the existing hypercalcemia by reducing renal excretion of calcium If hypercalcemia is severe, progressive weakness, confusion, seizures, and coma may develop