Chapter 047. Hypercalcemia and Hypocalcemia (Part 3)

A detailed history may provide important clues regarding the etiology of the hypercalcemia (Table 47-1). Chronic hypercalcemia is most commonly caused by primary hyperparathyroidism, as opposed to the second most common etiology of hypercalcemia, an underlying malignancy. The history should include medication use, previous neck surgery, and systemic symptoms suggestive of sarcoidosis or lymphoma.Once true hypercalcemia is established, the second most important laboratory test in the diagnostic evaluation is a PTH level using a two-site assay for the intact hormone. Increases in PTH are often accompanied by hypophosphatemia. In addition, serum creatinine should be measured to assessrenal function; hypercalcemia...
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Chapter 047. Hypercalcemia and Hypocalcemia (Part 3) Chapter 047. Hypercalcemia and Hypocalcemia (Part 3) A detailed history may provide important clues regarding the etiology ofthe hypercalcemia (Table 47-1). Chronic hypercalcemia is most commonly causedby primary hyperparathyroidism, as opposed to the second most common etiologyof hypercalcemia, an underlying malignancy. The history should includemedication use, previous neck surgery, and systemic symptoms suggestive ofsarcoidosis or lymphoma. Once true hypercalcemia is established, the second most importantlaboratory test in the diagnostic evaluation is a PTH level using a two-site assayfor the intact hormone. Increases in PTH are often accompanied byhypophosphatemia. In addition, serum creatinine should be measured to assessrenal function; hypercalcemia may impair renal function, and renal clearance ofPTH may be altered depending on the fragments detected by the assay. If the PTHlevel is increased (or inappropriately normal) in the setting of an elevatedcalcium and low phosphorus, the diagnosis is almost always primaryhyperparathyroidism. Since individuals with familial hypocalciuric hypercalcemia(FHH) may also present with mildly elevated PTH levels and hypercalcemia, thisdiagnosis should be considered and excluded because parathyroid surgery isineffective in this condition. A calcium/creatinine clearance ratio (calculated asurine calcium/serum calcium divided by urine creatinine/serum creatinine) of Mild, asymptomatic hypercalcemia does not require immediate therapy,and management should be dictated by the underlying diagnosis. By contrast,significant, symptomatic hypercalcemia usually requires therapeutic interventionindependent of the etiology of hypercalcemia. Initial therapy of significanthypercalcemia begins with volume expansion since hypercalcemia invariablyleads to dehydration; 4–6 L of intravenous saline may be required over the first 24h, keeping in mind that underlying comorbidities (e.g., congestive heart failure)may require the use of loop diuretics to enhance sodium and calcium excretion.However, loop diuretics should not be initiated until the volume status has beenrestored to normal. If there is increased calcium mobilization from bone (as inmalignancy or severe hyperparathyroidism), drugs that inhibit bone resorptionshould be considered. Zoledronic acid (e.g., 4 mg intravenously over ~30 min),pamidronate (e.g., 60–90 mg intravenously over 2–4 h), and etidronate (e.g., 7.5mg/kg per day for 3–7 consecutive days) are approved by the U.S. Food and DrugAdministration for the treatment of hypercalcemia of malignancy in adults. Onsetof action is within 1–3 days, with normalization of serum calcium levels occurringin 60–90% of patients. Bisphosphonate infusions may need to be repeated ifhypercalcemia relapses. Because of their effectiveness, bisphosphonates havereplaced calcitonin or plicamycin, which are rarely used in current practice for themanagement of hypercalcemia. In rare instances, dialysis may be necessary.Finally, while intravenous phosphate chelates calcium and decreases serumcalcium levels, this therapy can be toxic because calcium-phosphate complexesmay deposit in tissues and cause extensive organ damage. In patients with 1,25(OH)2D-mediated hypercalcemia, glucocorticoids arethe preferred therapy, as they decrease 1,25(OH)2D production. Intravenoushydrocortisone (100–300 mg daily) or oral prednisone (40–60 mg daily) for 3–7days are used most often. Other drugs, such as ketoconazole, chloroquine, andhydroxychloroquine, may also decrease 1,25(OH)2D production and are usedoccasionally. HYPOCALCEMIA Etiology The causes of hypocalcemia can be differentiated according to whetherserum PTH levels are low (hypoparathyroidism) or high (secondaryhyperparathyroidism). Although there are many potential causes of hypocalcemia,impaired PTH or vitamin D production are the most common etiologies (Table 47-2) (Chap. 347). Because PTH is the main defense against hypocalcemia, disordersassociated with deficient PTH production or secretion may be associated withprofound, life-threatening hypocalcemia. In adults, hypoparathyroidism mostcommonly results from inadvertent damage to all four glands during thyroid orparathyroid gland surgery. Hypoparathyroidism is a cardinal feature ofautoimmune endocrinopathies (Chap. 345); rarely, it may be associated withinfiltrative diseases such as sarcoidosis. Impaired PTH secretion may besecondary to magnesium deficiency or to activating mutations in the CaSR, whichsuppress PTH, leading to effects that are opposite to those that occur in FHH.