Making The Diagnosis

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The development of first carboxyl and midterminal PTH assays and, subsequently, intact or two-site PTH

assays has made it considerably easier to diagnose patients with PHPT (Figure 5-5).10 PHPT is the most common cause of hypercalcemia in outpatients, whereas malignancy is the most common cause of hypercalcemia in hospitalized patients. These two conditions account for more than 90% of all patients with hypercalcemia. The differential diagnosis of hypercalcemia includes granulomatous diseases, most commonly sarcoidosis; increased consumption of calcium, vitamin D, vitamin A, and alkali; and other endocrinopathies such as hyperthyroidism, hypothy-roidism, vasoactive intestinal peptide-secreting tumor (VIPoma), Addison's disease, and pheochromocytoma (Table 5-2). Other causes are immobilization in patients with high turnover bone disease such as Paget's disease and BFHH. Very rarely, a nonparathy-roid malignant tumor secretes pure PTH.1112

Patients with documented hypercalcemia for more than 6 months do not have malignancy-associated hypercalcemia because patients with malignancy, unfortunately, do not live this long. Patients with hypercalcemia, hypercalciuria, and an elevated or inappropriately high PTH virtually all have PHPT. It is, therefore, no longer necessary to do excessive testing to rule out other causes of hypercalcemia to

Figure 5-4. Symptoms and physical findings of hyperparathyroidism.
Figure 5-5. Two-site antibody assay targeting the parathyroid hormone (PTH). An anti-PTH antibody is tagged to an acridium ester. Then an antibody-coated bead is added to the sample, creating a sandwich and activating the ester, which emits chemiluminescence and can be measured.

make an accurate diagnosis in hypercalcemic patients. Assessment of renal function, serum phosphorus and chloride, alkaline phosphatase, and uric acid levels, however, is helpful and can document mild renal tubular acidosis, renal dysfunction, high turnover bone disease with possible osteitis fibrosa cystica (Figure 5-6), and a predisposition to gout (Table 5-3). An elevated bone alkaline phosphatase will predict the need for calcium replacement owing to "bone hunger" in the postoperative period. Industrial-grade hand films can clarify the diagnosis in patients with an elevated alkaline phosphatase and often expedite therapy in patients with hypercalcemic crisis. Evidence of subperiosteal resorption in

VIPoma = vasoactive intestinal peptide-secreting tumor.

a hypercalcemic patient is diagnostic of hyper-parathyroidism so that one does not have to wait until the PTH level is available.

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