Findings of parathyroid surface proteins acting as calcium receptors have improved our understanding of the secretory dysfunctions leading to the hypercalcemia of HPT, and it is hoped that research on the regulation of function of these proteins will provide new treatments for HPT. The diagnosis of HPT has improved substantially since the introduction of sensitive and specific assays for the intact 84—amino acid peptide. Such immunoradiometric or immunochemolumi-nescent sandwich assays should accurately differentiate HPT from other causes of hypercalcemia. Moreover, these assays enable recognition of most patients with HPT, but their efficiency in this respect depends on applied criteria for biochemical recognition and operative confirmation of parathyroid disease.


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Diagnosis of Primary Hyperparathyroidism and Indications for Parathyroidectomy

Primary hyperparathyroidism is a relatively common problem, and reportedly 100,000 new cases are detected each year in the United States.1 One of every 500 women and 1 of every 2000 men older than 40 years have primary hyperparathyroidism. A population-based study in Sweden suggested that about 2% of postmenopausal women have hyperparathyroidism.2 The disease entities to be considered in the differential diagnosis of hypercalcemia are shown in Table 40-1. Primary hyperparathyroidism and malignancy account for 90% of all patients with hypercalcemia. Primary hyperparathyroidism is the most common cause of hypercalcemia in outpatients, whereas malignancy is the most common cause of hypercalcemia in hospitalized patients.3

Malignancy-associated hypercalcemia has traditionally been considered to include three distinct syndromes: (1) humoral hypercalcemia of malignancy, (2) hypercalcemia associated with bone metastases, and (3) hypercalcemia associated with hematologic malignancy (multiple myeloma). Humoral hypercalcemia of malignancy occurs in patients with solid tumors of the lung, breast, kidney, head and neck, and ovary without bone metastases and is known to be mediated primarily by parathyroid hormone-related peptide (PTHrP).4 A comparison of the biochemical characteristics of primary hyperparathyroidism and humoral hypercalcemia of malignancy is shown in Table 40-2. PTHrP also plays a role in the hypercalcemia associated with bone metastases5 and multiple myeloma.6 Interestingly, primary bone tumors such as osteogenic sarcoma seldom cause hypercalcemia.7

Primary hyperparathyroidism may be distinguished from the other causes of hypercalcemia by careful history, physical examination, and laboratory investigations.

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