Urinary and Nephrogenous Adenosine 3′,5′-Monophosphate in the Hypercalcemia of Malignancy*

Abstract

Plasma cAMP concentration (PcAMP) and urinary cAMP excretion (UcAMP) were determined in 91 patients with hypercalcemia and malignancy, 15 patients with a malignancy and normal serum calcium concentrations, and 28 patients with primary hyperparathyroidism to assess its usefulness in the differential diagnosis of hypercalcemia. The patients with hypercalcemia and malignancy were subdivided into 2 groups: those with evidence of skeletal metastases and those without evidence of skeletal metastases (pseudohyperparathyroidism). In addition to cAMP determinations, serum immunoreactive parathyroid hormone (IPTH) and serum electrolytes were determined in all patients. PcAMP was elevated in both the cancer patients with hypercalcemia and those who were normocalcemic, but not in the patients with primary hyperparathyroidism. The mean UcAMP excretion was at least 2-fold elevated in all patient groups. Since nearly half of UcAMP is derived through the renal filtration of PcAMP, the nephrogenous component of cAMP excretion (NcAMP) was calculated. Despite the elevation of PcAMP, the mean NcAMP was also elevated in all cancer groups, although wide scatter in the results was seen. While NcAMP was commonly elevated in patients with pseudohyper parathyroidism (65%), 46% of the patients with hypercalcemia and malignancy with bone metastases and 60% of the patients with normocalcemia and malignancy also had increased levels of NcAMP. UcAMP and NcAMP were most likely to be elevated in patients with squamous cell carcinoma of the lung, esophagous, and oropharynx and hypernephromas, although increased values were found with all tumor types. Serum IPTH was elevated or inappropriately detectable in all patients with primary hyperparathyroidism. Only 4 of the 91 hypercalcemic malignancy patients had measurable serum IPTH concentrations, and 3 of these had evidence for coexistent primary hyperparathyroidism. Serum electrolytes in the hypercalcemic cancer patients with both bone metastases and pseudohyperparathyroidism showed a mild hypochloremic metabolic alkalosis suggestive of suppressed parathyroid hormone secretion. On the basis of these data, we conclude that a normal or increased level of UcAMP or NcAMP does not aid in differentiating hypercal-cemia secondary to parathyroid hormone excess from the nonparathyroid-mediated hypercalcemia of malignancy.