Effects of the Intravenous Administration of Calcium on Nephrogenous Cyclic AMP:Use as a Parathyroid Suppression Test*

Abstract

The question of parathyroid autonomy in primary hyperparathyroidism was the subject of conflicting immunoassay data. The effects of Ca infusion (12 mg/kg per 3 h) and Ca injection(3 mg/kg per 10 min) on peripheral plasma parthyroid hormone (i[immunoreactive]PTH) determined with a multivalent antiserum and on the excretion of nephrogenous cyclic[c]AMP were studied in normal subjects and in 7 patients with primary hyperparathyroidism who displayed only mild, intermittent hypercalcemia. In control subjects, Ca administration resulted in small (13-20%) reductions in iPTH, whereas some 4/5 (77-81%) of the nephrogenous cAMP was rapidly and uniformly suppressed. In the patients with primary hyperparathyroidism, both analyses revealed a lack of absolute parathyroid autonomy in response to Ca, with overlapping iPTH responses between a majority of the patients and the control group. In contrast, the nephrogenous cAMP responses provided a clear separation of the 2 groups after both Ca infusion and Ca injection (mean values for both studies, patients: 2.93 nmol/100 ml GF [glomerular filtration] vs. normal subjects; 0.38 nmol/100 ml GF), and measurements of total cAMP excretion also clearly distinguished the 2 groups. When a sensitive antiserum with predominantly carboxy-terminal reactivity was employed, the iPTH responses to Ca injection provided an improved separation of patients and normal subjects. Although parathyroid autonomy is not, in general, a feature of primary hyperparathyroidism, abnormal parathyroid suppressibility is easily demonstrated even in patients with a subtle form of the disorders. The determination of nephrogenous cAMP provides an optimal method for assessing rapid changes in parathyroid function. The interpretation of iPTH results from such studies is dependent on a number of technological features of the assay employed.