PRIMARY HYPERPARATHYROIDISM WITH INTERMITTENT HYPERCALCAEMIA: SERIAL OBSERVATIONS AND SIMPLE DIAGNOSIS BY MEANS OF AN ORAL CALCIUM TOLERANCE TEST

Abstract

Ten patients with subtle primary hyperparathyroidism and intermittent hypercalcemia were followed serially for periods of 2-18 mo. (mean 10 mo.). Fasting serum Ca was elevated (> 10.6 mg/dl) in only 20% of determinations and fluctuated widely (9.1-11.2 mg/dl), yet the patients displayed a continuous, rather than episodic, basic disease process as defined by increases in nephrogenous cyclic[c]AMP and serum iPTH [immunoreactive parathyroid hormone]. Identical findings were noted in short-term (2-3 successive days) studies in 12 patients. In response to a 1000 mg oral Ca tolerance test, 12 patients with primary hyperparathyroidism and intermittent hypercalcemia (basal serum Ca 10.2 .+-. 0.2 mg/dl, mean .+-. SD) displayed: hyperabsorption of Ca (mean calciuric response twice normal); induced-hypercalcemia (mean serum Ca 11.4 mg/dl, with a mean increase of 1.2 mg/dl vs. 0.2 mg/dl in normal subjects) and abnormal parathyroid suppressibility (nephrogenous cAMP 2.66 .+-. 0.57 nmol/100 ml GF [glomerular filtrate] vs. 0.95 .+-. 0.40 nmol/100 ml GF in normal subjects, mean .+-. SD). The patients demonstrated striking hypercalciuria (452 .+-. 123 mg/24 h) on a 1000 mg metabolic Ca diet. Serum levels of 1,25(OH)2D3 [1,25-dihydroxy vitamin D3], measured in 10 patients, were markedly elevated at 90 .+-. 20 pg/ml (mean .+-. SD), and there was a strong positive correlation between the values for 1,25(OH)2D3 and the calciuric response to the Ca tolerance test (r [correlation coefficient] = 0.75, P < 0.001). The Ca tolerance test is apparently a simple and reliable technique for diagnosis of patients with primary hyperparathyroidism and intermittent hypercalcaemia; the important pathophysiologic features of this subtle clinical variant of primary hyperparathyroidism are also emphasized.