Twenty-one unselected patients with recurrent
nephrolithiasis and normocalcemic
hypercalciuria with or without
hypophosphatemia and 18 normal subjects were studied with an oral
calcium tolerance test and for 3- to 5-day periods while consuming a low normal (400 mg) and high-normal (1000 mg)
calcium intake. The oral
calcium tolerance test consisted of the measurement of the calcemic, calciuric, and parathyroid (assessed by determinations of serum immunoreactive
parathyroid hormone and nephrogenous cAMP) responses to acute 1000- or 350-mg doses of
calcium. Nineteen patients displayed normal results for basal serum
calcium, parathyroid function, and fasting
calcium excretion, and striking calcemic (mean increase in serum
calcium, 0.9 vs. 0.2 mg/dl in the normal subjects) and calciuric (mean increase in urinary
calcium, 0.33 vs. 0.15 mg
calcium/100 ml GF in the normal subjects) responses to the 1000-mg
calcium tolerance test, associated with a mean 54% suppression in nephrogenous cAMP. These patients were operationally defined as having "absorptive"
hypercalciuria. The variable occurrence of
hypophosphatemia in this group suggested that the pathogenesis of "absorptive"
hypercalciuria may be complex and/or multifactorial. There were strong positive correlations between the calciuric response to the
calcium tolerance test and fractional isotopic
calcium absorption (r = 0.75, P less than 0.00), the calcemic responses to the test (r = 0.71, P less than 0.001) and the calciuric responses noted on the 1000- vs. the 400-mg daily
calcium intake (r = 0.78, P less than 0.001). Two patients displayed low or low normal basal serum
calcium, increased parathyroid function, increased fasting
calcium excretion, and a striking calciuric but minimal calcemic response to the 1000-mg
calcium tolerance test, associated with a moderate suppression in nephrogenous cAMP. These patients were operationally defined as having "renal"
hypercalciuria. Several lines of evidence indicated that the
hyperparathyroidism in these patients was physiological or secondary, including the near normalization of parathyroid function on the daily 1000-mg
calcium intake. A steep slope of
calcium excretion on
calcium intake (due to increased
calcium absorption) was noted in all hypercalciuric patients and accounted for the significantly improved diagnostic accuracy of screening patients for
hypercalciuria on the high-normal
calcium intake. The simple measurement of total cAMP excretion (nanomoles per 100 ml GF) and urinary
calcium on the 1000-mg daily
calcium intake seemed to provide reliable separation of patients with "renal" from those with "absorptive"
hypercalciuria. A physiological (350 mg) dose of oral
calcium produced a 30% suppression of nephrogenous cAMP in normal subjects; this suggests that
dietary calcium exerts an important control of parathyroid function under physiological circumstances.