The Pathogenesis of Idiopathic Hypercalciuria: Evidence for Parathyroid Hyperfunction

We studied the effect of calcium deprivation and loading in17 healthy subjects and 76 patients with renal calculi. Fivehad primary hyperparathyroidism with an elevated plasma ionisedcalcium and detectable plasma parathyroid hormone. Forty-ninehad idiopathic hypercalciuria, defined by a urine calcium greaterthan 7 mmol/day on a free diet. Twenty-two were normo-calciuric.Fasting plasma calcium, corrected for albumin, was higher inthe patients with idiopathic hypercalciuria (2.40±0.10mmol/1) than in controls (2.28 ±0.05 mmol/1, p < 0.005).Plasma calcium was intermediate in the normocalciuric stoneformers (2.35 ±0.08 mmol/1) and elevated in the patientswith primary hyperparathyroidism (2.62 ± 0.07 mmol/1).Nephrogenous cyclic adenosine monophosphate (cAMP) and parathyroidhormone levels were highest in the primary hyperparathyroidgroup and did not differ significantly within the other groups.Nephrogenous cAMP correlated positively with plasma calciumin the patients with primary hyperparathyroidism and negativelyin controls; there was no correlation in the idio-pathic hypercalciuriagroup. Following an oral calcium load, plasma calcium rose andnephro-genous cAMP fell similarly in all groups. Fasting urinarycalcium and its increase after load were greatest in the idiopathichypercalciuria and primary hyperparathyroid groups, with inter-mediateresults in the normocalciuric patients. Neither the initialmetabolic patterns nor the response to thiazide fitted withthe previously described patterns of absorptive and renal hypercalciuria.Increased parathyroid gland activity is the most probable causeof idiopathic hypercalciuria.