Renal Calculi

Most patients with normocalcemic hyperparathyroidism are identified because of renal calculi and many of these patients have hypercalciuria. Most patients with renal calculi and hypercalciuria, however, have idiopathic hypercalciuria, a condition also associated with normocalcemia. Patients with idiopathic hypercalciuria have 24-hour urinary calcium values of 250 mg per 24 hours or higher in females, 300 mg per 24 hours or higher in males, or 4 mg/kg in males or females on a daily intake of 1000 mg of calcium.28 These criteria are useful even when diet is uncontrolled because urine calcium excretion varies only slightly in normal

TOTAL CALCIUM (mg %)

12.0

11.0

normal range; is

IONIZED CALCIUM (mg %)

PATH.: Adenoma

FIGURE 45-2. Concurrent values of ionized and total calcium in a patient with renal calculi and intermittent elevation of the total calcium level. A parathyroid adenoma weighing 200 mg was removed at surgery. (From McLeod MK, Monchik JM, Martin HF. The role of ionized calcium in the diagnosis of subtle hypercalcemia in symptomatic primary hyperparathyroidism. Surgery 1984;95:667.)

CONSECUTIVE CONCURRENT VALUES (different days)

individuals when dietary calcium intake is widely altered.29 A small fraction of these patients with hypercalciuria have normocalcemic HPTH.30 Figure 45-2 shows concomitant ionized and total calcium values in a patient with nephrolithiasis and intermittent elevation of the total calcium, and Figure 45-3 demonstrates a patient with renal calculi with no elevation of the total calcium.

Since the original description of idiopathic hypercalciuria by Albright and associates in 1953, several hypothesis have been advanced to explain this entity.31 Increased intestinal absorption, diminished tubular resorption of calcium resulting in a renal calcium leak, and a primary phosphate leak have been postulated.32 34 In practice, the classification of idiopathic hypercalciuria stone formers into renal calcium leak, primary intestinal hyperabsorption, or primary phosphate leak is time consuming, expensive, not reproducible, and does not appear to influence the outcome of treatment.

The differentiation of hypercalciuric stone formers with normocalcemic hyperparathyroidism from those with one of the subtypes of idiopathic hypercalciuria is of prime importance because of the success of parathyroid surgery in preventing further stone formation. Failure to accurately separate stone-forming patients with normocalcemic hyperparathyroidism from those with idiopathic hypercalciuria has led to inappropriate neck exploration. Parathyroid surgery in patients with idiopathic hypercalciuria has resulted in finding no abnormal parathyroid tissue and continued stone formation.35

The renal calcium leak subtype of idiopathic hypercalciuria can have an elevated serum PTH secondary to compensation by the parathyroid glands to increased renal loss of calcium. The serum ionized or total calcium is not elevated in this or other subtypes of idiopathic hypercalciuria.36 The absence of an elevated serum ionized or total calcium makes further testing necessary to distinguish this entity from normocalcemic hyperparathyroidism. This subtype of idiopathic hypercalciuria can sometimes be separated from normocalcemic hyperparathyroidism by treatment with a thiazide diuretic. The thiazide diuretic reduces the excessive loss of urinary calcium, causing the serum calcium to rise slightly but not above, the normal range, and resulting in a decrease of the serum PTH into the normal range.37,38

FIGURE 45-3. Concurrent values of ionized and total calcium levels in a patient with renal calculi and all normal total calcium levels. A parathyroid adenoma weighing 440 mg was removed at surgery. (From McLeod MK, Monchik JM, Martin HF. The role of ionized calcium in the diagnosis of subtle hypercalcemia in symptomatic primary hyperparathyroidism. Surgery 1984;95:667.)

TOTAL CALCIUM (mg %)

IONIZED CALCIUM (mg %) PATH.: Adenoma

TOTAL CALCIUM (mg %)

12.0

11.0

IONIZED CALCIUM (mg %) PATH.: Adenoma

% NORMAL RANSE

1 23456789 10 CONSECUTIVE CONCURRENT VALUES (different days)

I have shown that ionized calcium is more sensitive than total calcium in diagnosing PHPT in patients with nephrolithiasis and minimal or no elevation of the total calcium.723 We recommend three consecutive days of ionized and total calcium as a screening study for hyperparathyroidism in patients with nephrolithiasis with minimal or no elevation of the serum total calcium. A serum iPTH should be done on at least one day. An elevated iPTH may be the only clue to the diagnosis of normocalcemic hyperparathyroidism.26

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Dieting Dilemma and Skinny Solutions

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