What is the next step for a patient with recurrent calcium phosphate stones and hypercalcemia?

Management of Recurrent Calcium Phosphate Stone Former with Hypercalcemia

The next step for a patient with recurrent calcium phosphate stones and hypercalcemia (serum calcium of 11 mg/dL) should be measurement of serum intact parathyroid hormone (PTH) to evaluate for primary hyperparathyroidism. 1

Diagnostic Approach

• Elevated serum calcium (hypercalcemia) in a recurrent calcium phosphate stone former strongly suggests primary hyperparathyroidism (PHPT), which accounts for approximately 90% of hypercalcemia cases 1
• Serum intact parathyroid hormone (PTH) is the most important initial test to evaluate hypercalcemia, as it distinguishes PTH-dependent from PTH-independent causes 1
• In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (<20 pg/mL depending on assay) indicates another cause 1
• Complete metabolic evaluation should include one or two 24-hour urine collections analyzed for total volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine 2

Treatment Algorithm Based on PTH Results

If PTH is elevated or inappropriately normal (suggesting PHPT):

1. Surgical Management:

   • Parathyroidectomy is the definitive treatment for PHPT 1
   • Surgery should be considered depending on age, serum calcium level, and kidney or skeletal involvement 1

2. Medical Management (if surgery is delayed or contraindicated):

   • Increase fluid intake to achieve urine volume of at least 2.5 liters daily 2
   • Limit sodium intake to 2,300 mg (100 mEq) daily to reduce urinary calcium excretion 2
   • Maintain normal dietary calcium intake of 1,000-1,200 mg per day 2
   • Potassium citrate therapy should be offered to calcium phosphate stone formers with hypocitraturia 3
   • Avoid thiazide diuretics in patients with confirmed PHPT as they may worsen hypercalcemia 4

If PTH is suppressed (suggesting non-PTH mediated hypercalcemia):

1. Further Evaluation:

   • Consider other causes of hypercalcemia such as malignancy, granulomatous disease, vitamin D intoxication, or medications 1
   • Check for hypercalcemia-inducing medications like thiazides 1

2. Initial Management:

   • Hydration and intravenous bisphosphonates for symptomatic or severe hypercalcemia 1
   • Glucocorticoids may be used when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders) 1

Stone-Specific Management

• Potassium citrate therapy should be offered to patients with recurrent calcium stones and low or relatively low urinary citrate 3, 5
• Potassium citrate is particularly important for calcium phosphate stone formers with hypocitraturia because citrate is a known potent inhibitor of calcium phosphate crystallization 3
• Potassium citrate is preferred over sodium citrate, as the sodium load in the latter may increase urine calcium excretion 3, 2
• Increased fluid intake, sodium restriction, and ample fruits and vegetables may increase the safety and efficacy of citrate therapy 3, 2

Monitoring and Follow-up

• Obtain a 24-hour urine specimen within six months of initiating treatment to assess response to therapy 5
• Annual 24-hour urine collections are recommended for ongoing monitoring, with more frequent testing depending on stone activity 5
• Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at appropriate intervals 4

Common Pitfalls and Caveats

• Inadequate fluid intake remains a major risk factor for stone recurrence regardless of pharmacological intervention 5
• Dietary calcium restriction should be avoided as it can paradoxically increase stone risk 2
• Calcium supplements should be avoided, as they may increase stone risk unlike dietary calcium 2
• Marked hypercalcemia may be evidence of hidden hyperparathyroidism, and thiazides should be discontinued before carrying out tests for parathyroid function 4
• In patients with PHPT, thiazide diuretics should be avoided as they may worsen hypercalcemia 4