Is routine 24-hour urine calcium measurement useful during the evaluation of primary hyperparathyroidism?

Background: Primary hyperparathyroidism and familial hypocalciuric hypercalcemia have similar biochemical profiles, and calcium-to-creatinine-clearance ratio helps distinguish the two. Additionally, 24-hour urine calcium >400 mg/day indicates surgery and guidelines recommend obtaining 24-hour urine calcium preoperatively. Our aim was to assess how 24-hour urine calcium altered care in the evaluation of suspected primary hyperparathyroidism.

Methods: Consecutive patients assessed for primary hyperparathyroidism from 2018 to 2020 were reviewed. Primary hyperparathyroidism was diagnosed by 2016 American Association of Endocrine Surgeons Parathyroidectomy Guidelines criteria. 24-hour urine calcium-directed change in care was defined as familial hypocalciuric hypercalcemia diagnosis, surgical deferment for additional testing, or 24-hour urine calcium >400 mg/day as the sole surgical indication.

Results: Of 613 patients, 565 (92%) completed 24-hour urine calcium and 477 (84%) had concurrent biochemical testing to calculate calcium-to-creatinine-clearance ratio. 24-hour urine calcium was <100 mg/day in 9% (49/565) and calcium-to-creatinine-clearance ratio was <0.01 in 17% (82/477). No patient had confirmed familial hypocalciuric hypercalcemia, although 1 had a CASR variant of undetermined significance. When calcium-to-creatinine-clearance ratio was <0.01, familial hypocalciuric hypercalcemia was excluded by 24-hour urine calcium >100 mg/day (56%), prior normal calcium (16%), renal insufficiency (11%), absence of familial hypercalcemia (3%), normal repeat 24-hour urine calcium (10%), or interfering diuretic (1%). 24-hour urine calcium-directed change in care occurred in 25 (4%), including 4 (1%) who had genetic testing. Four-gland hyperplasia was more common with calcium-to-creatinine-clearance ratio <0.01 (17% vs calcium-to-creatinine-clearance ratio ≥ 0.01, 4%, P < .001), but surgical failure rates were equivalent (P = .24).

Conclusion: 24-hour urine calcium compliance was high, and results affected management in 4%, including productive identification of hypercalciuria as the sole surgical indication in 2 patients. When calcium-to-creatinine-clearance ratio <0.01, clinical assessment was sufficient to exclude familial hypocalciuric hypercalcemia and only 1% required genetic testing. 24-hour urine calcium should be ordered judiciously during primary hyperparathyroidism assessment.