A -year-old man comes to the clinic for a routine health maintenance examination. He feels well and has no specific complaints. He has no history of nephrolithiasis, bone pain, fractures, or peptic ulcer disease. His family history is notable for asymptomatic hypercalcemia in his mother, which has never required treatment. He takes no medications. Vital signs are within normal limits. Physical examination reveals a healthy-appearing man with an unremarkable neck exam and normal deep tendon reflexes.
Laboratory results are as follows:
| Test | Result | Reference Range |
|---|---|---|
| Serum calcium | mg/dL | mg/dL |
| Serum albumin | g/dL | g/dL |
| Serum creatinine | mg/dL | mg/dL |
| Intact parathyroid hormone (PTH) | pg/mL | pg/mL |
Which of the following is the most appropriate next step in the evaluation of this patient's laboratory findings?
- Calculation of the urine calcium-to-creatinine clearance ratioAnswer
- BMeasurement of serum parathyroid hormone-related peptide
- CTechnetium-99m sestamibi parathyroid scintigraphy
- DMeasurement of serum 1,25-dihydroxyvitamin D
- EDual-energy x-ray absorptiometry scan
Answer
Calculation of the urine calcium-to-creatinine clearance ratio
This patient presents with asymptomatic hypercalcemia and an intact parathyroid hormone (PTH) level that is in the upper-normal range ( pg/mL). The initial step in evaluating hypercalcemia is determining if it is PTH-dependent or PTH-independent. In a normal physiologic state, hypercalcemia suppresses PTH secretion (typically to pg/mL). Therefore, an elevated OR "inappropriately normal" (mid-to-upper normal) PTH level in the setting of hypercalcemia indicates PTH-dependent hypercalcemia. The most common cause of PTH-dependent hypercalcemia is primary hyperparathyroidism (1° HPT), typically due to a single parathyroid adenoma. However, familial hypocalciuric hypercalcemia (FHH) is an important differential diagnosis that presents with identical initial biochemistry (mild hypercalcemia and inappropriately normal/elevated PTH). FHH is a benign, autosomal dominant disorder caused by a loss-of-function mutation in the calcium-sensing receptor (CaSR) in the parathyroid glands and kidneys. Because surgical parathyroidectomy is the treatment of choice for symptomatic 1° HPT but is ineffective and strictly contraindicated in FHH, the two must be differentiated. The next best step is calculating the urine calcium-to-creatinine clearance ratio (UCCR) using a 24-hour urine collection. A UCCR strongly suggests FHH, whereas a UCCR points toward 1° HPT.
Step-by-Step Solution
Key Concept
Patients with hypercalcemia and an inappropriately normal or elevated PTH level must have a urine calcium-to-creatinine clearance ratio calculated to differentiate primary hyperparathyroidism from familial hypocalciuric hypercalcemia.
Estimated Time:1m 0s