During a routine employment health screening, a -year-old female healthcare worker is found to have an incidental laboratory abnormality. She reports feeling completely well and denies a history of nephrolithiasis, bone pain, abdominal discomfort, or changes in mood. She takes no prescription or over-the-counter medications. Her family history is notable for a father who was told he had "mildly high calcium" but never required medical or surgical intervention.
Vital signs are within normal limits. Physical examination is unremarkable.
Initial and follow-up laboratory testing reveal the following:
| Laboratory Test | Result | Reference Range |
|---|---|---|
| Serum calcium | mg/dL | mg/dL |
| Serum albumin | g/dL | g/dL |
| Serum phosphorus | mg/dL | mg/dL |
| Intact PTH | pg/mL | pg/mL |
| 25-hydroxyvitamin D | ng/mL | ng/mL |
| Serum creatinine | mg/dL | mg/dL |
| 24-hour urine calcium | mg/24 hr | mg/24 hr |
| 24-hour urine creatinine | mg/24 hr | mg/24 hr |
Based on the provided laboratory results, which of the following is the most likely diagnosis?
- Familial hypocalciuric hypercalcemiaAnswer
- BPrimary hyperparathyroidism
- CSurreptitious thiazide diuretic use
- DHumoral hypercalcemia of malignancy
- EGranulomatous disease
Answer
Familial hypocalciuric hypercalcemia
The correct diagnosis is familial hypocalciuric hypercalcemia (FHH). The interpretation of this laboratory panel begins with confirming hypercalcemia ( mg/dL) alongside an intact PTH level ( pg/mL) that is inappropriately normal (unsuppressed). In a normal physiologic state, hypercalcemia should profoundly suppress parathyroid hormone secretion. An unsuppressed PTH narrows the differential to PTH-dependent causes, primarily primary hyperparathyroidism and FHH. The critical differentiating test is the 24-hour urine calcium. In primary hyperparathyroidism, the kidneys are structurally normal and will attempt to excrete the excessive filtered calcium load, resulting in normal or elevated 24-hour urine calcium ( mg/day). In contrast, FHH is caused by an inactivating mutation in the calcium-sensing receptor (CaSR) in both the parathyroid glands and the renal tubules. The renal mutation leads to increased tubular calcium reabsorption, resulting in significant hypocalciuria ( mg/day). The patient's asymptomatic status and family history of benign hypercalcemia further secure this diagnosis.
Step-by-Step Solution
Key Concept
The hallmark laboratory pattern of familial hypocalciuric hypercalcemia (FHH) is mild hypercalcemia, inappropriately normal or slightly elevated PTH, and a very low 24-hour urine calcium level.