A 28-year-old woman comes to the clinic for evaluation of an elevated calcium level discov… — USMLE Step 2 CK

A 28-year-old woman comes to the clinic for evaluation of an elevated calcium level discovered during a routine life insurance medical examination. The patient is completely asymptomatic and reports no fatigue, weakness, abdominal pain, constipation, or bone pain. She exercises regularly and takes no medications or over-the-counter supplements. Her family history is notable for her mother having "mildly elevated calcium" that persisted despite undergoing a parathyroidectomy several years ago. Vital signs and physical examination are unremarkable.

Laboratory studies show:
Serum calcium: $11.3\text{ mg/dL}$
Albumin: $4.0\text{ g/dL}$
Serum phosphorus: $2.6\text{ mg/dL}$
Creatinine: $0.8\text{ mg/dL}$
Intact parathyroid hormone: $62\text{ pg/mL}$ (normal: $10-65\text{ pg/mL}$ )

Which of the following is the most appropriate next step in the evaluation of this patient?

Measurement of urine calcium-to-creatinine clearance ratioAnswer
B
Technetium-99m sestamibi parathyroid scintigraphy
C
Measurement of parathyroid hormone-related peptide
D
Dual-energy x-ray absorptiometry scan
E
Administration of intravenous normal saline

Answer

Measurement of the urine calcium-to-creatinine clearance ratio is the next best step to differentiate familial hypocalciuric hypercalcemia from primary hyperparathyroidism.

The correct answer is measurement of the urine calcium-to-creatinine clearance ratio (UCCR). This patient has mild, asymptomatic hypercalcemia with an inappropriately normal intact parathyroid hormone (PTH) level. In a normal physiologic state, hypercalcemia completely suppresses PTH secretion. Therefore, a PTH level in the upper half of the normal reference range (

62\text{ pg/mL}

) in the setting of hypercalcemia indicates PTH-dependent hypercalcemia. The primary differential diagnosis for PTH-dependent hypercalcemia includes primary hyperparathyroidism and familial hypocalciuric hypercalcemia (FHH). This patient's family history of persistent hypercalcemia despite a parathyroidectomy strongly suggests FHH. FHH is an autosomal dominant disorder caused by an inactivating mutation in the calcium-sensing receptor (CaSR) located in the parathyroid glands and kidneys. This mutation leads to higher calcium levels being required to suppress PTH, as well as increased renal calcium reabsorption. The next best step to differentiate FHH from primary hyperparathyroidism is a urine collection to calculate the UCCR. A UCCR of less than 0.01 is highly suggestive of FHH, whereas a value greater than 0.02 points toward primary hyperparathyroidism. Recognizing FHH is crucial because it is a benign condition that does not require surgical intervention.

Step-by-Step Solution

Evaluate the relationship between the serum calcium and intact parathyroid hormone (PTH) levels.

The patient has hypercalcemia (

11.3\text{ mg/dL}

) with a concurrently high-normal PTH (

62\text{ pg/mL}

In the presence of hypercalcemia, a normal parathyroid gland should be strongly suppressed (PTH

< 20\text{ pg/mL}

). A value of

62\text{ pg/mL}

is inappropriately unsuppressed, indicating PTH-dependent hypercalcemia.

Formulate a differential diagnosis for PTH-dependent hypercalcemia based on the patient's history.

The primary differential includes primary hyperparathyroidism and familial hypocalciuric hypercalcemia (FHH).

The patient's family history of persistent hypercalcemia despite a parathyroidectomy strongly suggests FHH rather than primary hyperparathyroidism.

Identify the diagnostic test required to differentiate FHH from primary hyperparathyroidism.

Measurement of the 24-hour urine calcium-to-creatinine clearance ratio (UCCR).

FHH is characterized by increased renal calcium reabsorption resulting in a UCCR

< 0.01

, whereas primary hyperparathyroidism typically presents with a UCCR

> 0.02

Key Concept

The evaluation of PTH-dependent hypercalcemia and differentiating familial hypocalciuric hypercalcemia (FHH) from primary hyperparathyroidism.

Estimated Time:1m 30s

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