What investigations are needed for a patient with hypercalcemia?

Investigations for Severe Hypercalcemia (15.5 mg/dL)

For a patient with severe hypercalcemia of 15.5 mg/dL, a comprehensive diagnostic workup should include measurement of intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), vitamin D levels, and other essential laboratory tests to determine the underlying cause, as this level represents a medical emergency requiring urgent intervention. 1

Initial Laboratory Investigations

• Confirm hypercalcemia: Calculate albumin-corrected calcium using the formula: Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1

• Essential laboratory tests:

  • Intact parathyroid hormone (iPTH)
  • Parathyroid hormone-related protein (PTHrP)
  • 25-hydroxyvitamin D
  • 1,25-dihydroxyvitamin D
  • Complete blood count
  • Serum phosphorus
  • Serum magnesium
  • Serum creatinine and BUN
  • Urinalysis and 24-hour urinary calcium
  • Thyroid-stimulating hormone (TSH)
  • Liver function tests 1

Diagnostic Algorithm Based on PTH Results

If PTH is elevated or inappropriately normal:

• Primary hyperparathyroidism is likely
• Additional tests:
  • Neck ultrasound
  • Sestamibi scan of the parathyroid glands
  • Neck CT or MRI if localization is difficult 1

If PTH is suppressed (<20 pg/mL):

• Malignancy-related hypercalcemia is most likely
• Additional tests:
  • Chest X-ray or CT
  • Mammography (in women)
  • Prostate-specific antigen (in men)
  • Serum and urine protein electrophoresis (to rule out multiple myeloma)
  • Bone scan
  • CT scan of chest, abdomen, and pelvis 1

Specific Investigations Based on Clinical Suspicion

• For suspected malignancy:

  • Evaluation for bone metastases
  • Multiple myeloma workup (serum and urine protein electrophoresis)
  • Humoral hypercalcemia of malignancy markers 1

• For suspected granulomatous diseases:

  • Chest X-ray or CT (for sarcoidosis)
  • Angiotensin-converting enzyme levels
  • Tuberculin skin test or interferon-gamma release assay 1

• For medication-induced hypercalcemia:

  • Review of all medications, especially thiazide diuretics, lithium, and vitamin A or D supplements 2

• For familial hypocalciuric hypercalcemia:

  • 24-hour urinary calcium excretion
  • Calcium/creatinine clearance ratio 3

Urgent Management While Investigating

Given the severity of hypercalcemia (15.5 mg/dL), urgent treatment should be initiated concurrently with diagnostic workup:

1. Aggressive IV fluid resuscitation with normal saline to correct hypovolemia and promote calciuresis 1, 4

2. Bisphosphonates (e.g., zoledronic acid 4 mg IV over 15 minutes) as first-line pharmacological intervention 1

3. Monitor serum calcium, phosphate, magnesium, renal function, and electrolytes regularly 1

Common Pitfalls to Avoid

• Delaying treatment of severe hypercalcemia while waiting for diagnostic results
• Using diuretics before correcting hypovolemia
• Failing to correct calcium for albumin
• Inadequate hydration before bisphosphonate administration
• Treating laboratory values without addressing the underlying cause 1

A calcium level of 15.5 mg/dL represents severe hypercalcemia that can lead to significant morbidity and mortality if not promptly diagnosed and treated. The diagnostic approach should be systematic while simultaneously initiating treatment to lower calcium levels.