What are the management steps for an adult patient with iron deficiency anemia and hypercalcemia, with a serum calcium level of 10.8 mg/dL?

Management of Hypercalcemia (10.8 mg/dL) with Iron Deficiency Anemia

A serum calcium of 10.8 mg/dL represents mild hypercalcemia that typically does not require acute intervention, but the concurrent iron deficiency anemia demands urgent investigation to exclude gastrointestinal malignancy, which could be the underlying cause of both conditions. 1

Initial Diagnostic Approach

Confirm Both Diagnoses

• Verify iron deficiency with serum ferritin (most specific test), transferrin saturation, and complete blood count showing microcytosis/hypochromia 2
• Measure intact parathyroid hormone (PTH) immediately—this is the single most important test to determine the cause of hypercalcemia 1, 3
  • Elevated or normal PTH = primary hyperparathyroidism (PHPT)
  • Suppressed PTH (<20 pg/mL) = malignancy or other non-PTH-mediated cause 1

Critical History Elements

• Duration of hypercalcemia: PHPT typically causes chronic hypercalcemia (>6 months) with calcium <12 mg/dL, while malignancy causes rapid onset with higher levels 3
• Gastrointestinal symptoms: weight loss, change in bowel habits, abdominal pain suggesting GI malignancy 2
• Constitutional symptoms: fatigue occurs in ~20% with mild hypercalcemia 1
• Medication review: thiazide diuretics, calcium/vitamin D supplements, lithium 1

Simultaneous Investigation Strategy

For Iron Deficiency Anemia

In men and postmenopausal women with newly diagnosed IDA, gastroscopy and colonoscopy should be performed urgently as first-line investigations 2, 4

• Perform urinalysis to exclude renal blood loss 2
• Screen for celiac disease serologically (found in 3-5% of IDA cases) 2
• Do NOT defer iron replacement while awaiting investigations unless colonoscopy is imminent 2
• Start one tablet daily of ferrous sulfate, fumarate, or gluconate; if not tolerated, give one tablet every other day or consider parenteral iron 2

For Hypercalcemia

• If PTH elevated/normal: Obtain sestamibi scan or ultrasound to localize parathyroid adenoma 1
• If PTH suppressed:
  • Check PTH-related protein (PTHrP) for humoral hypercalcemia of malignancy 5
  • Review imaging from endoscopy for occult malignancy 3
  • Consider chest imaging for lung cancer, check serum/urine protein electrophoresis for multiple myeloma 3

Management Algorithm

Mild Hypercalcemia (10.8 mg/dL) Management

No acute treatment needed at this calcium level 1

• Ensure adequate hydration (2-3 liters daily if no contraindications) 1, 3
• Avoid thiazide diuretics, calcium, and vitamin D supplements 1
• Monitor calcium weekly until diagnosis established 1

If Malignancy Confirmed

• Hypercalcemia of malignancy indicates poor prognosis and requires oncologic consultation 1
• If calcium rises to ≥12 mg/dL or becomes symptomatic:
  • IV hydration with normal saline 4, 5, 3
  • Zoledronic acid 4 mg IV over 15 minutes (preferred) or pamidronate 60-90 mg IV over 2-4 hours 4, 5, 1
  • For immediate effect while awaiting bisphosphonate action: calcitonin 4 IU/kg subcutaneously every 12 hours 3, 6

If Primary Hyperparathyroidism Confirmed

• Parathyroidectomy is definitive treatment and should be considered if: 1
  • Age <50 years, OR
  • Serum calcium >1 mg/dL above upper normal limit, OR
  • Evidence of kidney stones, reduced bone density, or renal dysfunction
• Observation acceptable if age >50 years, calcium <1 mg/dL above normal, and no end-organ damage 1

Critical Pitfall to Avoid

The coexistence of iron deficiency anemia and hypercalcemia strongly suggests gastrointestinal malignancy until proven otherwise. 2, 3 Primary hyperparathyroidism causes kidney stones and metabolic acidosis but never causes anemia, while malignancy-associated hypercalcemia typically presents with marked anemia 3. This patient requires urgent bidirectional endoscopy regardless of PTH results to exclude colorectal, gastric, or other GI malignancy 2, 4.

If Initial Endoscopy Negative

• Capsule endoscopy is the preferred test for small bowel evaluation if anemia persists or recurs after iron replacement 2, 1
• Renal tract imaging should be performed to exclude renal cell carcinoma (can cause both hypercalcemia and anemia) 2, 5

Monitoring

• Check hemoglobin response at 4 weeks after starting iron (expect ≥10 g/L rise if true iron deficiency) 2
• Continue iron for 3 months after hemoglobin normalizes to replenish stores 2
• Recheck serum calcium and creatinine before any bisphosphonate administration if treatment becomes necessary 4, 5