What is the management approach for a patient with hypercalcemia, elevated Parathyroid Hormone (PTH) levels, and mild anemia with normal iron and B12 levels?

Management of Hypercalcemia with Elevated PTH and Mild Anemia

This patient has primary hyperparathyroidism (PHPT) and requires parathyroidectomy if they meet surgical criteria, which should be assessed immediately. 1, 2

Diagnostic Confirmation and Initial Workup

The combination of hypercalcemia with elevated PTH confirms primary hyperparathyroidism, as PTH should be suppressed in non-PTH-dependent causes of hypercalcemia. 3 The mild normocytic anemia (Hgb 12.9, MCV 99) with normal iron and B12 is likely unrelated to the hyperparathyroidism itself but warrants consideration of chronic disease or other causes. 3

Essential immediate laboratory tests include:

• Measure 25-OH vitamin D levels to exclude vitamin D deficiency as a concomitant secondary cause, targeting levels >20 ng/mL (50 nmol/L). 1, 2
• Calculate eGFR from serum creatinine, as eGFR <60 mL/min/1.73 m² is an absolute surgical indication. 2
• Obtain 24-hour urine calcium to assess for marked hypercalciuria (>400 mg/24h), which indicates increased risk of nephrolithiasis and represents a surgical indication. 4
• Measure serum phosphate, which is typically low or low-normal in PHPT. 2

Surgical Indications Assessment

Parathyroidectomy is indicated if the patient meets any of the following criteria: 1, 2

• Age <50 years
• Serum calcium >0.25 mmol/L (>1 mg/dL) above upper limit of normal
• eGFR <60 mL/min/1.73 m²
• Presence of nephrolithiasis or nephrocalcinosis
• 24-hour urine calcium >400 mg/24h
• Evidence of osteoporosis on bone densitometry
• PTH >800 pg/mL with refractory hypercalcemia (severe disease)

If surgical criteria are met, proceed with preoperative localization imaging using ultrasound and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT. 1 Minimally invasive parathyroidectomy (MIP) offers shorter operating times and faster recovery compared to bilateral neck exploration. 1

Medical Management if Surgery is Deferred

If the patient does not meet surgical criteria (age >50 years, calcium <1 mg/dL above upper limit, normal renal function, no stones, no osteoporosis), medical management is appropriate: 5, 6

Optimize calcium and vitamin D status:

• Ensure adequate dietary calcium intake (not excessive, not restricted) through dietary evaluation. 1
• Supplement vitamin D to achieve 25-OH vitamin D levels >20 ng/mL, as vitamin D deficiency can worsen PTH elevation. 1, 2
• Avoid calcium supplementation if serum calcium is already elevated, as this may worsen hypercalcemia. 4

For skeletal protection if osteoporosis is present:

• Consider antiresorptive therapy (bisphosphonates or denosumab) for fracture risk reduction, though evidence for fracture reduction in PHPT specifically is limited. 5

For persistent hypercalcemia:

• Cinacalcet (calcimimetic) can effectively lower serum calcium and PTH levels in patients who cannot undergo surgery, starting at 30 mg twice daily and titrating up to 90 mg four times daily as needed. 7, 5
• In the FDA trial, 75.8% of PHPT patients achieved normal calcium levels with cinacalcet versus 0% with placebo. 7

Addressing the Anemia

The mild normocytic anemia requires separate evaluation: 3

• Check reticulocyte count, peripheral smear, and consider additional workup for anemia of chronic disease, occult blood loss, or other causes unrelated to hyperparathyroidism.
• Renal function assessment is critical, as even mild CKD can contribute to anemia and would change the surgical indication status. 2

Post-Surgical Management (If Surgery Performed)

Monitor ionized calcium every 4-6 hours for the first 48-72 hours after parathyroidectomy, then twice daily until stable. 8, 1

If ionized calcium falls below 0.9 mmol/L (3.6 mg/dL):

• Initiate calcium gluconate infusion at 1-2 mg elemental calcium/kg/hour, adjusting to maintain ionized calcium 1.15-1.36 mmol/L (4.6-5.4 mg/dL). 8
• Provide oral calcium carbonate and calcitriol when oral intake is possible. 1

Critical Pitfalls to Avoid

• Do not delay surgical evaluation in patients meeting criteria, as progressive renal damage and bone loss can occur. 4
• Do not use thiazide diuretics in PHPT patients, as they reduce urinary calcium excretion and worsen hypercalcemia. 4
• Do not assume the anemia is related to hyperparathyroidism without proper workup, as it may represent a separate significant pathology. 3
• Do not interpret PTH levels without checking vitamin D status, as vitamin D deficiency can elevate PTH and complicate diagnosis. 2