In a healthy 74-year-old woman with a comprehensive metabolic panel showing calcium 10.4 mg/dL, albumin 4.9 g/dL, and alkaline phosphatase 47 U/L, what is the most likely diagnosis and appropriate treatment?

Mild Hypercalcemia in a Healthy 74-Year-Old Woman

Most Likely Diagnosis

This patient has mild, asymptomatic hypercalcemia (corrected calcium 10.4 mg/dL) that most likely represents primary hyperparathyroidism (PHPT), which accounts for approximately 90% of hypercalcemia cases in this demographic. 1

The normal alkaline phosphatase (47 U/L) argues against high-turnover bone disease or malignancy-related bone metastases, while the elevated albumin (4.9 g/dL) suggests the corrected calcium may actually be lower than the measured value, making this truly mild hypercalcemia. 2, 3

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Immediate Diagnostic Workup

Essential First-Line Tests

• Measure intact parathyroid hormone (iPTH) immediately—this single test distinguishes PTH-dependent (PHPT) from PTH-independent causes and is the most important initial investigation. 3, 1

• Obtain a fasting ionized calcium level to confirm true hypercalcemia and avoid pseudo-hypercalcemia from hemoconcentration or recent calcium intake, which can cause transient elevations lasting several hours. 4

• Check serum phosphorus—low phosphorus supports PHPT, while normal or elevated phosphorus suggests malignancy or other causes. 3, 5

• Measure 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D together to exclude vitamin D intoxication or granulomatous disease (sarcoidosis, tuberculosis), where activated macrophages produce excess 1,25-(OH)₂ vitamin D. 3, 6

• Assess renal function (creatinine, BUN) because hypercalcemia can impair kidney function and CKD alters calcium metabolism. 3

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Interpretation Algorithm

If iPTH is Elevated or Inappropriately Normal (>20 pg/mL):

• Diagnosis: Primary hyperparathyroidism 1

• Proceed to parathyroid imaging (ultrasound ± sestamibi scan) if surgery is being considered. 1

• Rule out familial hypocalciuric hypercalcemia (FHH) by calculating 24-hour urinary calcium-to-creatinine clearance ratio; FHH shows avid renal calcium reabsorption (ratio <0.01) and does not require parathyroidectomy. 7

If iPTH is Suppressed (<20 pg/mL):

• Diagnosis: PTH-independent hypercalcemia 1, 5

• Check PTH-related protein (PTHrP)—elevated in most malignancy-associated hypercalcemia. 3

• If 1,25-(OH)₂ vitamin D is elevated with suppressed PTH, consider granulomatous disease (sarcoidosis, lymphoma) or vitamin D intoxication. 3, 6

• Obtain serum protein electrophoresis, immunofixation, and free light chains to exclude multiple myeloma. 3

• Consider CT chest/abdomen/pelvis and bone scan if malignancy is suspected. 3

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Treatment Approach

For Asymptomatic Mild Hypercalcemia (Calcium 10.4 mg/dL)

No acute intervention is required for mild, asymptomatic hypercalcemia. 1

If Primary Hyperparathyroidism is Confirmed:

• Parathyroidectomy is indicated if:

  • Age <50 years, OR
  • Serum calcium >1 mg/dL above upper normal limit (>11.0 mg/dL), OR
  • Evidence of skeletal disease (osteoporosis, fractures), OR
  • Evidence of kidney disease (nephrolithiasis, eGFR <60 mL/min, hypercalciuria >400 mg/24h). 1

• Observation with monitoring is appropriate if:

  • Age >50 years, AND
  • Calcium <1 mg/dL above upper limit (<11.0 mg/dL), AND
  • No skeletal or kidney involvement. 1

• Monitor serum calcium, creatinine, and bone density annually during observation. 1

If PTH-Independent Hypercalcemia:

• Discontinue all calcium supplements and vitamin D immediately—total elemental calcium intake should not exceed 2,000 mg/day. 3, 8

• For granulomatous disease or vitamin D intoxication: Start prednisone 20–40 mg/day orally to suppress 1α-hydroxylase activity and reduce intestinal calcium absorption. 3, 6

• For malignancy-associated hypercalcemia: Treat the underlying cancer when possible; median survival is approximately 1 month. 3

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Critical Pitfalls to Avoid

• Do not rely on corrected calcium formulas alone—they are inaccurate outside a limited range and can introduce errors. Always confirm with fasting ionized calcium for diagnostic purposes. 4

• Do not proceed to parathyroidectomy without ruling out FHH—FHH mimics PHPT but does not benefit from surgery and has no increased risk of complications. 7

• Do not assume hypercalcemia is benign without measuring iPTH—malignancy accounts for nearly half of all hypercalcemia cases and carries a poor prognosis. 1

• Ensure fasting samples—recent calcium intake or exercise can transiently elevate calcium levels, leading to unnecessary workup. 4

• Measure BOTH 25-OH vitamin D AND 1,25-(OH)₂ vitamin D together—checking only one can miss granulomatous disease or vitamin D intoxication. 3

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Summary Algorithm

1. Confirm hypercalcemia with fasting ionized calcium 4
2. Measure iPTH to distinguish PTH-dependent from PTH-independent causes 3, 1
3. If iPTH elevated/normal: Diagnose PHPT → assess surgical criteria → parathyroidectomy vs. observation 1
4. If iPTH suppressed: Check PTHrP, vitamin D metabolites, SPEP → treat underlying cause 3, 1
5. No acute treatment needed for mild, asymptomatic hypercalcemia 1