In a 71-year-old man with mild persistent hypercalcemia, normal intact parathyroid hormone, normal 1,25‑hydroxyvitamin D, normal PTH‑related protein, elevated urinary calcium excretion, remote nephrolithiasis, and mild osteopenia, is parathyroidectomy indicated?

Does This Patient Need Parathyroidectomy?

No, this patient does not have primary hyperparathyroidism and does not need parathyroidectomy. The normal intact PTH in the setting of hypercalcemia excludes primary hyperparathyroidism and indicates a PTH-independent cause of hypercalcemia that requires further investigation before any surgical intervention is considered.

Why This Is Not Primary Hyperparathyroidism

Primary hyperparathyroidism is definitively excluded by the laboratory findings. The diagnosis requires elevated or inappropriately normal PTH (typically >65 pg/mL depending on assay) in the presence of hypercalcemia 1. When PTH is truly normal (mid-range of reference interval) with hypercalcemia, this represents PTH-independent hypercalcemia, not primary hyperparathyroidism 2, 3.

• In primary hyperparathyroidism, the parathyroid glands autonomously secrete PTH despite elevated calcium, resulting in elevated or "inappropriately normal" PTH levels (meaning PTH fails to suppress below 20 pg/mL as it should with hypercalcemia) 1.
• A suppressed PTH (<20 pg/mL) indicates PTH-independent hypercalcemia from causes such as malignancy, granulomatous disease, vitamin D intoxication, or medication effects 2, 3.
• The distinction is critical: parathyroidectomy is only indicated for confirmed primary hyperparathyroidism with elevated or inappropriately elevated PTH 4, 5.

Critical Diagnostic Steps Required Immediately

Measure PTH-related protein (PTHrP), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D simultaneously before any treatment decisions. These tests distinguish the major causes of PTH-independent hypercalcemia 1, 2.

Essential Laboratory Panel

• PTHrP measurement: Elevated PTHrP with suppressed PTH defines humoral hypercalcemia of malignancy, which carries a median survival of approximately 1 month and requires urgent malignancy work-up with chest/abdominal/pelvic CT and PET-CT 1.
• 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D together: The relationship between these two provides critical diagnostic information 1.
  • Markedly elevated 25-OH vitamin D indicates vitamin D intoxication 1.
  • Low 25-OH vitamin D but elevated 1,25-(OH)₂ vitamin D suggests granulomatous disease (sarcoidosis) due to increased 1α-hydroxylase activity in granulomas 1.
• Medication review: Discontinue thiazide diuretics, calcium supplements, vitamin D supplements, and review for lithium, which can all cause hypercalcemia 2, 1.

The Elevated Urinary Calcium Is a Red Herring

Elevated urinary calcium (430 mg/24hr) with hypercalcemia is expected regardless of the underlying cause. Hypercalcemia increases the filtered load of calcium, resulting in hypercalciuria 6. This finding does not distinguish between causes of hypercalcemia and does not support the diagnosis of primary hyperparathyroidism when PTH is normal 6.

• In primary hyperparathyroidism, urinary calcium typically exceeds absorbed calcium from the intestinal tract due to excessive skeletal resorption (resorptive hypercalciuria), but this occurs in the setting of elevated PTH 6.
• The remote history of kidney stones could reflect prior episodes of hypercalciuria from any cause, not necessarily hyperparathyroidism 6.

What About Normocalcemic Primary Hyperparathyroidism?

This patient has hypercalcemia (10.8-11 mg/dL, ionized calcium 5.6 mg/dL), not normocalcemia, so normocalcemic primary hyperparathyroidism is not applicable. Normocalcemic primary hyperparathyroidism requires persistently elevated PTH with consistently normal albumin-corrected serum calcium after exclusion of all secondary causes 1.

• The ionized calcium of 5.6 mg/dL exceeds the normal range of 4.6-5.4 mg/dL (1.15-1.36 mmol/L), confirming true hypercalcemia 1, 2.
• Even in normocalcemic primary hyperparathyroidism, PTH must be elevated, not normal 1.

Immediate Management Priorities

Ensure adequate oral hydration and discontinue any calcium supplements, vitamin D, or thiazide diuretics immediately. This is the cornerstone of managing mild hypercalcemia (10.2-12 mg/dL) 1.

Monitoring Strategy

• Measure serum calcium every 3 months until the underlying cause is identified and treated 1.
• Reassess renal function regularly (creatinine, eGFR) as hypercalcemia can cause acute kidney injury and worsen chronic kidney disease 1.
• Obtain renal ultrasonography to assess for nephrocalcinosis or kidney stones 1.

When to Escalate Treatment

• If calcium rises above 12 mg/dL or symptoms develop (nausea, vomiting, confusion), initiate aggressive IV hydration with isotonic normal saline and consider IV bisphosphonates (zoledronic acid or pamidronate) 1, 2, 3.
• Glucocorticoids are effective for vitamin D-mediated hypercalcemia (vitamin D intoxication, sarcoidosis, lymphomas) once the diagnosis is confirmed 1, 2.

Common Pitfalls to Avoid

Do not order parathyroid imaging (sestamibi scan, ultrasound) before confirming the biochemical diagnosis of primary hyperparathyroidism. Imaging is for surgical planning after diagnosis is established, not for diagnosis itself 1.

• Parathyroid adenomas can be incidental findings in up to 2-3% of the general population and do not cause hypercalcemia unless PTH is elevated 5.
• Proceeding to parathyroidectomy without elevated PTH will not cure the hypercalcemia and exposes the patient to unnecessary surgical risk 5.

Do not assume "normal" PTH in the setting of hypercalcemia is the same as "inappropriately normal" PTH. The distinction depends on the absolute PTH value and assay-specific reference ranges 1.

• PTH should be suppressed below 20 pg/mL when calcium is elevated; failure to suppress indicates primary hyperparathyroidism 2, 3.
• If the reported "normal" PTH is in the mid-to-upper range of normal (e.g., 40-65 pg/mL), this may represent inappropriately normal PTH and warrant endocrinology referral 1.
• PTH assays vary by up to 47% between different generations, so use assay-specific reference values 1.

Next Steps: Algorithmic Approach

1. Immediately: Stop all calcium, vitamin D supplements, and thiazide diuretics 1.
2. Order stat: PTHrP, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D 1, 2.
3. If PTHrP elevated: Urgent malignancy work-up with CT chest/abdomen/pelvis and PET-CT; median survival is 1 month 1.
4. If 25-OH vitamin D markedly elevated: Diagnose vitamin D intoxication; treat with hydration and glucocorticoids if severe 1, 2.
5. If 25-OH vitamin D low but 1,25-(OH)₂ vitamin D elevated: Evaluate for sarcoidosis or other granulomatous disease with chest CT, ACE level, and consider tissue biopsy 1.
6. If all tests normal: Consider medication-induced hypercalcemia, immobilization, or rare causes; refer to endocrinology 2.
7. Only if PTH is confirmed elevated (>65 pg/mL) on repeat testing: Diagnose primary hyperparathyroidism and refer to endocrinology and experienced parathyroid surgeon for surgical evaluation 1, 5.