How should I manage a patient with severe hypercalcemia (serum calcium 14 mg/dL), an inappropriately normal parathyroid hormone (PTH 19.4 pg/mL), and non‑suppressed serum phosphorus (4.5 mg/dL)?

Severe Hypercalcemia with Inappropriately Normal PTH: Primary Hyperparathyroidism

This patient has severe hypercalcemia (14 mg/dL) with an inappropriately normal PTH (19.4 pg/mL) and non-suppressed phosphorus (4.5 mg/dL), which is diagnostic of primary hyperparathyroidism requiring urgent treatment followed by surgical evaluation. 1

Immediate Management: Severe Hypercalcemia Crisis

Your patient meets criteria for severe hypercalcemia (>14 mg/dL), which is a medical emergency associated with mental status changes, bradycardia, hypotension, severe dehydration, and acute renal failure. 1 This requires immediate intervention:

Acute Treatment Protocol

• Aggressive IV hydration with crystalloid fluids (not containing calcium) is the cornerstone of initial management, followed by loop diuretics after volume restoration. 1

• Intravenous bisphosphonates are first-line pharmacologic therapy for severe hypercalcemia. 1 Specifically, pamidronate 60-90 mg IV over 4 hours or zoledronic acid should be administered. 2, 3 The majority of patients (64%) show decreases in serum calcium by 24 hours after initiation, with 100% of patients receiving 90 mg pamidronate achieving normal calcium levels by day 7. 2

• Salmon calcitonin can be added for immediate short-term management of severe symptomatic hypercalcemia while awaiting bisphosphonate effect. 4, 5

• Discontinue any calcium supplements, vitamin D, or thiazide diuretics immediately. 1

Diagnostic Interpretation: Why This is Primary Hyperparathyroidism

The key diagnostic feature is that PTH is inappropriately normal (19.4 pg/mL) in the setting of severe hypercalcemia—it should be suppressed (<20 pg/mL) if the hypercalcemia were from another cause. 1, 3 This "inappropriately normal" PTH with hypercalcemia confirms primary hyperparathyroidism. 1

Critical Diagnostic Points

• The elevated or inappropriately normal PTH with hypercalcemia confirms primary hyperparathyroidism, as the parathyroid glands autonomously secrete PTH despite elevated calcium. 1

• The non-suppressed phosphorus (4.5 mg/dL) is atypical for primary hyperparathyroidism, which typically presents with low-normal phosphorus. 1 This finding, combined with severe hypercalcemia, raises concern for:

  • Atypical parathyroid adenoma versus parathyroid carcinoma 5
  • Coexisting conditions producing hypercalcemia 6
  • Impaired renal function affecting phosphorus handling 7

Essential Workup Before Surgery

Before proceeding to definitive treatment, complete the following diagnostic evaluation:

• Measure serum creatinine and eGFR to assess kidney function, as impaired kidney function (GFR <60 mL/min/1.73 m²) is both a complication of severe hypercalcemia and a surgical indication. 7, 1

• Check 25-hydroxyvitamin D levels to exclude vitamin D deficiency as a secondary cause of elevated PTH, though this is unlikely given the severe hypercalcemia. 7, 1

• Obtain 24-hour urine calcium or spot urine calcium/creatinine ratio to evaluate urinary calcium excretion and assess for hypercalciuria (>300 mg/24hr), which is a surgical indication. 1

• Order renal ultrasonography to assess for nephrocalcinosis or kidney stones. 1

Definitive Management: Surgical Referral

Parathyroidectomy is the only curative treatment and is absolutely indicated in this patient. 7 This patient meets multiple criteria for surgery:

Surgical Indications Met

• Corrected calcium >1 mg/dL above upper limit of normal (14 mg/dL is >3.7 mg/dL above the 10.3 mg/dL upper limit). 7, 1

• Severe symptomatic hypercalcemia requiring urgent intervention. 7

• Likely impaired kidney function given the severe hypercalcemia and elevated phosphorus. 7

Surgical Planning

• Refer immediately to both an endocrinologist and a high-volume parathyroid surgeon for coordinated management. 1

• Obtain preoperative localization imaging with sestamibi (99mTc-Sestamibi) scan with SPECT/CT and/or ultrasound once the diagnosis is biochemically confirmed, as sestamibi has the highest sensitivity for localizing parathyroid adenomas. 7, 1

• Minimally invasive parathyroidectomy (MIP) may be possible if imaging confidently localizes a single adenoma, offering shorter operating times and faster recovery. 7

Critical Pitfalls and Special Considerations

Beware of Atypical Features

The combination of severe hypercalcemia (14 mg/dL) with non-suppressed phosphorus (4.5 mg/dL) is concerning for atypical parathyroid adenoma or parathyroid carcinoma, which can be difficult to differentiate. 5 Parathyroid carcinoma should be suspected when:

• Serum calcium is markedly elevated (>14 mg/dL) 5
• PTH levels are very high (though yours is only mildly elevated) 8
• There is involvement of surrounding structures 5

Ensure the surgeon is aware of this possibility, as en bloc resection may be required rather than standard parathyroidectomy. 5

Rule Out Coexisting Malignancy

The occurrence of two conditions producing hypercalcemia is rare but should be considered with severe hypercalcemia and high-normal PTH. 6 If calcium remains elevated after bisphosphonate treatment despite rising PTH, this suggests coexisting malignancy-associated hypercalcemia. 6

Anticipate Hungry Bone Syndrome

After parathyroidectomy for severe hyperparathyroidism, patients frequently develop hungry bone syndrome with profound hypocalcemia requiring vigorous calcium, vitamin D, and calcitriol supplementation. 5 Plan for:

• Frequent calcium monitoring (every 6-12 hours initially) 7
• High-dose calcium supplementation (often 4-6 grams elemental calcium daily) 5
• Calcitriol 0.25-0.5 mcg twice daily 5

Monitor Closely During Acute Treatment

• Check serum calcium, phosphorus, and electrolytes every 2 weeks for 1 month after bisphosphonate initiation, then monthly. 7

• Reassess renal function regularly (creatinine, eGFR) as hypercalcemia can cause acute kidney injury and worsen chronic kidney disease. 1