In a 73-year-old man with ionized calcium 5.9 mg/dL and intact PTH 100 pg/mL, what is the most likely diagnosis and how should the hypercalcemia be managed?

Primary Hyperparathyroidism with Severe Hypercalcemia

This 73-year-old man has primary hyperparathyroidism (PHPT) causing severe hypercalcemia that requires immediate aggressive medical management followed by urgent surgical referral for parathyroidectomy.

Diagnostic Interpretation

The laboratory values confirm primary hyperparathyroidism:

• Ionized calcium of 5.9 mg/dL (1.48 mmol/L) represents severe hypercalcemia, well above the normal range of 4.6-5.4 mg/dL (1.15-1.36 mmol/L) 1, 2
• PTH of 100 pg/mL is inappropriately elevated in the setting of hypercalcemia, when it should be suppressed below 20 pg/mL 2, 3
• This combination—elevated calcium with elevated or inappropriately normal PTH—is diagnostic of primary hyperparathyroidism 4, 2

The ionized calcium measurement is particularly valuable here because it directly measures the biologically active fraction and is more sensitive than total calcium for detecting PHPT 5.

Immediate Medical Management

Initiate aggressive intravenous hydration with normal saline to restore intravascular volume and promote calciuresis, as this is the cornerstone of acute hypercalcemia management 1, 4, 2. The goal is to correct the volume depletion that invariably accompanies severe hypercalcemia.

Administer intravenous bisphosphonates—specifically zoledronic acid or pamidronate—as first-line pharmacologic therapy 1, 4, 2. These agents inhibit osteoclast-mediated bone resorption and typically lower calcium within 2-4 days.

Add loop diuretics (furosemide) only after adequate volume repletion to enhance urinary calcium excretion 4. Administering diuretics before volume restoration will worsen dehydration and renal function.

Consider calcitonin as a temporizing measure if rapid calcium reduction is needed while awaiting bisphosphonate effect, though its efficacy is limited and tachyphylaxis develops quickly 4, 2.

Monitoring During Acute Treatment

• Measure ionized calcium every 4-6 hours initially to track response to therapy 1, 4
• Monitor serum creatinine and electrolytes closely, as severe hypercalcemia can cause acute kidney injury 4
• Assess mental status, as severe hypercalcemia (ionized calcium >10 mg/dL or total calcium ≥14 mg/dL) can cause confusion, somnolence, and altered consciousness 2

Definitive Surgical Management

Refer urgently to an experienced, high-volume parathyroid surgeon for parathyroidectomy, as this patient meets multiple surgical indications 6, 4:

• Age >50 years with symptomatic hypercalcemia
• Corrected calcium >1 mg/dL above upper limit of normal
• Parathyroidectomy is the only definitive curative therapy for PHPT 6

Obtain preoperative localization imaging with sestamibi scan and/or ultrasound once the diagnosis is biochemically confirmed and surgery is planned 6, 4. This facilitates minimally invasive parathyroidectomy rather than bilateral neck exploration.

Essential Pre-Surgical Workup

Before surgical referral, complete the following:

• Measure 25-hydroxyvitamin D to exclude vitamin D deficiency as a contributor to secondary hyperparathyroidism 4
• Assess renal function with serum creatinine and eGFR, as impaired kidney function (eGFR <60 mL/min/1.73 m²) is itself a surgical indication 4
• Obtain 24-hour urine calcium or spot urine calcium/creatinine ratio to evaluate for hypercalciuria 4
• Order bone density scan (DEXA) to assess for osteoporosis, which is another surgical indication 4

Post-Operative Management Considerations

After parathyroidectomy, this patient is at high risk for "hungry bone syndrome"—rapid, severe hypocalcemia due to sudden remineralization of chronically depleted bone 4:

• Monitor ionized calcium every 4-6 hours for the first 48-72 hours post-operatively 1, 4
• 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 1, 4
• Transition to oral calcium carbonate 1-2 g three times daily plus calcitriol up to 2 μg/day once oral intake is tolerated 1, 4

Critical Pitfalls to Avoid

Do not delay surgery for prolonged medical management in a symptomatic patient with clear biochemical diagnosis 6. Medical therapy is temporizing only.

Do not order parathyroid imaging before confirming the biochemical diagnosis, as imaging is for surgical planning, not diagnosis 4.

Do not supplement with vitamin D or calcium during the acute hypercalcemic phase, as this will worsen hypercalcemia 4, 7.

Do not use calcium-based phosphate binders if the patient has chronic kidney disease, as these will exacerbate hypercalcemia 4, 7.

Prognosis

The prognosis for surgically treated PHPT is excellent, with cure rates exceeding 95% in experienced hands 2. However, untreated severe hypercalcemia carries significant morbidity including nephrolithiasis, bone disease, cardiovascular complications, and neuropsychiatric symptoms 8, 2.