What is the likely diagnosis and recommended workup for a patient with serum calcium of 10.5 mg/dL and intact parathyroid hormone (PTH) of 120 pg/mL?

Primary Hyperparathyroidism (PHPT)

This patient has primary hyperparathyroidism (PHPT), confirmed by the combination of elevated calcium (10.5 mg/dL, which is above the typical upper limit of 10.2-10.4 mg/dL) and inappropriately elevated PTH (120 pg/mL). 1

Diagnostic Confirmation

The biochemical profile is diagnostic for PHPT:

• Hypercalcemia with elevated PTH is pathognomonic - any PTH level that is not suppressed (i.e., measurable or elevated) in the setting of hypercalcemia indicates autonomous parathyroid function 1
• The PTH of 120 pg/mL is frankly elevated (normal range typically 10-65 pg/mL), making this a classic presentation rather than an atypical form 2
• In the largest surgical series of 10,000 PHPT patients, the average PTH was 105.8 ± 48 pg/mL, placing this patient squarely within the typical range 2

Essential Workup - Target Organ Assessment

You must systematically evaluate for end-organ damage, as this determines surgical candidacy and urgency: 1

Renal Assessment (Grade A++)

• 24-hour urine calcium - hypercalciuria >250 mg/day (women) or >300 mg/day (men) is a surgical indication 1
• Fractional excretion of calcium (FeCa) - calculate using: (UCa × PCr)/(UCr × PCa) × 100. FeCa >2% confirms PHPT and excludes familial hypocalciuric hypercalcemia 1, 3
• eGFR/creatinine - GFR <60 mL/min/1.73m² is an absolute surgical indication 1
• Renal imaging - non-contrast CT scan (preferred over ultrasound for sensitivity) to detect nephrolithiasis or nephrocalcinosis 1

Bone Assessment (Grade A++)

• DEXA scan - measure spine, hip, AND distal 1/3 radius. T-score ≤-2.5 at any site mandates surgery 1
• Spine imaging - X-ray or vertebral fracture assessment to detect asymptomatic vertebral fractures, which are surgical indications 1

Critical Pre-Diagnosis Steps

Before finalizing the PHPT diagnosis, you must exclude secondary causes:

• 25-OH vitamin D level - vitamin D deficiency can cause secondary hyperparathyroidism. The patient needs vitamin D >30 ng/mL (75 nmol/L) maintained for >6 months before accepting a diagnosis of normocalcemic PHPT (though this patient is hypercalcemic, making this less critical) 1, 3
• Assess calcium intake - inadequate dietary calcium can trigger secondary hyperparathyroidism 3

Surgical Indications

Surgery should be offered if ANY of the following criteria are met: 1

• Calcium >10 mg/L (0.25 mmol/L) above upper limit of normal - this patient likely meets this criterion
• T-score ≤-2.5 at any skeletal site
• Vertebral fracture or low-energy fracture
• Kidney stones, nephrocalcinosis, or renal colic
• eGFR <60 mL/min/1.73m²
• 24-hour urine calcium >250 mg/day (women) or >300 mg/day (men)

Pre-Surgical Localization Imaging (only if surgery planned)

First-line approach: 1

• Parathyroid ultrasound PLUS functional imaging
• Functional imaging options:
  • Dual-isotope subtraction scintigraphy (¹²³I/⁹⁹ᵐTc-sestamibi) with SPECT/CT (reference standard)
  • OR ¹⁸F-choline PET/CT (excellent performance, preferred if multi-glandular disease suspected or patient <40 years old)

Common Pitfalls

1. Don't wait for "very high" PTH levels - 70% of PHPT patients have classic presentations, but 16% have PTH <65 pg/mL at some point, and 10% never have a high PTH value 2. The key is that PTH is inappropriately non-suppressed for the calcium level.

2. Don't assume normal calcium rules out PHPT - approximately 3% of surgical PHPT cases have both calcium and PTH in the reference range at times 4, 2

3. Don't forget to check FeCa - this distinguishes PHPT (FeCa >2%) from familial hypocalciuric hypercalcemia (FeCa ≤2%), which mimics PHPT but should not be operated on 1, 3

4. Vitamin D status matters - correct vitamin D deficiency before diagnosing atypical forms, but vitamin D deficiency cannot cause hypercalcemia 3