Primary Hyperparathyroidism: Diagnosis and Management
This patient has primary hyperparathyroidism (PHPT), characterized by elevated or inappropriately normal PTH in the presence of hypercalcemia with normal vitamin D levels. 1
Diagnostic Confirmation
The biochemical triad confirms PHPT:
- Elevated calcium with elevated or "inappropriately normal" PTH is diagnostic 1, 2
- Normal vitamin D (>30 ng/mL) excludes secondary hyperparathyroidism from vitamin D deficiency 1, 3
- The key concept: PTH should be suppressed when calcium is elevated; any detectable PTH in hypercalcemia is pathologic 2, 4
Complete the diagnostic workup with:
- Serum phosphorus (typically low-normal in PHPT) 2, 4
- 24-hour urine calcium or spot urine calcium/creatinine ratio to exclude familial hypocalciuric hypercalcemia (FHH) 1, 2
- If calcium/creatinine clearance ratio <0.01, consider FHH rather than PHPT 2
- Serum creatinine and eGFR to assess kidney function 1
- Bone density scan (DEXA) to evaluate for osteoporosis 1, 2
- Renal ultrasound to assess for nephrolithiasis or nephrocalcinosis 1
Management Algorithm
Step 1: Assess Surgical Candidacy
Surgery (parathyroidectomy) is the definitive treatment and should be pursued first 1, 5
Surgical indications include:
- Corrected calcium >1 mg/dL above upper limit of normal 1
- Impaired kidney function (GFR <60 mL/min/1.73 m²) 1
- Osteoporosis on DEXA 2
- History of nephrolithiasis or nephrocalcinosis 2, 4
- Age <50 years (per standard guidelines, though not explicitly in provided evidence)
Refer to endocrinology and an experienced parathyroid surgeon for evaluation 1
Step 2: Preoperative Localization (Only After Biochemical Diagnosis)
Critical pitfall: Never order parathyroid imaging before confirming biochemical diagnosis—imaging is for surgical planning, not diagnosis 1
- Obtain ultrasound and/or 99mTc-sestamibi scintigraphy with SPECT/CT if surgery is planned 1
Step 3: Medical Management (If Surgery Contraindicated or Declined)
Cinacalcet is FDA-approved for hypercalcemia in primary hyperparathyroidism when parathyroidectomy is indicated but patient cannot undergo surgery 5
Dosing protocol:
- Start cinacalcet 30 mg twice daily (note: higher than secondary hyperparathyroidism dosing) 5
- Titrate every 2-4 weeks through sequential doses: 30 mg BID → 60 mg BID → 90 mg BID → 90 mg TID or QID 5
- Goal: normalize serum calcium 5
- Contraindication: Do not initiate if serum calcium is below lower limit of normal 5
Monitoring on cinacalcet:
- Measure serum calcium within 1 week after initiation or dose adjustment 5
- Once stable, measure calcium every 2 months 5
- Watch for hypocalcemia (paresthesias, muscle spasms, QT prolongation) 5
Step 4: Conservative Management (Mild, Asymptomatic Disease)
If surgery is deferred and calcium is only mildly elevated:
- Ensure adequate oral hydration 1
- Discontinue calcium supplements, vitamin D supplements, and thiazide diuretics 1, 6
- Monitor serum calcium every 3 months 1
- Repeat bone density and renal imaging periodically 1
Critical Pitfalls to Avoid
Do not assume vitamin D deficiency is causing the elevated PTH - Normal vitamin D with hypercalcemia and elevated PTH = PHPT 1, 3
Do not supplement with vitamin D or calcium - This will worsen hypercalcemia 1, 6
Do not order parathyroid imaging before biochemical confirmation - Imaging cannot diagnose PHPT 1
Do not confuse with secondary hyperparathyroidism - Secondary HPT presents with hypocalcemia or normal calcium, not hypercalcemia 7
Recognize atypical presentations - Some patients have "normocalcemic PHPT" with high-normal calcium and inappropriately elevated PTH; these still require evaluation 3
In rare cases with severe bone disease (osteitis fibrosa cystica), hypercalcemia may suppress 1,25-dihydroxyvitamin D production - Normalizing calcium preoperatively can improve outcomes and reduce "hungry bone syndrome" postoperatively 8