What is the recommended treatment for a patient with elevated parathyroid hormone levels and potential primary or secondary hyperparathyroidism?

Management of Elevated Parathyroid Hormone

The first critical step is to simultaneously measure serum calcium and intact PTH to distinguish between primary, secondary, and tertiary hyperparathyroidism, as this determines whether surgical or medical management is appropriate. 1, 2

Initial Diagnostic Algorithm

Measure these labs simultaneously:

• Serum calcium (corrected for albumin if albumin is abnormal) and ionized calcium 2
• Intact parathyroid hormone (iPTH) using EDTA plasma, not serum 2
• 25-hydroxyvitamin D levels 1, 2
• Serum phosphorus 2
• Serum creatinine and estimated GFR 2
• 24-hour urine calcium or spot urine calcium/creatinine ratio 2

Critical interpretation points:

• PTH assays vary by up to 47% between different generations, so use assay-specific reference values 2
• PTH biological variation is substantial (20% in healthy individuals), requiring differences >54% to be clinically significant 2
• Sample PTH in EDTA plasma at 4°C for most stable results 2

Differential Diagnosis Based on Calcium and PTH

Primary Hyperparathyroidism (Elevated PTH + Elevated Calcium)

This is the most common scenario requiring surgical evaluation. 2, 3

Confirm the diagnosis by:

• Elevated or inappropriately normal PTH with hypercalcemia (calcium >10.2 mg/dL) 2
• Corrected calcium >0.25 mmol/L (approximately 1 mg/dL) above upper limit of normal indicates more severe disease 2
• Exclude vitamin D deficiency (aim for 25-OH vitamin D >20 ng/mL) as this causes secondary hyperparathyroidism 1, 2

Surgical indications - refer to endocrinology and high-volume parathyroid surgeon if ANY of the following: 2, 3, 4

• Corrected calcium >1 mg/dL above upper limit of normal
• Age <50 years
• eGFR <60 mL/min/1.73 m² (even with mild calcium elevation)
• Osteoporosis (T-score ≤-2.5 at any site)
• History of nephrolithiasis or nephrocalcinosis
• Hypercalciuria (>300 mg/24hr)
• Symptomatic disease (bone pain, kidney stones, neuropsychiatric symptoms)

Parathyroidectomy is the only definitive cure and should not be delayed in symptomatic patients. 3, 5

For non-surgical candidates only: 2

• Maintain normal calcium intake (1000-1200 mg/day, not exceeding 2000 mg/day total) 2
• Ensure 25-OH vitamin D >20 ng/mL with supplementation if needed 2
• Consider cinacalcet 30 mg twice daily, titrated every 2-4 weeks to normalize calcium 6

Secondary Hyperparathyroidism (Elevated PTH + Normal or Low Calcium)

This requires medical management, NOT surgery. 1, 7

Treatment algorithm: 1

1. Correct vitamin D deficiency first:

   • Supplement with cholecalciferol or ergocalciferol if 25-OH vitamin D <30 ng/mL 1
   • Target 25-OH vitamin D >20 ng/mL (50 mmol/L) 1, 3
   • Do NOT supplement vitamin D if calcium >10.2 mg/dL 2

2. Ensure adequate dietary calcium:

   • Assess dietary intake and ensure age-appropriate recommendations are met 1
   • Avoid both high and low calcium diets 2

3. For CKD-related secondary hyperparathyroidism:

   • Increase active vitamin D (calcitriol or alfacalcidol) 1
   • Decrease oral phosphate supplements if PTH remains elevated 1
   • Implement dietary phosphate restriction 3
   • Use non-calcium-based phosphate binders if needed 3

4. For refractory cases:

   • Consider cinacalcet 30 mg once daily for CKD patients on dialysis, titrated every 2-4 weeks to target iPTH 150-300 pg/mL 6, 7
   • Cinacalcet is contraindicated in CKD patients NOT on dialysis due to hypocalcemia risk 6

5. Manage hypercalciuria if present:

   • Increase water intake to achieve urine volume ≥2.5 liters daily 1
   • Administer potassium citrate (NOT sodium citrate, which increases urinary calcium) 1
   • Limit sodium intake 1

Tertiary Hyperparathyroidism (Elevated PTH + Elevated Calcium Despite Treating Secondary Cause)

This represents autonomous PTH secretion after long-standing secondary hyperparathyroidism. 5, 7

Management approach:

• Consider parathyroidectomy for persistent hypercalcemic hyperparathyroidism despite optimized medical therapy 1
• Calcimimetics may be used as a bridge or alternative if surgery is not feasible 1, 7

Critical Monitoring Parameters

For patients on medical management: 1, 2

• Serum calcium and phosphorus every 3 months (more frequently if GFR <30 mL/min/1.73 m²) 2
• PTH levels every 3-6 months 8
• 24-hour urine calcium to assess treatment efficacy 1
• Renal ultrasound to screen for nephrocalcinosis or stones 2

For patients on cinacalcet: 6

• Serum calcium within 1 week after initiation or dose adjustment
• iPTH 1-4 weeks after initiation or dose adjustment
• Monthly calcium monitoring once maintenance dose established

Common Pitfalls to Avoid

Do not:

• Order parathyroid imaging before confirming biochemical diagnosis - imaging is for surgical planning only 2
• Supplement with vitamin D if calcium >10.2 mg/dL, as this worsens hypercalcemia 2
• Use high-dose phosphate supplements (>80 mg/kg daily), which worsen hyperparathyroidism 1
• Delay surgical referral in symptomatic primary hyperparathyroidism or those meeting surgical criteria 3
• Use cinacalcet in CKD patients not on dialysis 6
• Assume normal PTH excludes primary hyperparathyroidism - inappropriately normal PTH with hypercalcemia still indicates primary disease 2

Special consideration for growth hormone therapy:

• Withhold GH treatment if PTH >500 pg/mL and reinstitute only when PTH returns to target range 8
• Adequately treat CKD-MBD before initiating GH therapy 8