Management of Hyperparathyroidism
Primary Hyperparathyroidism (PHPT)
Surgery is the only definitive cure for primary hyperparathyroidism, and parathyroidectomy should be considered in all patients with PHPT. 1, 2
Surgical Indications
Parathyroidectomy is indicated when any of the following criteria are met: 3
- Symptomatic disease (bone pain, kidney stones, neurocognitive symptoms)
- Age ≤50 years
- Serum calcium >1 mg/dL above upper limit of normal
- Osteoporosis (T-score ≤-2.5 at any site)
- Creatinine clearance <60 mL/min/1.73 m²
- Nephrolithiasis or nephrocalcinosis
- Hypercalciuria (>400 mg/24 hours)
Surgical Approaches
Minimally invasive parathyroidectomy (MIP) is preferred when preoperative imaging confidently localizes a single adenoma, offering shorter operative times, faster recovery, and lower costs compared to bilateral neck exploration. 4, 1, 2
- MIP requires confident preoperative localization using ultrasound and/or 99mTc-sestamibi SPECT/CT, plus intraoperative PTH monitoring to confirm removal of hyperfunctioning tissue 4, 1
- Bilateral neck exploration (BNE) remains necessary for discordant/nonlocalizing imaging or suspected multigland disease 4, 1
- Most patients (>80%) have a single adenoma, making MIP feasible in the majority 4
Medical Management for Non-Surgical Candidates
For patients who decline or cannot undergo surgery: 5
Calcium intake:
- Do NOT restrict dietary calcium—follow standard population guidelines (1000-1200 mg/day) 5
- Calcium restriction paradoxically worsens PTH secretion 5
Vitamin D repletion:
- Target 25-hydroxyvitamin D ≥50 nmol/L (20 ng/mL) minimum, preferably ≥75 nmol/L (30 ng/mL) 5, 2
- Measure 25-OH vitamin D levels to exclude concomitant vitamin D deficiency 2
Pharmacologic options:
For hypercalcemia control: Cinacalcet 30 mg twice daily, titrated every 2-4 weeks up to 90 mg 3-4 times daily to normalize serum calcium 6, 5
For bone density improvement: Alendronate (bisphosphonate) increases lumbar spine BMD without affecting serum calcium 5
Combination therapy with cinacalcet plus bisphosphonate is reasonable when both hypercalcemia control and BMD improvement are needed, though strong evidence is limited 5
Reoperative Cases
Preoperative imaging is essential before repeat parathyroid surgery to localize target lesions and identify postoperative anatomic changes. 4, 1
Secondary Hyperparathyroidism (SHPT)
Secondary hyperparathyroidism in CKD requires a stepwise approach prioritizing phosphate control BEFORE initiating active vitamin D therapy to prevent vascular calcification. 7
Step 1: Control Hyperphosphatemia FIRST
Critical pitfall: Never start active vitamin D therapy with uncontrolled hyperphosphatemia (>4.6 mg/dL), as this dramatically worsens vascular calcification and increases calcium-phosphate product. 7
- Target serum phosphorus 3.5-5.5 mg/dL for stage 5 CKD 7
- Dietary phosphorus restriction to 800-1,000 mg/day (maintain adequate protein 1.0-1.2 g/kg/day for dialysis patients) 7
- Phosphate binders: calcium carbonate 1-2 g three times daily with meals (dual purpose as calcium supplement) 7
- Monitor phosphorus monthly after initiating therapy 7
Step 2: Address Hypocalcemia
- Supplemental calcium carbonate 1-2 g three times daily with meals 7
- Monitor calcium within 1 week of initiating therapy 7
Step 3: Vitamin D Therapy (Only After Phosphorus <4.6 mg/dL)
Target PTH 150-300 pg/mL for stage 5 CKD/dialysis patients—NOT normal range. 7
Critical pitfall: Targeting normal PTH levels (<65 pg/mL) in dialysis patients causes adynamic bone disease with increased fracture risk. 7
- For hemodialysis patients: Intermittent IV calcitriol or paricalcitol is more effective than oral administration 7, 8
- For peritoneal dialysis patients: Oral calcitriol 0.5-1.0 μg or doxercalciferol 2.5-5.0 μg given 2-3 times weekly 1
- Adjust dosage according to severity of hyperparathyroidism 7
- Monitor calcium and phosphorus every 2 weeks for 1 month after initiation/dose increase, then monthly 1
- Monitor PTH monthly for at least 3 months, then every 3 months once target achieved 1
- Discontinue all vitamin D therapy if calcium rises above 10.2 mg/dL 7
Step 4: Calcimimetics for Persistent Elevation
If PTH remains elevated despite optimized vitamin D therapy: 7
- Add cinacalcet 30 mg once daily, titrated every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily 6
- Alternative calcimimetics: etelcalcetide, evocalcet, or upacicalcet 7
- Monitor serum calcium within 1 week and iPTH 1-4 weeks after initiation or dose adjustment 6
- If calcium falls below 8.4 mg/dL, increase calcium-based phosphate binders and/or vitamin D sterols 6
- If calcium falls below 7.5 mg/dL, withhold cinacalcet until calcium reaches 8 mg/dL, then restart at next lowest dose 6
Step 5: Surgical Management
Parathyroidectomy is indicated for severe refractory SHPT: persistent PTH >800 pg/mL with hypercalcemia and/or hyperphosphatemia despite 3-6 months of optimized medical therapy. 7, 1
- Total parathyroidectomy (TPTX) has lower recurrence rates (OR 0.17,95% CI 0.06-0.54) and shorter operative time compared to TPTX with autotransplantation 7
- TPTX carries higher risk of hypoparathyroidism (OR 2.97,95% CI 1.09-8.08) but studies show no permanent hypocalcemia or adynamic bone disease 7
- Avoid total parathyroidectomy in patients who may receive kidney transplant, as calcium control becomes problematic post-transplant 1
- Subtotal parathyroidectomy or TPTX with autotransplantation are alternatives 1
Postoperative Management
Monitor ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable. 7, 1, 2
- Initiate calcium gluconate infusion if calcium falls below normal 1, 2
- Provide calcium carbonate and calcitriol when oral intake possible 2
- Adjust phosphate binders based on serum phosphorus levels 1, 2
- "Hungry bone syndrome" can cause late-onset hypocalcemia as bone rapidly remineralizes—maintain aggressive calcium/vitamin D supplementation 2
Tertiary Hyperparathyroidism (THPT)
Tertiary hyperparathyroidism occurs after longstanding SHPT when autonomous PTH secretion develops, causing hypercalcemia despite correction of underlying stimulus (typically post-kidney transplant). 9
- Surgical excision is recommended for medically refractory cases 4
- Imaging goal is to identify all eutopic and potential ectopic/supernumerary glands due to typical multigland disease 4
Monitoring Summary
For SHPT on dialysis: 7
- Calcium and phosphorus: monthly initially, then every 1-3 months
- PTH: every 3-6 months
- 25-hydroxyvitamin D: annually
- Alkaline phosphatase: every 3-6 months if PTH elevated
For PHPT on medical management: 5
- Calcium: every 2 months
- BMD: annually
- Renal imaging: as clinically indicated for stone surveillance