What is the evaluation and treatment approach for a patient with hyperparathyroidism (primary or secondary), considering factors such as serum calcium, phosphate, and parathyroid hormone (PTH) levels, kidney function, and vitamin D status?

Evaluation and Treatment of Hyperparathyroidism

Initial Diagnostic Evaluation

Measure serum calcium, phosphate, intact PTH, 25-hydroxyvitamin D, and creatinine/eGFR to differentiate primary from secondary hyperparathyroidism and guide treatment decisions. 1, 2

Key Laboratory Distinctions

• Primary hyperparathyroidism presents with elevated or high-normal calcium alongside elevated PTH, typically requiring parathyroidectomy for symptomatic disease 3
• Secondary hyperparathyroidism shows elevated PTH with normal or low calcium, driven by vitamin D deficiency, hyperphosphatemia, or chronic kidney disease 2, 4
• Measure 25-OH vitamin D levels targeting >20 ng/mL (ideally >30 ng/mL), as deficiency commonly causes secondary hyperparathyroidism 1, 2
• Calculate eGFR to determine CKD stage, as this fundamentally changes management algorithms 1, 2
• Check alkaline phosphatase when PTH is elevated, as rising levels suggest progressive bone disease and high bone turnover 2

Critical Timing Considerations

• Begin measuring calcium, phosphorus, and intact PTH when GFR falls below 60 mL/min/1.73 m², as PTH elevation can develop at this early stage 2
• Use serial PTH measurements over 3 months rather than single values to guide treatment decisions, as trends matter more than isolated readings 2

Management of Primary Hyperparathyroidism

Parathyroidectomy is the definitive treatment for symptomatic primary hyperparathyroidism and should be offered to asymptomatic patients meeting surgical criteria. 3

Surgical Indications

• Symptomatic disease (nephrolithiasis, skeletal complications, neuromuscular symptoms) warrants surgery 3
• Asymptomatic patients meeting guideline criteria should be offered surgery 3
• Surgery can be considered even when criteria are not met if the patient prefers definitive treatment 3

Medical Management When Surgery Not Appropriate

• Cinacalcet starting at 30 mg twice daily, titrated every 2-4 weeks through sequential doses (30 mg BID → 60 mg BID → 90 mg BID → 90 mg TID-QID) to normalize serum calcium 5
• Measure serum calcium within 1 week after initiation or dose adjustment 5
• Monitor serum calcium every 2 months once maintenance dose established 5

Management of Secondary Hyperparathyroidism

Non-Dialysis CKD (Stages 3-4)

For CKD stages 3-4, correct vitamin D deficiency and control hyperphosphatemia before considering active vitamin D therapy, as premature calcitriol use with elevated phosphate dramatically increases vascular calcification risk. 6, 2

Step 1: Vitamin D Repletion

• Supplement with ergocalciferol 50,000 IU monthly if 25(OH)D <30 ng/mL 2, 7
• Recheck 25(OH)D annually once replete 7
• This addresses the most common reversible cause of secondary hyperparathyroidism 2

Step 2: Phosphate Control

• Initiate dietary phosphorus restriction to 800-1,000 mg/day while maintaining adequate protein intake (1.0-1.2 g/kg/day for dialysis patients) 2
• Target serum phosphorus within normal range (2.7-4.6 mg/dL for stage 3.5-5.5 mg/dL for stage 5) 6, 2
• Use calcium carbonate 1-2 g three times daily with meals as dual-purpose phosphate binder and calcium supplement 2
• Never initiate active vitamin D therapy until serum phosphorus falls below 4.6 mg/dL 2

Step 3: Active Vitamin D Therapy (CKD Stage 4-5 Only)

• Reserve calcitriol for CKD G4-G5 patients with severe, progressive hyperparathyroidism despite vitamin D repletion and phosphate control 2, 7
• Do not target normal PTH levels (<65 pg/mL) in advanced CKD, as this causes adynamic bone disease with increased fracture risk 6, 2
• For stage 3 CKD, avoid routine calcitriol unless PTH continues rising despite optimization 2

Dialysis Patients (CKD Stage 5D)

For hemodialysis or peritoneal dialysis patients with intact PTH >300 pg/mL, administer active vitamin D sterols to reduce PTH to target range of 150-300 pg/mL, with intermittent intravenous calcitriol being more effective than daily oral administration. 6, 1

Initial Therapy Selection

• Start with active vitamin D sterols (calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) 6
• Intermittent intravenous calcitriol is more effective than daily oral calcitriol for lowering PTH 6, 1
• For peritoneal dialysis, use oral calcitriol 0.5-1.0 μg or doxercalciferol 2.5-5.0 μg given 2-3 times weekly 6
• Adjust dosage according to severity: larger doses required when intact PTH exceeds 500-600 pg/mL, and even higher doses when PTH >1,000 pg/mL 6

Monitoring Schedule

• Measure serum calcium and phosphorus every 2 weeks for 1 month after initiation or dose adjustment, then monthly 6, 1
• Measure PTH monthly for at least 3 months, then every 3 months once target achieved 6, 1
• Reduce or temporarily discontinue vitamin D if serum calcium rises above normal range 2

Second-Line Therapy: Calcimimetics

• Add cinacalcet 30 mg once daily if PTH remains elevated despite optimized vitamin D therapy 5, 8
• Titrate no more frequently than every 2-4 weeks through sequential doses (30 → 60 → 90 → 120 → 180 mg once daily) to target iPTH 150-300 pg/mL 5
• Measure serum calcium within 1 week and iPTH 1-4 weeks after initiation or dose adjustment 5
• If serum calcium falls below 8.4 mg/dL, increase calcium-containing phosphate binders and/or vitamin D sterols 5
• If serum calcium falls below 7.5 mg/dL, withhold cinacalcet until calcium reaches 8 mg/dL, then reinitiate at next lowest dose 5

Surgical Management

• Consider parathyroidectomy if PTH remains persistently >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy after 3-6 months of optimized treatment 2
• Total parathyroidectomy (TPTX) may be superior to TPTX with autotransplantation, showing lower recurrence rates (OR 0.17,95% CI 0.06-0.54) and shorter operative time, though with higher risk of hypoparathyroidism (OR 2.97,95% CI 1.09-8.08) 2
• Monitor ionized calcium every 4-6 hours for first 48-72 hours post-operatively, then twice daily until stable 2

Critical Pitfalls to Avoid

• Never start vitamin D therapy with uncontrolled hyperphosphatemia, as this worsens vascular calcification and increases calcium-phosphate product (should never exceed 70 mg²/dL²) 6, 2
• Never target normal PTH levels in dialysis patients, as suppression to <65 pg/mL causes adynamic bone disease with increased fracture risk 6, 2
• Never use calcium-based phosphate binders when hypercalcemia is present 6, 7
• Recognize that intact PTH assays overestimate biologically active PTH by detecting C-terminal fragments, so use assay-specific reference values 2
• In elderly patients post-parathyroidectomy, avoid initiating active vitamin D therapy at CKD stage 3a if 25(OH)D levels are adequate, as routine use is not recommended at this stage 7