What is the management approach for intact Parathyroid Hormone (PTH) elevation?

Management of Intact PTH Elevation

The management of elevated intact PTH depends critically on identifying whether this represents primary hyperparathyroidism (elevated or inappropriately normal calcium), secondary hyperparathyroidism (normal or low calcium with identifiable cause), or chronic kidney disease-related mineral bone disorder, with treatment ranging from addressing underlying causes to active vitamin D therapy or surgical intervention based on the specific etiology and severity. 1

Initial Diagnostic Evaluation

The first step is measuring serum calcium, phosphorus, 25-OH vitamin D, and kidney function to determine the underlying cause 1:

• If calcium is elevated or high-normal with elevated PTH: This indicates primary hyperparathyroidism 2
• If calcium is normal or low with elevated PTH: Evaluate for secondary causes 1
• If chronic kidney disease is present: Stage-specific PTH targets apply 3

Review all medications that affect calcium metabolism, including thiazide diuretics, lithium, calcium supplements, and vitamin D 1, 4

Management Based on CKD Stage

CKD Stage 3 (eGFR 30-59 mL/min/1.73m²)

Target PTH: 35-70 pg/mL 3

When PTH exceeds 70 pg/mL on two consecutive measurements 3:

• Restrict dietary phosphate intake first 3
• Ensure 25-OH vitamin D levels ≥30 ng/mL with cholecalciferol or ergocalciferol supplementation 1
• If PTH remains elevated despite vitamin D repletion, initiate active vitamin D sterol (calcitriol, alfacalcidol, or doxercalciferol) only if corrected calcium <9.5 mg/dL and phosphorus <4.6 mg/dL 3
• Starting dose: calcitriol 0.25 mcg daily or doxercalciferol 2.5 mcg daily 3

CKD Stage 4 (eGFR 15-29 mL/min/1.73m²)

Target PTH: 70-110 pg/mL 3

When PTH exceeds 110 pg/mL on two consecutive measurements 3:

• Same approach as Stage 3 with dietary phosphate restriction 3
• Ensure vitamin D repletion to ≥30 ng/mL 1
• Initiate active vitamin D sterol if corrected calcium <9.5 mg/dL and phosphorus <4.6 mg/dL 3

CKD Stage 5 (Dialysis)

Target PTH: 150-300 pg/mL 3

When PTH exceeds 300 pg/mL 3:

• Initiate active vitamin D sterol (calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) 3
• Intravenous calcitriol is more effective than oral for lowering PTH 3
• Starting dose for hemodialysis: calcitriol 0.5-1.0 mcg IV three times weekly after dialysis 3
• Starting dose for peritoneal dialysis: calcitriol 0.5-1.0 mcg orally 2-3 times weekly 3
• If calcium or phosphorus are above target, consider paricalcitol or doxercalciferol as alternatives 3

Critical safety parameters for vitamin D therapy 3:

• Do not initiate if corrected calcium ≥9.5 mg/dL 3
• Do not initiate if phosphorus ≥4.6 mg/dL (CKD 3-4) or ≥6.5 mg/dL (Stage 5) 3
• Hold therapy if calcium exceeds 9.5 mg/dL; resume at half dose when calcium <9.5 mg/dL 3
• Hold therapy if phosphorus rises above target; increase phosphate binders, then resume 3

Management of Primary Hyperparathyroidism

Indications for Parathyroidectomy

Surgery is indicated when 1, 5:

• Persistent PTH >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 1
• Symptomatic disease including recurrent renal stones, bone disease, or fractures 1, 5
• Serum calcium >1 mg/dL above upper normal limit in patients <50 years old 2

Surgical options 1, 5:

• Subtotal parathyroidectomy (removes 3.5 glands) 1
• Total parathyroidectomy with autotransplantation 1

Medical Management for Non-Surgical Candidates

For patients with primary hyperparathyroidism who cannot undergo surgery 6:

• Cinacalcet 30 mg twice daily, titrated every 2-4 weeks through 60 mg twice daily, 90 mg twice daily, up to 90 mg 3-4 times daily to normalize calcium 6
• Must be taken with food or shortly after meals 6
• Monitor calcium within 1 week after initiation or dose adjustment 6
• Contraindicated if calcium is below lower limit of normal 6

Monitoring Requirements

CKD Stages 3-4 on Active Vitamin D 3

• Calcium and phosphorus: Monthly for first 3 months, then every 3 months 3
• PTH: Every 3 months for 6 months, then every 3 months thereafter 3

CKD Stage 5 on Active Vitamin D 3

• Calcium and phosphorus: Every 2 weeks for 1 month, then monthly 3
• PTH: Monthly for 3 months, then every 3 months once target achieved 3

Primary Hyperparathyroidism 1

• Calcium and phosphorus: Monthly for first 3 months, then every 3 months 1
• PTH: Every 3 months for 6 months, then every 3-6 months 1

Critical Pitfalls to Avoid

Risk of adynamic bone disease: Oversuppression of PTH below 100 pg/mL in dialysis patients (or below 65 pg/mL) causes adynamic bone with loss of calcium buffering capacity, increased hypercalcemia risk, and potentially increased vascular calcification 3. If PTH falls below target range, hold vitamin D therapy until PTH rises, then resume at half the previous dose 3.

Hypocalcemia with vitamin D therapy: Life-threatening events including prolonged QT interval, seizures, hypotension, and arrhythmias have been reported 6. In dialysis patients, if calcium falls to 7.5-8.4 mg/dL, increase calcium-based phosphate binders and vitamin D sterols; if calcium falls below 7.5 mg/dL, withhold cinacalcet or active vitamin D until calcium reaches 8 mg/dL, then restart at lower dose 6.

PTH levels between 100-500 pg/mL in CKD have insufficient sensitivity and specificity to predict bone disease type; bone biopsy may be needed if unexplained hypercalcemia, bone pain, or elevated bone alkaline phosphatase develops 1.

Do not delay surgery in patients with recurrent renal stones and hyperparathyroidism, as progressive renal damage occurs 1, 5.

Dialysate calcium concentration should be 2.5 mEq/L (1.25 mmol/L) to minimize calcium loading while using calcium-based phosphate binders and vitamin D 3.