What are the appropriate diagnostic steps and treatments for abnormal parathyroid hormone (PTH) levels?

Management of Abnormal Parathyroid Hormone (PTH) Levels

The appropriate diagnostic and treatment approach for abnormal PTH levels should be based on the severity of hyperparathyroidism, underlying kidney function, and associated calcium and phosphorus abnormalities.

Diagnostic Evaluation

• Measure serum calcium, phosphorus, and PTH levels to establish baseline values and determine the type of PTH abnormality 1
• For patients with CKD, the frequency of monitoring should be based on CKD stage:
  • CKD G3a-G3b: Calcium and phosphorus every 6-12 months; PTH once with follow-up based on baseline level 1
  • CKD G4: Calcium and phosphorus every 3-6 months; PTH every 6-12 months 1
  • CKD G5/dialysis: Calcium and phosphorus every 1-3 months; PTH every 3-6 months 1
• Consider bone biopsy in patients with PTH levels between 100-500 pg/mL who develop unexplained hypercalcemia, bone pain, or increased bone alkaline phosphatase activity 1

Management of Secondary Hyperparathyroidism in CKD

Non-Dialysis CKD Patients (G3a-G5)

• For patients with progressively rising or persistently elevated PTH above normal range, evaluate for modifiable factors including:
  • Hyperphosphatemia
  • Hypocalcemia
  • High phosphate intake
  • Vitamin D deficiency 1
• Calcitriol and vitamin D analogs should not be routinely used in CKD G3a-G5 non-dialysis patients 1
• Reserve calcitriol and vitamin D analogs for CKD G4-G5 patients with severe and progressive hyperparathyroidism 1

Dialysis Patients (CKD G5D)

• For dialysis patients with PTH levels >300 pg/mL (33.0 pmol/L), administer active vitamin D sterols (calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) to reduce PTH to a target range of 150-300 pg/mL (16.5-33.0 pmol/L) 1
• Intermittent intravenous administration of calcitriol is more effective than daily oral calcitriol in lowering serum PTH levels 1
• For patients with elevated calcium or phosphorus levels, consider alternative vitamin D analogs such as paricalcitol or doxercalciferol 1
• Target maintaining intact PTH levels in the range of approximately 2-9 times the upper normal limit for the assay 1
• Monitor calcium and phosphorus every 2 weeks for 1 month after initiating or increasing vitamin D sterol dose, then monthly thereafter 1
• Monitor PTH monthly for at least 3 months and then every 3 months once target levels are achieved 1

Management Based on Calcium and Phosphorus Levels

• Avoid hypercalcemia in all CKD patients 1
• For dialysis patients, use a dialysate calcium concentration between 1.25 and 1.50 mmol/L (2.5 and 3.0 mEq/L) 1
• Base phosphate-lowering treatment decisions on progressively or persistently elevated serum phosphate 1
• Restrict the dose of calcium-based phosphate binders in adult CKD patients receiving phosphate-lowering treatment 1

Pharmacological Management Options

• For dialysis patients requiring PTH-lowering therapy, options include:
  • Calcimimetics (cinacalcet)
  • Calcitriol
  • Vitamin D analogs
  • Combination of calcimimetics with calcitriol or vitamin D analogs 1
• Cinacalcet starting dose is 30 mg once daily with food, titrated every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily to target iPTH levels of 150-300 pg/mL 2
• Monitor serum calcium frequently during dose titration of cinacalcet 2

Management of Adynamic Bone Disease

• For patients with adynamic bone disease (PTH <100 pg/mL), allow plasma levels of intact PTH to rise to increase bone turnover 1
• This can be accomplished by decreasing doses of calcium-based phosphate binders and vitamin D or eliminating such therapy 1

Surgical Management

• Recommend parathyroidectomy for patients with severe hyperparathyroidism (persistent serum levels of intact PTH >800 pg/mL [88.0 pmol/L]) associated with hypercalcemia and/or hyperphosphatemia that are refractory to medical therapy 1
• Effective surgical options include subtotal parathyroidectomy or total parathyroidectomy with parathyroid tissue autotransplantation 1
• Consider bone biopsy prior to parathyroid ablative therapy in patients with PTH levels less than 800-1,000 pg/mL to document hyperparathyroidism 1
• Perform imaging of parathyroid glands with 99 Tc-Sestamibi scan, ultrasound, CT scan, or MRI prior to re-exploration parathyroid surgery 1

Post-Parathyroidectomy Management

• Measure ionized calcium every 4-6 hours for the first 48-72 hours after surgery, then twice daily until stable 1
• If ionized calcium falls below normal (<0.9 mmol/L), initiate calcium gluconate infusion at 1-2 mg elemental calcium per kg body weight per hour 1
• When oral intake is possible, administer calcium carbonate 1-2 g three times daily and calcitriol up to 2 μg/day 1
• Adjust or discontinue pre-surgery phosphate binders based on serum phosphorus levels 1

Common Pitfalls and Caveats

• PTH levels between 100-500 pg/mL have insufficient sensitivity and specificity to reliably predict adynamic bone disease or hyperparathyroidism 1
• Aluminum toxicity must be excluded prior to parathyroidectomy to avoid worsening of aluminum bone disease 1
• Inappropriate parathyroid ablation in patients with PTH levels less than 800 pg/mL can induce hypoparathyroidism and adynamic bone disease 1
• Monitoring parathyroid gland size by ultrasonography can be a useful marker for the long-term prognosis of calcitriol pulse therapy in chronic dialysis patients 3