What is the management approach for a patient with hyperparathyroidism (high Parathyroid Hormone (PTH) levels)?

Management of Elevated PTH

The management of elevated PTH requires first measuring serum calcium to distinguish primary hyperparathyroidism (elevated calcium) from secondary hyperparathyroidism (normal or low calcium), as this fundamentally determines the treatment approach. 1

Initial Diagnostic Workup

The following laboratory tests must be obtained to establish the etiology:

• Serum calcium (total and ionized) to differentiate primary from secondary hyperparathyroidism—elevated or high-normal calcium indicates primary disease, while low or low-normal calcium suggests secondary causes 1, 2
• Serum phosphorus, which is typically low in primary hyperparathyroidism and elevated in CKD-related secondary hyperparathyroidism 1
• 25-OH vitamin D levels, as deficiency is the most common reversible cause of secondary hyperparathyroidism, particularly in elderly patients 1, 2
• Kidney function (eGFR and creatinine), since PTH rises early in CKD, often before calcium or phosphorus abnormalities become apparent 1, 2
• Alkaline phosphatase if PTH is elevated, as this suggests high bone turnover and adds predictive value when interpreting PTH levels 3

Management Based on Underlying Cause

Vitamin D Deficiency (Most Common Reversible Cause)

• Supplement with cholecalciferol or ergocalciferol to achieve 25-OH vitamin D levels ≥30 ng/mL 1, 2
• Ensure adequate dietary calcium intake meeting age-related recommended dietary allowances, as low urinary calcium excretion suggests calcium deprivation 4, 2
• Recheck PTH every 3 months for 6 months, then every 3-6 months to assess response to vitamin D repletion 1, 2

CKD-Related Secondary Hyperparathyroidism

Critical: Do NOT start active vitamin D therapy (calcitriol) until serum phosphorus is below 4.6 mg/dL, as this worsens vascular calcification and increases calcium-phosphate product. 3

The management algorithm proceeds as follows:

1. Control hyperphosphatemia first through dietary phosphorus restriction to 800-1,000 mg/day and phosphate binders (calcium-based or non-calcium based) 1, 3
2. Target serum phosphorus between 3.5-5.5 mg/dL for stage 5 CKD patients 3
3. Address hypocalcemia with supplemental calcium carbonate 1-2 g three times daily with meals, serving dual purpose as phosphate binder and calcium supplement 3
4. Once phosphorus is controlled (<4.6 mg/dL), initiate active vitamin D therapy (calcitriol or paricalcitol) 3
5. Target PTH levels of 150-300 pg/mL for dialysis patients—NOT normal range, as suppressing PTH to <65 pg/mL causes adynamic bone disease with increased fracture risk 3

X-Linked Hypophosphatemia (XLH)

• Manage elevated PTH by increasing the dose of active vitamin D and/or decreasing the dose of oral phosphate supplements 4, 1
• In cases of persistent hypercalciuria and/or hypercalcemia, active vitamin D and phosphate supplements should be reduced or stopped 4
• Consider switching to burosumab therapy if available 4

Primary Hyperparathyroidism

• Parathyroidectomy is the only definitive cure and should be considered for patients younger than 50 years old or those with significant hypercalcemia, impaired renal function, renal stones, or osteoporosis 5, 6
• For patients unable to undergo surgery, cinacalcet 30 mg twice daily can be initiated and titrated every 2-4 weeks to normalize serum calcium levels 7

Medical Management for Refractory Cases

Calcimimetics (Cinacalcet)

Use cinacalcet with extreme caution, as it has been associated with severe adverse effects including hypocalcemia and QT interval prolongation. 4, 1

• For CKD patients on dialysis: Start cinacalcet 30 mg once daily, titrate 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 7
• For primary hyperparathyroidism or parathyroid carcinoma: Start cinacalcet 30 mg twice daily, titrate every 2-4 weeks up to 90 mg 3-4 times daily as necessary 7
• Cinacalcet is contraindicated if serum calcium is below the lower limit of normal 7
• NOT indicated for CKD patients not on dialysis due to increased risk of hypocalcemia 7

Monitoring During Cinacalcet Therapy

• Measure serum calcium and phosphorus within 1 week of initiation or dose adjustment 7
• If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, increase calcium-containing phosphate binders and/or vitamin D sterols 7
• If serum calcium falls below 7.5 mg/dL, withhold cinacalcet until serum calcium reaches 8 mg/dL, then reinitiate at next lowest dose 7

Surgical Management

Indications for Parathyroidectomy

• Persistent PTH >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy after 3-6 months of optimized treatment 3
• Persistent hypercalcemic hyperparathyroidism despite medical management 4
• Severe hyperparathyroidism with hypercalcemia that precludes medical therapy 3

Surgical Options

• Total parathyroidectomy (TPTX) may be superior to total parathyroidectomy with autotransplantation (TPTX+AT) with lower recurrence rates (OR 0.17,95% CI 0.06-0.54) 3
• Subtotal parathyroidectomy (SPTX) is another option 3

Post-Parathyroidectomy Care

• Monitor ionized calcium every 4-6 hours for the first 48-72 hours to prevent severe hypocalcemia 1, 3
• Initiate calcium gluconate infusion if ionized calcium falls below normal 1
• Administer calcium carbonate and calcitriol when oral intake is possible 1

Monitoring Schedule for Ongoing Management

CKD Patients

• CKD G3a-G3b: Measure calcium and phosphorus every 6-12 months 1
• CKD G4: Measure calcium and phosphorus every 3-6 months 1
• CKD G5/dialysis: Measure calcium and phosphorus every 1-3 months 1
• PTH levels: Every 3 months for 6 months, then every 3-6 months thereafter 1, 3

Primary Hyperparathyroidism

• Measure serum calcium every 2 months once maintenance dose established 7

Critical Pitfalls to Avoid

• Never assume PTH elevation alone indicates primary hyperparathyroidism—the calcium level is essential for proper classification 2
• Never start active vitamin D therapy when phosphorus exceeds 4.6 mg/dL (or 6.5 mg/dL in some protocols) due to risk of vascular calcification 3, 2
• Never over-suppress PTH in CKD patients to <65 pg/mL or <150 pg/mL in dialysis patients, as this causes adynamic bone disease 3, 2
• Never ignore alkaline phosphatase, as this marker adds predictive value for assessing bone turnover 3
• Never use cinacalcet in patients with serum calcium below the lower limit of normal 7
• Never use cinacalcet in CKD patients not on dialysis due to increased hypocalcemia risk 7