What is the management approach for a patient with elevated parathyroid hormone (PTH) levels, potentially due to primary hyperparathyroidism, vitamin D deficiency, or chronic kidney disease (CKD)?

Management of Elevated Parathyroid Hormone

The management of elevated PTH depends critically on distinguishing between primary hyperparathyroidism (with elevated or high-normal calcium), secondary hyperparathyroidism (with low or normal calcium due to vitamin D deficiency, low calcium intake, or CKD), and requires immediate assessment of serum calcium, phosphate, renal function (eGFR), and 25-OH vitamin D levels to guide treatment. 1, 2

Initial Diagnostic Workup

Measure the following simultaneously to determine etiology:

• Serum calcium (corrected for albumin) - Elevated or high-normal calcium with elevated PTH indicates primary hyperparathyroidism, while low or normal calcium suggests secondary hyperparathyroidism 1, 3
• Serum phosphate - Helps differentiate primary (often low phosphate) from secondary hyperparathyroidism (often elevated in CKD) 4, 2
• 25-OH vitamin D levels - Target >20 ng/mL; deficiency is the most common cause of secondary hyperparathyroidism and must be corrected before further intervention 1, 2
• Serum creatinine and eGFR - CKD is a major cause of secondary hyperparathyroidism and fundamentally changes management approach 1, 2
• 24-hour urinary calcium - Hypercalciuria (>300 mg/24h) may indicate primary hyperparathyroidism or renal calcium leak; low urinary calcium suggests calcium deprivation 1, 5

Management Based on Etiology

Primary Hyperparathyroidism (Elevated PTH + Elevated/High-Normal Calcium)

Parathyroidectomy is the only definitive cure and should be performed in symptomatic patients or those meeting surgical criteria. 2, 3

Surgical indications include: 2, 3

• Symptomatic disease (kidney stones, bone pain, fractures, neuromuscular symptoms)
• Osteoporosis on DEXA scan
• Impaired kidney function (GFR <60 mL/min/1.73 m²)
• Hypercalciuria

Preoperative localization with ultrasound and/or 99mTc-sestamibi scintigraphy with SPECT/CT is recommended, with minimally invasive parathyroidectomy (MIP) preferred when a single adenoma is confidently localized. 2, 3

For patients unable to undergo surgery: 6

• Cinacalcet 30 mg twice daily initially, 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
• Monitor serum calcium within 1 week after initiation or dose adjustment, then every 2 months once stable
• Critical caveat: Cinacalcet is contraindicated if serum calcium is below the lower limit of normal at initiation 6

Secondary Hyperparathyroidism Due to Vitamin D Deficiency (Normal Calcium, Elevated PTH)

Supplement with native vitamin D (cholecalciferol or ergocalciferol) to achieve 25-OH vitamin D levels >20 ng/mL. 1, 2

• Ensure adequate dietary calcium intake (adults >24 years: 950 mg/day minimum) 1
• Important consideration: In patients with coexistent primary hyperparathyroidism and vitamin D deficiency, vitamin D repletion does not typically exacerbate hypercalcemia and may decrease PTH levels by 24-26% and reduce bone turnover 7
• Monitor for hypercalciuria, as some patients may experience increased urinary calcium excretion after vitamin D repletion 7

Secondary Hyperparathyroidism in CKD (Not on Dialysis)

For CKD stages G3a-G5 not on dialysis with progressively rising or persistently elevated PTH above the upper normal limit, evaluate and correct modifiable factors: 4, 2

• Hyperphosphatemia - Implement dietary phosphorus restriction and phosphate binders if phosphate is progressively or persistently elevated 4, 2
• Hypocalcemia - Provide calcium supplementation as needed 4, 2
• High phosphate intake - Dietary counseling for phosphorus restriction 4, 2
• Vitamin D deficiency - Supplement with native vitamin D to achieve 25-OH vitamin D >20 ng/mL 4, 2

Restrict the dose of calcium-based phosphate binders in adult patients with CKD G3a-G5D to minimize vascular calcification risk. 4, 2

Calcitriol and vitamin D analogs should NOT be routinely used in CKD G3a-G5 not on dialysis. 4, 2 Reserve these agents only for patients with CKD G4-G5 with severe and progressive hyperparathyroidism despite correction of modifiable factors. 4, 2

Critical limitation: The optimal PTH level in CKD G3a-G5 not on dialysis is not known, so avoid aggressive PTH suppression. 4

Secondary Hyperparathyroidism in CKD on Dialysis (G5D)

Target intact PTH levels in the range of approximately 2-9 times the upper normal limit for the assay (approximately 150-300 pg/mL). 4, 2

For patients requiring PTH-lowering therapy: 4, 2, 6

• First-line options: Calcimimetics (cinacalcet), calcitriol, vitamin D analogs (paricalcitol, doxercalciferol), or combination therapy 4, 2
• Cinacalcet dosing: Start at 30 mg once daily, 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 6
• Intermittent intravenous calcitriol is more effective than daily oral calcitriol for lowering PTH 2

Monitoring requirements for dialysis patients on active vitamin D or calcimimetics: 2, 6

• Serum calcium and phosphorus every 2 weeks for 1 month after initiation or dose adjustment, then monthly
• PTH monthly for at least 3 months, then every 3 months once target achieved
• Assess iPTH no earlier than 12 hours after cinacalcet dosing 6

Management of hypocalcemia during treatment: 6

• 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
• If serum calcium falls below 7.5 mg/dL or symptoms of hypocalcemia persist: withhold cinacalcet until serum calcium reaches 8 mg/dL and symptoms resolve, then reinitiate at the next lowest dose

Use dialysate calcium concentration between 1.25-1.50 mmol/L (2.5-3.0 mEq/L) to help maintain calcium balance. 4

Refractory Secondary Hyperparathyroidism Requiring Surgery

Consider parathyroidectomy for patients with severe hyperparathyroidism (persistent intact PTH >800 pg/mL) associated with hypercalcemia and/or hyperphosphatemia refractory to medical therapy. 4, 2, 3

Surgical options: 2, 3

• Total parathyroidectomy (TPTX) - Superior regarding recurrence rates (OR = 0.20) and lower reoperation rates (OR = 0.17), but higher risk of permanent hypoparathyroidism (OR = 2.97) 3
• Total parathyroidectomy with autotransplantation (TPTX + AT)
• Subtotal parathyroidectomy

Post-parathyroidectomy management is critical to prevent hungry bone syndrome: 2

• Monitor ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable
• If ionized calcium falls below 0.9 mmol/L: initiate calcium gluconate infusion at 1-2 mg elemental calcium/kg/hour
• When oral intake possible: calcium carbonate 1-2 g three times daily and calcitriol up to 2 μg/day
• Adjust or discontinue phosphate binders based on serum phosphorus levels

Critical Pitfalls to Avoid

• Never use cinacalcet in CKD patients not on dialysis - Increased risk of hypocalcemia compared to dialysis patients due to lower baseline calcium levels 6
• Do not initiate cinacalcet if serum calcium is below the lower limit of normal - This is an absolute contraindication 6
• Avoid aggressive PTH suppression in CKD not on dialysis - Can lead to adynamic bone disease 4, 2
• Do not overlook vitamin D deficiency - This is the most common reversible cause of elevated PTH and must be corrected first 1, 2, 5
• Be cautious with calcium-based phosphate binders - Restrict doses to minimize vascular calcification risk 4, 2
• Monitor for hypocalcemia-induced QT prolongation - Patients with congenital long QT syndrome, history of QT prolongation, or conditions predisposing to arrhythmias are at increased risk when treated with calcimimetics 6