What is the best course of action for a patient with hypercalcemia and elevated Parathyroid Hormone (PTH) levels, potentially indicating hyperparathyroidism?

Management of Elevated Calcium and PTH

For a patient with hypercalcemia and elevated PTH, parathyroidectomy is the only curative treatment and should be performed in patients meeting surgical criteria, including symptomatic disease (kidney stones, bone pain, fractures), osteoporosis on DEXA scan, impaired kidney function (GFR < 60 mL/min/1.73 m²), or severe hypercalcemia. 1

Diagnostic Confirmation

The combination of hypercalcemia with elevated or inappropriately normal PTH confirms primary hyperparathyroidism (PHPT), as PTH should be suppressed in the presence of hypercalcemia from other causes. 2, 3

Critical initial steps:

• Measure serum calcium (corrected for albumin) and intact PTH simultaneously to confirm the diagnosis biochemically 1
• Assess 25-hydroxyvitamin D status, as vitamin D deficiency can complicate PTH interpretation and cause secondary hyperparathyroidism 1
• Note that PTH assays vary significantly between laboratories, so use assay-specific reference values 1

Surgical Management (Primary Treatment)

Parathyroidectomy is indicated for patients with:

• Symptomatic disease including kidney stones, bone pain, fractures, or neuromuscular symptoms 1
• Osteoporosis on DEXA scan 1
• Impaired kidney function (GFR < 60 mL/min/1.73 m²) 1
• Hypercalciuria 1

For patients over 50 years with serum calcium less than 1 mg/dL above the upper normal limit and no evidence of skeletal or kidney disease, observation with monitoring may be appropriate. 2

Preoperative localization:

• Sestamibi (99Tc-Sestamibi) scan has the highest sensitivity for localizing parathyroid adenomas 1
• Minimally invasive parathyroidectomy (MIP) offers shorter operating times, faster recovery, and decreased perioperative costs compared to bilateral neck exploration, but requires confident preoperative localization of a single adenoma and intraoperative PTH monitoring 1

Medical Management (When Surgery Not Feasible)

For patients unable to undergo parathyroidectomy, cinacalcet is FDA-approved for treatment of hypercalcemia in primary hyperparathyroidism. 4

Cinacalcet dosing for primary hyperparathyroidism:

• Starting dose: 30 mg twice daily 4
• Titrate every 2 to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg 3-4 times daily as necessary to normalize serum calcium 4
• Measure serum calcium within 1 week after initiation or dose adjustment 4
• Once maintenance dose established, monitor serum calcium every 2 months 4

In clinical trials, cinacalcet reduced mean serum calcium by 2.3 mg/dL from baseline (12.7 to 10.4 mg/dL) in patients with severe primary hyperparathyroidism who were unable to undergo surgery. 4

Management of Severe Symptomatic Hypercalcemia

For moderate to severe hypercalcemia (total calcium ≥12 mg/dL):

• Initiate aggressive IV crystalloid hydration with normal saline to restore intravascular volume and promote calciuresis 5
• Administer loop diuretics (furosemide) only after adequate volume repletion to enhance calcium excretion 5
• Give IV bisphosphonates (zoledronic acid or pamidronate) as primary therapy 5
• Consider calcitonin as a temporizing measure for rapid calcium reduction while awaiting bisphosphonate effect 5

For acute symptomatic severe hypercalcemia (total calcium ≥14 mg/dL or ionized calcium ≥10 mg/dL):

• Initiate hypertonic 3% saline IV in addition to aggressive hydration 5

Special Considerations in CKD Patients

For secondary hyperparathyroidism in CKD patients on dialysis (not primary hyperparathyroidism):

• Initial medical management includes dietary phosphate restriction, phosphate binders, correction of hypocalcemia with calcium supplementation, and vitamin D sterols (calcitriol, paricalcitol, doxercalciferol) 1
• Cinacalcet may be considered for persistent secondary hyperparathyroidism despite initial therapy, starting at 30 mg once daily and titrating to target iPTH levels of 150-300 pg/mL 1, 4
• Note: Cinacalcet is NOT indicated for CKD patients not on dialysis due to increased risk of hypocalcemia 4

Parathyroidectomy in CKD patients on dialysis is reserved for:

• Refractory and/or symptomatic hypercalcemia (after exclusion of other causes) 6
• Refractory hyperphosphatemia 6
• Severe intractable pruritus 6
• Serum calcium × phosphorus product persistently exceeding 70-80 mg/dL with progressive extraskeletal calcifications 6
• Calciphylaxis 6

Common Pitfalls

Avoid these errors:

• Do not use cinacalcet in CKD patients not on dialysis due to hypocalcemia risk 4
• Do not assume all hypercalcemia with elevated PTH is primary hyperparathyroidism—rule out vitamin D deficiency first, as it can cause secondary hyperparathyroidism 1
• Do not overlook familial hypocalciuric hypercalcemia (FHH) in the differential diagnosis, which presents with hypercalcemia, elevated or inappropriately normal PTH, and hypocalciuria 7
• Avoid calcium-based phosphate binders in patients with hypercalcemia 5