When should a patient with primary hyperparathyroidism be referred for parathyroidectomy?

Proper Parathyroidectomy Referral in Primary Hyperparathyroidism

Refer all symptomatic patients with primary hyperparathyroidism for parathyroidectomy immediately, and refer asymptomatic patients who meet any of the following criteria: age <50 years, serum calcium >0.25 mmol/L (>1 mg/dL) above upper limit of normal, GFR <60 mL/min/1.73 m², osteoporosis (T-score ≤-2.5), kidney stones, nephrocalcinosis, or hypercalciuria >400 mg/day. 1, 2

Symptomatic Disease - Immediate Referral

Symptomatic primary hyperparathyroidism always warrants surgical referral. 1, 3, 2 Specific symptoms requiring referral include:

• Skeletal manifestations: Bone pain, pathological fractures, or osteitis fibrosa cystica 3
• Renal manifestations: Nephrolithiasis (kidney stones) or nephrocalcinosis 1, 3, 2
• Neuromuscular symptoms: Muscle weakness 3, 2
• Neuropsychiatric symptoms: Neurocognitive disorders, depression, or anxiety 1, 3, 2
• Gastrointestinal symptoms: Though less specific, these may indicate severe hypercalcemia 4

Asymptomatic Disease - Selective Referral Based on Criteria

Most patients in developed countries with routine biochemical screening present asymptomatically (up to 80%). 3 However, asymptomatic does not mean benign—these patients still require evaluation for surgery based on objective criteria. 2, 5

Absolute Indications for Surgery in Asymptomatic Patients:

• Age <50 years - younger patients have longer exposure to potential complications 2, 5
• Serum calcium >0.25 mmol/L (>1 mg/dL) above upper limit of normal - significant hypercalcemia even without symptoms 2
• Impaired kidney function (GFR <60 mL/min/1.73 m²) - increased risk of progressive renal damage 1, 2
• Osteoporosis (T-score ≤-2.5 at any site) - documented skeletal involvement 2, 5
• Kidney stones or nephrocalcinosis - definite target organ damage 1, 2
• Hypercalciuria >400 mg/day - increased risk of stone formation 2

Urgent Referral Situations

Certain presentations require urgent surgical consultation, not routine referral:

• Hypercalcemic crisis (typically calcium >14 mg/dL with altered mental status) 2
• Calciphylaxis with elevated PTH - surgical intervention may improve outcomes 6, 1, 2
• Severe symptomatic hypercalcemia unresponsive to medical management 2
• Acute kidney injury attributed to hypercalcemia 2

Preoperative Workup Before Referral

Before referring to surgery, ensure the following are completed to facilitate surgical planning:

• Biochemical confirmation: Serum calcium (total and ionized), intact PTH, phosphorus, creatinine/GFR 1
• Vitamin D status: 25-hydroxyvitamin D level (correct deficiency before surgery) 7
• 24-hour urine calcium: To assess hypercalciuria 7
• Bone density (DEXA scan): To evaluate for osteoporosis 7
• Renal imaging if indicated: To assess for nephrolithiasis or nephrocalcinosis 1

Common Pitfalls to Avoid

Do not delay referral for "observation" in patients meeting surgical criteria. While medical surveillance is an option for those not meeting criteria, patients who qualify for surgery should be referred promptly, as observational studies show progression occurs in many patients and cardiovascular risks may be present even in asymptomatic disease. 8, 9

Do not order preoperative parathyroid biopsy - this should be avoided as it can cause complications and is unnecessary. 2, 7

Do not assume normal calcium rules out hyperparathyroidism - normocalcemic hyperparathyroidism exists but represents a distinct entity with lower progression risk and different management. 8

Do not withhold referral based on patient age alone - while age <50 is an absolute indication, older patients meeting other criteria also benefit from surgery. 2, 7

Patients Who May Be Observed Without Surgery

Medical surveillance rather than immediate surgery may be appropriate for asymptomatic patients who meet none of the above criteria and have:

• Age ≥50 years
• Serum calcium <0.25 mmol/L above upper limit of normal
• Normal kidney function (GFR ≥60 mL/min/1.73 m²)
• No osteoporosis (T-score >-2.5)
• No kidney stones or nephrocalcinosis
• Normal or mildly elevated urinary calcium (<400 mg/day)

These patients require close monitoring with annual serum calcium, creatinine, and DEXA scanning every 1-2 years, as approximately 25-30% will progress to meet surgical criteria over time. 5, 8