What is the treatment for primary hyperparathyroidism?

Treatment of Primary Hyperparathyroidism

Surgery is the only curative treatment for primary hyperparathyroidism, and parathyroidectomy should be performed in all symptomatic patients and considered for most asymptomatic patients. 1, 2

Surgical Indications

Parathyroidectomy is indicated for:

• All symptomatic patients with primary hyperparathyroidism 1, 3
• Most asymptomatic patients, as surgery is more cost-effective than observation or pharmacologic therapy 4
• Patients with hypercalcemia and elevated PTH levels 2

The American College of Radiology emphasizes that even asymptomatic patients typically warrant surgery given the potential negative effects of long-term hypercalcemia. 3

Surgical Approach Selection

Minimally Invasive Parathyroidectomy (MIP)

MIP is the preferred approach when preoperative imaging confidently localizes a single parathyroid adenoma, which accounts for 80-85% of primary hyperparathyroidism cases. 1, 2

Key requirements for MIP: 1

• Confident preoperative localization of a single adenoma
• Intraoperative PTH monitoring to confirm removal of the hyperfunctioning gland
• Appropriate for approximately 80% of patients

Advantages of MIP over bilateral neck exploration: 1, 2

• Shorter operating times
• Faster recovery
• Decreased perioperative costs

Bilateral Neck Exploration (BNE)

BNE is required when: 1, 2

• Preoperative imaging is discordant or nonlocalizing
• Multigland disease is suspected
• PTH levels ≤50 pg/mL (58.9% have multigland disease) 3

BNE remains the gold standard procedure in parathyroid surgery, and surgeons must be prepared to convert from MIP to BNE if the intended gland is not found. 5

Preoperative Evaluation

Essential Biochemical Testing

Diagnosis requires: 3

• Elevated or high-normal intact PTH levels
• Elevated total or ionized calcium levels measured simultaneously

Additional preoperative workup should include: 4

• 25-hydroxyvitamin D measurement (vitamin D deficiency can complicate PTH interpretation) 2
• 24-hour urine calcium measurement 4
• Dual-energy x-ray absorptiometry 4
• Supplementation for vitamin D deficiency 4

Preoperative Imaging

Imaging is essential for operative planning but NOT for diagnosis. 3, 2 The American College of Radiology explicitly advises against using imaging to confirm or exclude the diagnosis of primary hyperparathyroidism, as diagnosis is biochemical only. 2

Common imaging modalities include: 1, 2

• 99Tc-sestamibi scan
• Ultrasound
• 4D-CT
• MRI

Critical caveat: Patients with nonlocalizing imaging remain surgical candidates and should undergo bilateral neck exploration. 4 Preoperative parathyroid biopsy should be avoided. 4

Medical Management (Limited Role)

Cinacalcet for Non-Surgical Candidates

Cinacalcet is indicated only for patients with primary hyperparathyroidism who meet criteria for parathyroidectomy based on serum calcium levels but are unable to undergo surgery. 6

Dosing for primary hyperparathyroidism: 6

• Starting dose: 30 mg twice daily orally with food
• Titrate every 2-4 weeks through sequential doses: 30 mg twice daily → 60 mg twice daily → 90 mg twice daily → 90 mg 3-4 times daily
• Goal: normalize serum calcium levels
• Monitor serum calcium within 1 week after initiation or dose adjustment

Important limitations and adverse effects: 6

• Most common adverse reactions: nausea (30%), vomiting (46%), muscle spasms (18%), headache (12%) 6
• Risk of hypocalcemia (serum calcium <8.4 mg/dL occurred in 6.1% of patients) 6
• Severe nausea and vomiting can lead to dehydration and worsening hypercalcemia 6
• Not a substitute for surgery in surgical candidates

Reoperative Cases

For persistent or recurrent hyperparathyroidism, preoperative imaging is mandatory prior to re-exploration. 2 Reoperations have lower cure rates and higher complication rates than first-time surgery, making precise localization critical. 2

Recommended imaging modalities for reoperative cases: 1

• 99Tc-Sestamibi scan
• Ultrasound
• CT scan
• MRI

Surgeon Experience

Surgeons who perform a high volume of parathyroid operations have better outcomes. 4 The possibility of multigland disease should be routinely considered, and surgeons must be proficient in both MIP and BNE techniques. 4, 5

Postoperative Management

Patients should be: 4

• Observed postoperatively for hematoma
• Evaluated for hypocalcemia and symptoms of hypocalcemia
• Followed up to assess for cure (defined as eucalcemia at >6 months)
• Provided calcium supplementation as indicated

For patients with devascularized normal parathyroid tissue, autotransplantation should be performed. 4

Common Pitfalls to Avoid

• Never use imaging to diagnose primary hyperparathyroidism - diagnosis is biochemical only 2
• Do not perform preoperative parathyroid biopsy 4
• Do not assume nonlocalizing imaging excludes surgical candidacy - these patients should undergo BNE 4
• Be aware that PTH assays vary significantly between laboratories - use assay-specific reference values 2
• Consider ectopic locations (including mediastinum) if the gland is not found in its normal anatomical site 5, 7