What is the management approach for a patient with primary hyperparathyroidism?

Management of Primary Hyperparathyroidism

Surgery is the only curative treatment for primary hyperparathyroidism and should be performed in all patients with hypercalcemia and elevated PTH, even when asymptomatic, due to long-term negative effects on bone density, cardiovascular function, and neurocognitive status. 1, 2

Diagnostic Confirmation

Before proceeding with treatment:

• Measure serum calcium and intact PTH simultaneously to confirm the diagnosis biochemically 2
• Assess 25-hydroxyvitamin D levels, as deficiency can complicate PTH interpretation and mimic secondary hyperparathyroidism 3
• Obtain 24-hour urine calcium measurement to exclude familial hypocalciuric hypercalcemia 3
• Perform dual-energy x-ray absorptiometry (DEXA) to assess bone density 3
• Never use imaging to confirm or exclude the diagnosis—diagnosis is biochemical only 2

Surgical Management: The Definitive Approach

Choosing the Surgical Technique

Minimally invasive parathyroidectomy (MIP) is the preferred surgical approach when preoperative imaging confidently localizes a single parathyroid adenoma, which occurs in 80-85% of cases 4, 1, 2. MIP offers:

• Shorter operating times 4, 1
• Faster recovery 4, 1
• Lower perioperative costs 4, 1

Requirements for MIP:

• Confident preoperative localization of a single adenoma 4
• Intraoperative PTH monitoring using a reliable protocol 4, 3

Bilateral neck exploration (BNE) is necessary when:

• Preoperative imaging is discordant or nonlocalizing 4, 1, 2
• Multigland disease is suspected (occurs in 15-20% of cases) 1, 3
• Familial forms of hyperparathyroidism are present 5, 3

Preoperative Imaging Strategy

Imaging is appropriate for preoperative localization but NOT required to establish surgical indication 2. Common modalities include:

• 99Tc-sestamibi scan 6, 2
• Cervical ultrasonography 2, 3
• 4-D parathyroid CT (multiphase CT without and with IV contrast) 6, 2
• MRI 6, 2

Selection should consider surgeon and radiologist preference, regional expertise, and patient characteristics (e.g., suspected multigland disease, hereditary causes, concomitant thyroid disease) 6. Multiple imaging modalities may be used in combination to maximize accuracy through concordant results 6.

Critical caveat: Patients with nonlocalizing imaging remain surgical candidates—do not delay surgery based on imaging alone 3.

Special Surgical Considerations

For reoperative cases (persistent or recurrent hyperparathyroidism):

• Preoperative imaging with 99Tc-sestamibi, ultrasound, CT, or MRI is mandatory 4, 2
• Reoperations have lower cure rates and higher complication rates than first-time surgery 2
• Imaging helps identify postoperative changes that impact subsequent surgery 6

Intraoperative management:

• The possibility of multigland disease should be routinely considered 3
• Ex vivo aspiration of resected tissue may confirm parathyroid tissue intraoperatively 3
• Devascularized normal parathyroid tissue should be autotransplanted 3
• Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy 3

Postoperative monitoring:

• Observe for hematoma 3
• Evaluate for hypocalcemia and symptoms of hypocalcemia 3
• Calcium supplementation may be indicated postoperatively 3
• Follow up to assess for cure, defined as eucalcemia at more than 6 months 3

Medical Management: Only for Surgical Non-Candidates

Medical therapy is reserved exclusively for patients who meet surgical criteria but are unable or unwilling to undergo parathyroidectomy 7, 8. This is NOT first-line treatment.

Cinacalcet (Calcimimetic Agent)

FDA-approved indication: Treatment of hypercalcemia in adult patients with primary hyperparathyroidism for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy 7

Dosing regimen:

• Starting dose: 30 mg orally twice daily 7
• 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 7
• Goal: Normalize serum calcium levels 7
• Must be taken with food or shortly after a meal 7
• Tablets must be swallowed whole, not chewed, crushed, or divided 7

Monitoring requirements:

• Measure serum calcium within 1 week after initiation or dose adjustment 7
• Once maintenance dose established, measure serum calcium every 2 months 7

Clinical efficacy data:

• In a randomized, double-blind, placebo-controlled study of 67 patients with primary hyperparathyroidism who met criteria for parathyroidectomy but were unable to undergo surgery, 75.8% of cinacalcet-treated patients achieved mean corrected total serum calcium ≤10.3 mg/dL compared to 0% with placebo (p<0.001) 7
• 84.8% achieved ≥1 mg/dL decrease from baseline compared to 5.9% with placebo (p<0.001) 7
• Median dose at study completion was 60 mg/day 7

Critical warning: Monitor closely for hypocalcemia, particularly if serum calcium falls below 8.4 mg/dL 7

Other Medical Options (Less Commonly Used)

Bisphosphonates:

• Lower serum and urinary calcium 9
• Primarily address bone loss rather than hypercalcemia 8, 9
• Generally restricted to research settings for primary hyperparathyroidism 9

Denosumab:

• Alternative for bone protection 8
• Does not normalize calcium levels 8

General supportive measures for asymptomatic patients under observation:

• Maintain adequate hydration 9
• Avoid immobilization 9
• Use diuretics only with caution 9
• Moderate dietary calcium intake (500-800 mg/day) 9

Common Pitfalls to Avoid

Do not delay surgery in favor of medical management—surgery is curative and prevents long-term complications of hypercalcemia on bone, cardiovascular, and neurocognitive function 1, 2. Medical therapy is only a temporizing measure for surgical non-candidates.

Do not use imaging to diagnose primary hyperparathyroidism—diagnosis is biochemical (elevated calcium with elevated or inappropriately normal PTH) 2. Imaging is solely for preoperative localization.

Do not avoid surgery in asymptomatic patients—even asymptomatic disease has potential to cause bone loss, kidney stones, and other complications 1, 10. Surgery is more cost-effective than observation or pharmacologic therapy 3.

Do not perform preoperative parathyroid biopsy—this should be avoided 3.

Be aware that PTH assays vary significantly between laboratories—use assay-specific reference values 2.

Do not supplement vitamin D before correcting deficiency—vitamin D deficiency should be treated before surgery as it can complicate interpretation and worsen postoperative hypocalcemia 3.