What are the treatment options for primary hyperparathyroidism?

Treatment Options for Primary Hyperparathyroidism

Definitive Treatment: Surgery

Parathyroidectomy is the only curative treatment for primary hyperparathyroidism and should be performed in all symptomatic patients and most asymptomatic patients, as it is more cost-effective than observation or pharmacologic therapy. 1, 2, 3

Surgical Approach Selection

Two effective surgical techniques exist, and the choice depends on preoperative imaging results:

Minimally Invasive Parathyroidectomy (MIP)

• MIP is the preferred approach when preoperative imaging confidently localizes a single parathyroid adenoma 1
• Offers shorter operating times, faster recovery, and decreased perioperative costs compared to bilateral neck exploration 1
• Requires intraoperative PTH monitoring using a reliable protocol: blood samples drawn from peripheral veins with postresection PTH levels measured 10-15 minutes after gland removal, demonstrating >50% decrease from baseline AND falling into the normal range 1, 4
• Successfully identifies pathological glands in 70-80% of patients with single adenomas using sestamibi nuclear scan and neck ultrasound 4
• Achieves cure rates exceeding 95% in experienced centers 3, 5

Bilateral Neck Exploration (BNE)

• BNE remains necessary for cases with discordant/nonlocalizing imaging or suspected multigland disease 1
• Remains the gold standard procedure in parathyroid surgery despite MIP being standard for selected patients 6
• Essential because 10-30% of patients have multigland disease (double adenomas or hyperplasia), and preoperative imaging sensitivity for detecting all abnormal glands in multigland disease is extremely low 4

Critical Surgical Considerations

Surgeons must be proficient in both MIP and BNE techniques, as these are complementary rather than alternative approaches 6:

• The surgeon must be prepared to convert from MIP to BNE if the intended gland is not found or if intraoperative findings suggest multigland disease 6
• High-volume surgeons achieve better outcomes 3
• The possibility of multigland disease should be routinely considered in all cases 3

Preoperative Evaluation Requirements

Before surgery, complete the following workup 3:

• Measure 25-hydroxyvitamin D levels and supplement if deficient 3
• Obtain 24-hour urine calcium measurement 3
• Perform dual-energy x-ray absorptiometry (bone density scan) 3
• Obtain cervical ultrasonography or other high-resolution imaging for operative planning 3
• Patients with nonlocalizing imaging remain surgical candidates 3
• Avoid preoperative parathyroid biopsy 3

Postoperative Management

Monitor patients carefully after surgery 3:

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

Medical Management: Limited Role

Cinacalcet (Calcimimetic)

Cinacalcet is FDA-approved only for hypercalcemia in adult patients with primary hyperparathyroidism who meet criteria for parathyroidectomy based on serum calcium levels but are unable to undergo surgery 7:

Dosing and Administration

• Starting dose: 30 mg orally twice daily 7
• Titrate every 2-4 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 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 approximately every 2 months 7

Significant Adverse Effects

• Nausea (63% of patients), vomiting (46%), and paresthesia (20%) are common 7
• Severe or prolonged nausea and vomiting can lead to dehydration and worsening hypercalcemia, requiring careful electrolyte monitoring 7
• Hypocalcemia occurred in 6.1% of cinacalcet-treated patients versus 0% of placebo patients in primary hyperparathyroidism studies 7

Important Limitation

Cinacalcet is NOT a substitute for surgery and should only be used when parathyroidectomy is contraindicated or the patient refuses surgery 7. Surgery remains superior for morbidity, mortality, and quality of life outcomes.

Special Circumstances

Reoperative Parathyroidectomy

• Perform preoperative imaging with 99Tc-Sestamibi scan, ultrasound, CT scan, or MRI to localize target parathyroid lesions and identify postoperative changes 1
• Consider 4D-CT or 4D-MRI as secondary imaging when conventional methods fail to localize the lesion 5
• PET/CT with 11C-choline or 18F-fluorocholine shows promise as an emerging imaging modality 5
• Persistent hyperparathyroidism (hypercalcemia within 6 months) occurs in 2-22% of cases, while recurrent disease (after >6 months normocalcemia) occurs in 1-15% 5

Familial Primary Hyperparathyroidism and Parathyroid Carcinoma

• These challenging entities require special consideration and surgical expertise 3