What is the treatment for primary hyperparathyroidism?

Treatment of Primary Hyperparathyroidism

Surgery via parathyroidectomy is the only definitive curative treatment for primary hyperparathyroidism and should be performed in most patients, with minimally invasive parathyroidectomy (MIP) as the preferred approach when preoperative imaging confidently localizes a single adenoma. 1, 2

Surgical Management: The Definitive Treatment

First-Line Approach: Parathyroidectomy

• Parathyroidectomy is indicated for symptomatic primary hyperparathyroidism and typically recommended even in asymptomatic cases given the potential negative effects of long-term hypercalcemia on bone, kidney, and neurocognitive function 2
• Surgery achieves cure rates of 95-98% when performed by experienced parathyroid surgeons 1, 3

Choosing the Surgical Technique

Minimally Invasive Parathyroidectomy (MIP):

• MIP is the preferred approach when preoperative imaging (99Tc-Sestamibi scan, ultrasound, CT, or MRI) confidently localizes a single parathyroid adenoma 1
• MIP offers shorter operating times, faster recovery, and decreased perioperative costs compared to bilateral neck exploration 1
• This approach requires intraoperative PTH monitoring to confirm adequate removal of hyperfunctioning tissue 1
• MIP is appropriate for 80-90% of primary hyperparathyroidism patients who have a single adenoma detected on preoperative imaging 3

Bilateral Neck Exploration (BNE):

• BNE remains the gold standard and is necessary when imaging is discordant, nonlocalizing, or suggests multigland disease 1
• BNE is mandatory for familial forms of primary hyperparathyroidism where multigland disease is more likely 1, 4
• Surgeons performing MIP must be prepared to convert to BNE if the intended gland is not found or if intraoperative PTH does not fall appropriately 3

Critical Surgical Principles

• The surgeon must have thorough knowledge of parathyroid anatomy and embryology, including common ectopic locations 3
• Upper parathyroid glands typically locate at the cricothyroid junction on the posterolateral middle-to-upper thyroid, while lower glands are within 1 cm posterior, lateral, or anterolateral to the lower thyroid pole 3
• If the intended gland is not found in its normal anatomical site during MIP, investigate possible embryological and acquired ectopic locations before converting to BNE 3

Medical Management: Limited Role

Calcimimetics (Cinacalcet)

Cinacalcet is indicated ONLY for patients with primary hyperparathyroidism who meet surgical criteria based on serum calcium levels but are unable to undergo parathyroidectomy. 5

Dosing and Administration:

• Starting dose: 30 mg orally twice daily with food 5
• Titrate every 2-4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and up to 90 mg 3-4 times daily to normalize serum calcium 5
• Measure serum calcium within 1 week after initiation or dose adjustment 5
• Once maintenance dose established, monitor serum calcium every 2 months 5

Important Limitations and Risks:

• Cinacalcet does NOT cure primary hyperparathyroidism—it only manages hypercalcemia 5
• Common adverse effects include nausea (30%), vomiting (46%), muscle spasms (18%), and headache (12%) 5
• Hypocalcemia is a significant risk, occurring in 6.1% of treated patients in clinical trials 5
• Severe nausea and vomiting can lead to dehydration and paradoxically worsen hypercalcemia, requiring careful electrolyte monitoring 5

Other Medical Therapies

• Bisphosphonates, estrogens, and selective estrogen receptor modulators may provide symptomatic control of bone manifestations but do not address the underlying disease 6
• These agents are not curative and should only be considered when surgery is absolutely contraindicated 6

Clinical Presentation Guides Urgency

Asymptomatic Disease (Most Common in Screening Countries)

• Up to 80% of patients in countries with routine biochemical screening present asymptomatically 2
• Surgery is still typically indicated due to long-term risks of hypercalcemia on target organs 2

Symptomatic Disease Requiring Prompt Surgery

• Skeletal manifestations: Bone pain, osteoporosis, pathological fractures, elevated alkaline phosphatase 2
• Renal manifestations: Nephrolithiasis, nephrocalcinosis, progressive renal damage 2
• Neuromuscular manifestations: Muscle weakness 2
• Neuropsychiatric manifestations: Neurocognitive disorders, psychological disturbances 2
• Symptomatic patients experience documented resolution of bone pain and improvement in bone density after parathyroidectomy 2

Common Pitfalls to Avoid

• Do not use cinacalcet as first-line therapy when surgery is feasible—it is only for patients unable to undergo parathyroidectomy 5
• Do not perform MIP without confident preoperative localization—this leads to higher failure rates and need for conversion to BNE 1
• Do not skip intraoperative PTH monitoring during MIP—this is essential to confirm adequate resection 1
• Do not assume negative imaging is a contraindication to surgery—BNE can still be performed successfully 7
• Ensure vitamin D status is optimized before finalizing diagnosis, as vitamin D deficiency can cause secondary hyperparathyroidism that mimics primary disease 8