What is the recommended treatment for a patient with Primary Hyperparathyroidism (PHPT)?

Treatment of Primary Hyperparathyroidism (PHPT)

Parathyroidectomy is the definitive and only curative treatment for PHPT, with minimally invasive parathyroidectomy (MIP) being the preferred approach when a single adenoma is confidently localized preoperatively, while bilateral neck exploration (BNE) remains necessary for cases with nonlocalizing imaging or suspected multigland disease. 1

Surgical Management: The Primary Treatment

Minimally Invasive Parathyroidectomy (MIP)

• MIP is appropriate for approximately 80% of PHPT patients and offers significant advantages including shorter operating times, faster recovery, and decreased perioperative costs compared to BNE 1
• This approach requires two critical prerequisites: confident preoperative localization of a single parathyroid adenoma and availability of intraoperative PTH monitoring to confirm removal of the hyperfunctioning gland 1
• Preoperative imaging with sestamibi scan, ultrasound, or 4D-CT should be performed to guide the surgical approach 2

Bilateral Neck Exploration (BNE)

• BNE is required when preoperative imaging is discordant or nonlocalizing, and when multigland disease is suspected 1
• This approach is particularly important for patients with PTH ≤50 pg/mL, as 58.9% of these patients have multigland disease 2
• BNE remains the gold standard procedure in parathyroid surgery despite the advantages of MIP 1

Surgical Indications

Parathyroidectomy is indicated for:

• All symptomatic PHPT patients (bone pain, pathological fractures, nephrolithiasis, neurocognitive symptoms) 2
• Asymptomatic PHPT patients with evidence of target organ involvement (osteoporosis, vertebral fractures, hypercalciuria) 2
• The procedure is typically indicated even when asymptomatic, given the potential negative effects of long-term hypercalcemia 2

Medical Management: Limited Role

Cinacalcet (Calcimimetic)

Cinacalcet is FDA-approved for PHPT only in the specific circumstance where parathyroidectomy would be indicated based on serum calcium levels, but the patient is unable to undergo surgery 3

Dosing and Administration

• Starting dose: 30 mg orally twice daily, taken with food or shortly after a meal 3
• Titrate every 2 to 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 3
• Serum calcium should be measured within 1 week after initiation or dose adjustment 3

Critical Limitations and Monitoring

• Cinacalcet lowers serum calcium but does not address the underlying parathyroid pathology and cannot improve bone density 3
• Hypocalcemia is a significant risk: in clinical trials, 6.1% of cinacalcet-treated PHPT patients developed serum calcium <8.4 mg/dL 3
• Common adverse effects include nausea (30%), vomiting, muscle spasms (18%), and headache (12%) 3
• Severe or prolonged nausea and vomiting can lead to dehydration and paradoxically worsen hypercalcemia, requiring careful electrolyte monitoring 3
• Once maintenance dose is established, monitor serum calcium every 2 months 3

Important Caveat

Medical therapy with cinacalcet is NOT a substitute for surgery in surgical candidates - it is reserved exclusively for patients who cannot undergo parathyroidectomy 3. No single medical therapy can both increase bone density and reduce serum calcium levels 4.

Clinical Presentation Context

Asymptomatic Disease

• In countries with routine biochemical screening (United States, Canada, most of Europe), up to 80% of PHPT patients present asymptomatically or with mild, nonspecific symptoms 2
• Even asymptomatic patients should be considered for parathyroidectomy given the risk of progressive target organ damage 2

Symptomatic Disease

Target organ manifestations include:

• Skeletal: bone demineralization, osteoporosis, pathological fractures 2
• Renal: nephrolithiasis and nephrocalcinosis 2
• Neuromuscular: muscle weakness 2
• Neuropsychiatric: neurocognitive disorders 2

Common Pitfalls to Avoid

• Do not use cinacalcet as first-line therapy in surgical candidates - it is only for patients unable to undergo surgery 3
• Do not assume negative imaging is a contraindication for surgery - surgical indication is based on biochemical diagnosis and clinical criteria, not imaging results 5
• Do not overlook multigland disease risk factors - patients with PTH ≤50 pg/mL or familial forms require BNE rather than MIP 2
• Do not delay surgery in symptomatic patients - parathyroidectomy results in documented improvement in bone density and reduction in nephrolithiasis 2, 4