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

Management of Primary Hyperparathyroidism

Parathyroidectomy is the only curative treatment for primary hyperparathyroidism and should be performed in all patients who meet surgical criteria, including those with symptomatic disease (kidney stones, bone pain, fractures, neuromuscular symptoms), osteoporosis on DEXA scan, hypercalciuria, or impaired kidney function (GFR < 60 mL/min/1.73 m²). 1, 2

Initial Diagnostic Confirmation

Before proceeding with treatment decisions, confirm the diagnosis biochemically:

• Measure serum calcium (corrected for albumin) and intact PTH simultaneously - the hallmark is elevated or inappropriately "normal" PTH in the setting of hypercalcemia 1, 2
• Assess vitamin D status - vitamin D deficiency can cause secondary hyperparathyroidism and must be ruled out before attributing elevated PTH to primary disease 1, 2
• Use assay-specific reference values - PTH assays vary significantly between laboratories and different generations have variable sensitivity to PTH fragments 1, 2

Surgical Management: The Definitive Approach

Patient Selection for Surgery

Surgery is indicated for 1, 2:

• Symptomatic patients: kidney stones, nephrocalcinosis, bone pain, pathological fractures, muscle weakness, neurocognitive disorders
• Asymptomatic patients with: osteoporosis, GFR < 60 mL/min/1.73 m², age < 50 years, serum calcium > 1 mg/dL above upper limit of normal, hypercalciuria
• Even asymptomatic disease typically warrants surgery given the potential negative effects of long-term hypercalcemia including progressive vascular calcification 1

Surgical Technique Selection

Minimally invasive parathyroidectomy (MIP) is the preferred approach when a single parathyroid adenoma is confidently localized preoperatively, offering shorter operating times, faster recovery, and decreased perioperative costs compared to bilateral neck exploration. 3, 2

MIP requires two critical elements 3:

• Confident preoperative localization of a single parathyroid adenoma
• Intraoperative PTH monitoring to confirm adequate resection

Bilateral neck exploration (BNE) remains necessary for 3, 4:

• Discordant or nonlocalizing imaging results
• Suspected multigland disease
• Familial forms of primary hyperparathyroidism
• Failed MIP procedures

Preoperative Imaging Strategy

Multiple imaging modalities should be utilized in combination to maximize accuracy and confidence of parathyroid localization via concordant results 5:

• 99Tc-Sestamibi scan - highest sensitivity for localizing parathyroid adenomas 2
• 4-D parathyroid CT (CT neck without and with IV contrast) - leverages unique perfusion characteristics of parathyroid adenomas 5
• Ultrasound - complementary modality, particularly useful for concurrent thyroid disease evaluation 5

The selection should consider surgeon and radiologist preference, regional expertise, and patient-specific characteristics (suspicion for multigland disease, hereditary causes, concomitant thyroid disease) 5.

Medical Management: Limited Role

Medical therapy is only appropriate for patients who meet surgical criteria but are unable or unwilling to undergo parathyroidectomy 6.

Cinacalcet (Calcimimetic)

Cinacalcet is FDA-approved for 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 7:

• Start at 30 mg twice daily 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
• Target: normalize serum calcium levels
• Monitor serum calcium within 1 week after initiation or dose adjustment

Important monitoring 7:

• Once maintenance dose established, measure serum calcium every 2 months
• Watch for hypocalcemia and increased QT interval 3, 2

Adjunctive Therapies

For patients on medical management only 6, 8:

• Bisphosphonates - address bone demineralization and osteoporosis
• Denosumab - alternative antiresorptive agent
• These agents treat skeletal manifestations but do not address the underlying hypercalcemia

Critical Pitfalls to Avoid

• Do not assume normal total calcium rules out hyperparathyroidism - check ionized calcium and PTH levels, as compensatory mechanisms can initially maintain normal total calcium 1
• Do not overlook vitamin D deficiency as a cause of elevated PTH before diagnosing primary hyperparathyroidism 1
• Do not use cinacalcet as first-line therapy when surgery is feasible - it is only for patients unable to undergo parathyroidectomy 7
• Do not perform MIP without confident preoperative localization - be prepared to convert to BNE if the intended gland is not found 4
• PTH levels alone do not determine symptom severity - calcium levels and duration of disease are equally important 1

Postoperative Management

Monitor ionized calcium every 4-6 hours for the first 48-72 hours after surgery, then twice daily until stable 3:

• Initiate calcium gluconate infusion if hypocalcemia develops
• Adjust phosphate binders based on serum phosphorus levels
• Watch for hungry bone syndrome in patients with severe preoperative bone disease