What are the treatment options for managing pain in patients with hyperparathyroidism?

Pain Management in Hyperparathyroidism

Parathyroidectomy is the definitive treatment for bone pain due to hyperparathyroidism, especially in cases with severe hyperparathyroidism (PTH >800 pg/mL) that is refractory to medical therapy, with a 95-98% cure rate when performed by an experienced surgeon. 1

Types of Hyperparathyroidism and Pain Presentation

Hyperparathyroidism can present as:

• Primary hyperparathyroidism (PHPT): Due to intrinsic abnormal changes in the parathyroid glands
• Secondary hyperparathyroidism: Due to extrinsic factors affecting calcium homeostasis (often in CKD)
• Tertiary hyperparathyroidism: Persistent hyperparathyroidism after longstanding secondary hyperparathyroidism

Pain in hyperparathyroidism commonly manifests as:

• Bone pain (most common)
• Musculoskeletal symptoms
• Pain from pathological fractures
• Pain from renal stones

Treatment Algorithm for Pain in Hyperparathyroidism

First-Line: Definitive Treatment

1. Surgical Management:
   • Parathyroidectomy for severe hyperparathyroidism (PTH >800 pg/mL) 1
   • Minimally invasive parathyroidectomy (MIP) if preoperative imaging localizes a single adenoma
   • Bilateral neck exploration (BNE) if imaging is discordant or non-localizing

Second-Line: Medical Management

For patients who cannot undergo surgery or while awaiting surgery:

1. Vitamin D Supplementation:

   • Correct vitamin D deficiency with high-dose cholecalciferol (50,000 IU weekly for 8-12 weeks) 1
   • For hypocalcemia (<8.5 mg/dl), add elemental calcium 1 g/day

2. Active Vitamin D Analogs:

   • Calcitriol to reverse high-turnover bone disease and alleviate musculoskeletal symptoms 2
   • Dosage adjusted based on severity of hyperparathyroidism

3. Calcimimetics:

   • Cinacalcet for patients with primary hyperparathyroidism who cannot undergo surgery 3
   • Starting dose: 30 mg twice daily, titrated every 2-4 weeks as needed
   • Monitor serum calcium levels closely

4. Bisphosphonates and Denosumab:

   • Effective for mitigating bone loss and hypercalcemia 4
   • Alendronate significantly increases BMD at lumbar spine and decreases bone turnover markers 5
   • Consider for elderly patients with osteoporosis and mild PHPT who are unsuitable for surgery

For Bone Metastases in Thyroid Cancer with Hyperparathyroidism

1. Bone Resorption Inhibitors:

   • Bisphosphonates or denosumab every 4 weeks or 3 months 2
   • Maintain adequate calcium and vitamin D levels during treatment
   • Dental evaluation before starting treatment due to risk of jaw osteonecrosis

2. Radiation Therapy:

   • External beam radiotherapy (EBRT): 20 Gy in five fractions or 30 Gy in 10 fractions
   • Single-fraction (8 Gy) for palliative treatment
   • Pain relief often achieved within 48-72 hours, though may take up to 1 month

3. Interventional Techniques:

   • Cementoplasty for vertebral body fractures
   • Radiofrequency ablation (RFA) for localized lesions
   • Percutaneous vertebroplasty for vertebral pain and deformity

Monitoring During Treatment

• Monitor serum calcium, phosphorus, and iPTH every 3 months for patients with GFR < 30 ml/min/1.73m² 1
• Check calcium levels every 4-6 hours for the first 48-72 hours after parathyroidectomy
• For patients on cinacalcet, monitor serum calcium approximately monthly for secondary hyperparathyroidism and every 2 months for primary hyperparathyroidism 3

Special Considerations

• If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL during treatment, increase calcium-containing phosphate binders and/or vitamin D sterols 3
• If serum calcium falls below 7.5 mg/dL, withhold cinacalcet until levels reach 8 mg/dL, then restart at a lower dose 1
• For pregnant women with hyperparathyroidism pain, consider active vitamin D in combination with phosphate supplements 1

Pitfalls to Avoid

• Avoid cinacalcet in patients with CKD who are not on dialysis due to increased risk of hypocalcemia 3
• Don't overlook vitamin D deficiency, which can exacerbate secondary hyperparathyroidism
• Be cautious with bone resorption inhibitors in patients receiving antiangiogenic therapy due to increased risk of jaw osteonecrosis 2
• Monitor for hypercalcemia when using vitamin D analogs, as this is a major side effect 2

By following this structured approach to pain management in hyperparathyroidism, clinicians can effectively address both the symptoms and underlying causes of pain in these patients.