What is the treatment approach for hyperparathyroidism?

Treatment Approach for Hyperparathyroidism

The treatment of hyperparathyroidism depends fundamentally on whether it is primary, secondary, or tertiary disease, with surgery being the only curative option for primary hyperparathyroidism and medical management being first-line for secondary hyperparathyroidism. 1, 2

Primary Hyperparathyroidism (PHPT)

Surgical Management

Parathyroidectomy is the only curative treatment and should be performed in patients meeting specific surgical criteria. 2, 3

Indications for surgery include: 2, 4

• Age younger than 50 years
• Serum calcium >1 mg/dL above upper limit of normal
• Glomerular filtration rate <60 mL/min/1.73 m²
• Osteoporosis on DEXA scan
• Nephrolithiasis or nephrocalcinosis
• Hypercalciuria
• Symptomatic disease (bone pain, fractures, neuromuscular symptoms)

Surgical approach options: 1

• Minimally invasive parathyroidectomy (MIP) is preferred when confident preoperative localization of a single adenoma is achieved, offering shorter operating times, faster recovery, and decreased perioperative costs 5, 1
• MIP requires intraoperative PTH monitoring to confirm removal of the hyperfunctioning gland 5, 1
• Bilateral neck exploration (BNE) remains necessary for cases with discordant or nonlocalizing preoperative imaging or when multigland disease is suspected 5, 1

Medical Management for Non-Surgical Candidates

For patients who do not meet surgical criteria or cannot undergo surgery: 2, 6

• Optimize calcium and vitamin D intake 6
• Consider antiresorptive therapy for skeletal protection in patients with increased fracture risk 6
• Cinacalcet (calcimimetic agent) starting at 30 mg twice daily, titrated every 2-4 weeks through sequential doses up to 90 mg 3-4 times daily to normalize serum calcium 7
• Monitor serum calcium within 1 week after initiation or dose adjustment 7

Monitoring for Asymptomatic Disease

For patients >50 years with serum calcium <1 mg above upper normal limit and no skeletal or kidney disease, observation is appropriate with: 3, 8

• Biannual serum calcium measurements 8
• Annual urinary calcium excretion measurements 8
• Annual bone mineral density measurements 8

Secondary Hyperparathyroidism (SHPT)

Medical Management (First-Line)

Initial treatment consists of: 1, 2

• Dietary phosphate restriction 1
• Phosphate binders 1
• Correction of hypocalcemia with calcium supplementation 1
• Vitamin D sterols (calcitriol, paricalcitol, doxercalciferol) with dosage adjusted according to severity of hyperparathyroidism 1, 2

For peritoneal dialysis patients specifically: 1

• Oral calcitriol 0.5-1.0 μg or doxercalciferol 2.5-5.0 μg given 2-3 times weekly 1

Monitoring During Medical Treatment

Strict monitoring is essential: 1, 2

• Serum calcium and phosphorus every 2 weeks for 1 month after initiation or dose increase, then monthly 1
• PTH monthly for at least 3 months, then every 3 months once target levels achieved 1

Calcimimetics for Persistent Disease

For persistent secondary hyperparathyroidism despite initial therapy: 1, 2, 7

• Cinacalcet starting at 30 mg once daily, titrated no more frequently than every 2-4 weeks to target iPTH levels of 150-300 pg/mL 1, 7
• Caution: Risk of hypocalcemia and increased QT interval 1, 2
• Serum calcium and phosphorus should be measured within 1 week after initiation or dose adjustment 7
• Not indicated for CKD patients not on dialysis due to increased hypocalcemia risk 7

Surgical Management for Refractory Cases

Parathyroidectomy is recommended for: 5, 1

• Severe hyperparathyroidism with persistent serum intact PTH >800 pg/mL 1
• Associated with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 1

Surgical options include: 5, 1

• Subtotal parathyroidectomy 5, 1
• Total parathyroidectomy with parathyroid tissue autotransplantation 5, 1
• Total parathyroidectomy 5, 1

Important caveat: Total parathyroidectomy is not recommended for patients who may subsequently receive a kidney transplant, as control of serum calcium levels may be problematic post-transplant 1

Tertiary Hyperparathyroidism (THPT)

Surgical excision is recommended for medically refractory cases. 5 THPT occurs in patients with long-standing SHPT, most commonly following kidney transplantation, characterized by lack of PTH suppression despite rising serum calcium levels 5

Postoperative Management

After parathyroidectomy: 1

• Monitor ionized calcium every 4-6 hours for the first 48-72 hours 1
• Then monitor twice daily until stable 1
• Initiate calcium gluconate infusion as needed 1
• Adjust phosphate binders based on serum phosphorus levels 1

Reoperative Cases

Preoperative imaging is essential before reoperative parathyroid surgery: 5, 1

• Use 99Tc-Sestamibi scan, ultrasound, CT scan, or MRI to localize target parathyroid lesions and identify postoperative changes 1
• Parathyroid reoperations have lower cure rates and higher complication rates than first-time surgery 5

Critical Diagnostic Considerations Before Treatment

Before initiating any treatment: 2

• Confirm diagnosis biochemically by measuring serum calcium (corrected for albumin) and intact PTH simultaneously 2
• Assess vitamin D status, as deficiency can complicate PTH interpretation and cause secondary hyperparathyroidism 2, 9
• Correct vitamin D deficiency to achieve 25-OH vitamin D levels >20 ng/mL before making treatment decisions 9
• Ensure adequate dietary calcium intake according to age-related recommendations 9

Important pitfall: PTH assays vary significantly between laboratories and different assay generations have variable sensitivity to PTH fragments, so always use assay-specific reference values when interpreting results 2