What are the implications of hyperparathyroidism?

Implications of Hyperparathyroidism (PTH 82)

Hyperparathyroidism has significant implications for morbidity and mortality, primarily affecting bone health, cardiovascular function, and renal function, requiring prompt diagnosis and management to prevent complications.

Types of Hyperparathyroidism

• Primary hyperparathyroidism (PHPT): Characterized by autonomous production of PTH from parathyroid glands, typically due to adenoma or hyperplasia, resulting in hypercalcemia or high-normal calcium with elevated or inappropriately normal PTH levels 1
• Secondary hyperparathyroidism (SHPT): Results from chronic stimulation of parathyroid glands due to low circulating calcium, commonly seen in chronic kidney disease (CKD) or vitamin D deficiency 2
• Tertiary hyperparathyroidism: Develops from long-standing secondary hyperparathyroidism that becomes autonomous once the original cause is removed 2

Clinical Manifestations and Complications

Bone Complications

• Increased bone turnover leading to osteoporosis, osteopenia, and increased fracture risk 3
• Bone pain and pathological fractures in severe cases 1
• Subperiosteal bone resorption, particularly visible in hand radiographs 1
• Renal osteodystrophy in patients with CKD 4

Renal Complications

• Increased risk of nephrolithiasis (kidney stones) and nephrocalcinosis 1
• Reduced renal function, particularly in post-transplant patients with persistent hyperparathyroidism 4
• Hypercalciuria leading to stone formation in primary hyperparathyroidism 1

Cardiovascular Complications

• Vascular calcification due to elevated calcium-phosphate product, particularly in CKD patients 4
• Increased risk of cardiac disease, the leading cause of death in CKD patients 4
• Hypertension may be associated with hyperparathyroidism 4

Neuropsychiatric Manifestations

• Fatigue, depression, and cognitive dysfunction 3
• Psychological disturbances requiring intervention in severe cases 4

Other Complications

• Pruritus (severe itching), particularly in CKD patients 4
• Gastrointestinal symptoms including abdominal pain and constipation 3
• Calciphylaxis (calcific uremic arteriolopathy) in severe cases 4

Diagnostic Evaluation

• Laboratory assessment: Measurement of serum calcium (total and ionized), phosphorus, PTH, vitamin D levels, and alkaline phosphatase 5
• Urinary calcium: Important to exclude familial benign hypocalciuric hypercalcemia 1
• Bone mineral density: DEXA scan to assess bone loss 1
• Imaging: Ultrasound, 99mTc-sestamibi scan, CT, or MRI for localization of parathyroid adenomas prior to surgery 4
• Bone biopsy: May be necessary in CKD patients with PTH levels between 100-500 pg/mL who develop unexplained hypercalcemia, bone pain, or increased bone alkaline phosphatase 4

Management Approaches

Medical Management

• For Primary Hyperparathyroidism:

  • Cinacalcet (calcimimetic) is FDA-approved for hypercalcemia in patients with primary HPT who cannot undergo parathyroidectomy 6
  • Bisphosphonates and hormone replacement therapy may help manage bone disease 3
  • Regular monitoring of calcium, PTH, and bone density in asymptomatic cases 1

• For Secondary Hyperparathyroidism in CKD:

  • Phosphate restriction and phosphate binders to maintain phosphorus between 3.5-5.5 mg/dL 4
  • Vitamin D analogs (calcitriol, paricalcitol) to suppress PTH 2
  • Cinacalcet for patients on dialysis with refractory SHPT 6
  • Avoid cinacalcet in non-dialysis CKD patients due to increased risk of hypocalcemia 6

Surgical Management

• Parathyroidectomy indications for PHPT:

  • Symptomatic patients with osteoporosis, impaired kidney function, kidney stones, or hypercalciuria 4
  • Patients ≥50 years with calcium >0.25 mmol/L above upper limit of normal 4

• Parathyroidectomy indications for SHPT in CKD:

  • Persistent serum levels of intact PTH >800 pg/mL (88.0 pmol/L) 4
  • Associated hypercalcemia and/or hyperphosphatemia refractory to medical therapy 4
  • Calciphylaxis with elevated PTH levels 4

• Surgical approaches:

  • Subtotal parathyroidectomy or total parathyroidectomy with parathyroid tissue autotransplantation 4
  • Minimally invasive approaches for solitary adenomas in primary hyperparathyroidism 7
  • Bone biopsy may be required prior to parathyroidectomy in patients with PTH levels <800-1000 pg/mL to confirm hyperparathyroidism 4

Special Considerations

In Children with CKD

• Growth hormone therapy should be withheld in patients with persistent severe secondary hyperparathyroidism (PTH >500 pg/ml) 4
• Therapy can be reinstituted when PTH levels return to target range 4

In Renal Transplant Recipients

• Persistent hyperparathyroidism occurs in approximately 30% of renal transplant recipients up to 3 years post-transplant 4
• Hypercalcemia is the most common biochemical marker, reported in 10-22% of renal transplant recipients 4
• Parathyroidectomy should be considered for refractory hypercalcemia, hyperphosphatemia, severe pruritus, or high calcium-phosphorus products with extraskeletal calcifications 4

Monitoring Recommendations

• Regular monitoring of calcium, phosphorus, and PTH levels 4
• Assessment of bone mineral density in patients with persistent disease 1
• Monitoring for complications including kidney stones, bone disease, and vascular calcifications 4
• Post-parathyroidectomy monitoring of ionized calcium every 4-6 hours for the first 48-72 hours, then twice daily until stable 4