What is the algorithm for hyperparathyroidism workup and management?

Algorithm for Hyperparathyroidism Workup and Management

The workup for hyperparathyroidism should begin with serum calcium and PTH measurements, followed by targeted diagnostic tests to determine the type of hyperparathyroidism, with management tailored to the specific form identified. 1

Initial Diagnostic Workup

• Measure serum calcium (total calcium corrected for albumin) and intact parathyroid hormone (iPTH) simultaneously 1
• Obtain ionized calcium measurement, which is more sensitive than total serum calcium for detecting primary hyperparathyroidism 2
• Assess serum phosphate, chloride, 25-hydroxyvitamin D, and calcium-to-creatinine clearance ratio to aid in differential diagnosis 3
• Consider measuring 24-hour urinary calcium to rule out familial hypocalciuric hypercalcemia 3

Differential Diagnosis

Primary Hyperparathyroidism (PHPT)

• Characterized by hypercalcemia (or normal-high calcium) with inappropriately normal or elevated PTH 3
• Most common cause of hypercalcemia in ambulatory patients (80-90% of cases) 4
• Risk factors include family history of MEN syndromes, history of neck radiation, and postmenopausal state 4

Secondary Hyperparathyroidism

• Elevated PTH due to hypocalcemia, hyperphosphatemia, or vitamin D deficiency 5
• Common in chronic kidney disease, vitamin D deficiency, malabsorption syndromes 5
• Characterized by normal or low serum calcium with elevated PTH 1

Tertiary Hyperparathyroidism

• Autonomous parathyroid function following long-standing secondary hyperparathyroidism 5
• Characterized by hypercalcemia with elevated PTH 1
• Most common in patients with end-stage renal disease 1

Imaging Studies (After Biochemical Confirmation)

• Ultrasound of the neck as first-line localization study 1
• Dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT (parathyroid scan) 1
• The combination of ultrasound and sestamibi scan provides highest sensitivity for localization 1
• MRI or CT scan may be considered if initial imaging is negative 1

Management Algorithm

Primary Hyperparathyroidism

1. Surgical Management (Definitive Treatment)

   • Parathyroidectomy is the only definitive cure for PHPT 1
   • Surgical approaches include:
     • Resection of solitary enlarged gland
     • Total four-gland parathyroidectomy with autotransplantation 1
   • Transcervical thymectomy often performed simultaneously due to risk of supernumerary parathyroid glands 1
   • Intraoperative PTH monitoring recommended to confirm cure 6

2. Medical Management (When Surgery Not Possible)

   • Cinacalcet indicated for hypercalcemia in patients with PHPT who cannot undergo parathyroidectomy 7
   • Monitor for side effects including nausea (30%), muscle spasms (18%), and hypocalcemia 7
   • Ensure adequate vitamin D levels to prevent secondary hyperparathyroidism 1

Secondary Hyperparathyroidism in Chronic Kidney Disease

1. Medical Management

   • Phosphate restriction and phosphate binders 1
   • Correction of vitamin D deficiency 1
   • Active vitamin D analogs (calcitriol or alfacalcidol) 1
   • Cinacalcet for patients on dialysis with persistent elevated PTH despite standard therapy 7

2. Surgical Management

   • Parathyroidectomy recommended for severe hyperparathyroidism (persistent PTH >800 pg/mL) with hypercalcemia/hyperphosphatemia refractory to medical therapy 1
   • Subtotal parathyroidectomy or total parathyroidectomy with autotransplantation are effective surgical approaches 1

Post-Parathyroidectomy Management

• Monitor ionized calcium every 4-6 hours for first 48-72 hours after surgery 1
• If ionized calcium falls below normal (<0.9 mmol/L), initiate calcium gluconate infusion at 1-2 mg elemental calcium/kg/hour 1
• When oral intake is possible, provide calcium carbonate 1-2g three times daily and calcitriol up to 2μg/day 1
• Adjust phosphate binder therapy based on serum phosphorus levels 1

Special Considerations

• For patients with MEN syndromes, screening for PHPT with serum calcium should begin at age 11 for high-risk variants and age 16 for moderate-risk variants 1
• In patients with X-linked hypophosphatemia, secondary hyperparathyroidism should be managed by increasing active vitamin D and/or decreasing phosphate supplements 1
• Calcimimetics (cinacalcet) may be considered for persistent secondary hyperparathyroidism but should be used with caution due to risk of hypocalcemia 1

Common Pitfalls to Avoid

• Relying solely on total serum calcium without measuring ionized calcium may miss cases of normocalcemic hyperparathyroidism 2, 6
• Failing to correct calcium for albumin can lead to misdiagnosis 3
• Not assessing vitamin D status can complicate interpretation of PTH levels 1
• Using different PTH assay generations without considering their varying sensitivity to PTH fragments can affect clinical decisions 1