What is the current workup for hyperparathyroidism?

Current Workup for Hyperparathyroidism

The definitive workup for hyperparathyroidism requires simultaneous measurement of serum calcium and intact parathyroid hormone (iPTH) levels as the essential first step, followed by appropriate imaging studies for localization if surgical intervention is indicated. 1

Initial Diagnostic Testing

• Measure serum calcium (total calcium corrected for albumin) and intact parathyroid hormone (iPTH) simultaneously for accurate diagnosis 1
• Assess 25-OH Vitamin D levels to exclude hypovitaminosis D as a concomitant secondary cause of hyperparathyroidism 2
• Measure serum phosphate, chloride, and calcium-to-creatinine clearance ratio to help differentiate between types of hyperparathyroidism 1
• For primary hyperparathyroidism (PHPT), findings typically include hypercalcemia with elevated or inappropriately normal PTH levels 3
• For secondary hyperparathyroidism, findings typically include normal or low serum calcium with elevated PTH, often seen in chronic kidney disease, vitamin D deficiency, and malabsorption syndromes 1

Differential Diagnosis Parameters

• Primary hyperparathyroidism: characterized by autonomous PTH production with hypercalcemia or normal-high calcium levels with elevated or inappropriately normal PTH 4
• Secondary hyperparathyroidism: elevated PTH due to hypocalcemia, hyperphosphatemia, or vitamin D deficiency, commonly seen in chronic kidney disease 5
• Tertiary hyperparathyroidism: hypercalcemia with elevated PTH, typically in patients with end-stage renal disease 1
• Normocalcemic hyperparathyroidism: high PTH levels with persistently normal albumin-corrected and ionized serum calcium values 3

Imaging Studies for Localization

• Ultrasound of the neck is recommended as the first-line localization study for hyperparathyroidism 1
• Dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT (parathyroid scan) should be performed for localizing parathyroid adenomas or hyperplasia 1
• The combination of ultrasound and sestamibi scan provides the highest sensitivity for localization 1
• For negative initial imaging, MRI or CT scan may be considered 1
• Before surgery, imaging with ultrasound and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT is highly sensitive for localizing parathyroid adenomas 2

Special Considerations in the Workup

• In patients with chronic kidney disease (CKD), PTH should be monitored when GFR falls below 60 mL/min/1.73 m² 5
• For CKD patients, target ranges for PTH vary by disease stage, and monitoring frequency should be adjusted based on baseline PTH levels 5
• Be aware that different PTH assay generations can affect clinical decisions - standardization of PTH assays is ongoing, and lack of standardization leads to remarkable differences in PTH concentrations measured in different laboratories 5
• For patients with suspected familial hyperparathyroidism or multiple endocrine neoplasia (MEN) syndromes, genetic testing should be considered 6

Common Pitfalls to Avoid

• Not assessing vitamin D status can complicate the interpretation of PTH levels 1
• Using different PTH assay generations without considering their varying sensitivity to PTH fragments can affect clinical decisions 5
• Relying solely on a single PTH measurement without considering the calcium level can lead to misdiagnosis 1
• Failure to recognize normocalcemic hyperparathyroidism, which requires measurement of PTH in the evaluation of low bone density or osteoporosis 3

Treatment Considerations Following Diagnosis

• Surgical excision of abnormal parathyroid tissue is the only definitive cure for primary hyperparathyroidism 2
• Indications for parathyroidectomy in PHPT include: age ≤50 years, serum calcium >1 mg/dL above upper limit of normal, osteoporosis, creatinine clearance <60 mL/min/1.73 m², nephrolithiasis, nephrocalcinosis, or hypercalciuria 6
• For secondary hyperparathyroidism in CKD, initial treatment includes dietary phosphate restriction, phosphate binders, correction of hypocalcemia, and vitamin D supplementation 2
• Cinacalcet may be considered for persistent secondary hyperparathyroidism but should be used with caution due to the risk of hypocalcemia 7