What are the recommended tests for diagnosing hyperparathyroidism?

Recommended Tests for Diagnosing Hyperparathyroidism

The diagnosis of hyperparathyroidism requires measurement of serum calcium (preferably ionized calcium) and intact parathyroid hormone (iPTH), with additional tests including 25-OH Vitamin D levels to exclude secondary causes. 1

Primary Diagnostic Tests

• Serum calcium measurement:

  • Total serum calcium (if normo-albuminemic) 1
  • Ionized calcium (preferred) - more sensitive marker of disease and better correlated with PTH levels and adenoma size 2

• Intact parathyroid hormone (iPTH):

  • Must be measured simultaneously with calcium 1
  • Hypercalcemia with normal or elevated iPTH is diagnostic of hyperparathyroidism 1

• 25-OH Vitamin D levels:

  • Essential to exclude vitamin D deficiency as a secondary cause of elevated PTH 1, 3
  • Target level should be >30 ng/mL (75 nmol/L) 3

Additional Tests to Consider

• Phosphate levels:

  • Often low in primary hyperparathyroidism 4
  • Helps differentiate from other causes of hypercalcemia

• Urinary calcium excretion:

  • 24-hour urine calcium
  • Helps differentiate primary hyperparathyroidism (typically normal/high urinary calcium) from familial hypocalciuric hypercalcemia (low urinary calcium) 5

• Serum chloride:

  • Can be helpful in differentiating primary hyperparathyroidism from other causes of hypercalcemia 4

• Renal function tests:

  • eGFR measurement to exclude renal insufficiency as a cause of secondary hyperparathyroidism 5

Imaging (After Biochemical Diagnosis)

• Ultrasound of the neck 1
• 99mTc-sestamibi scintigraphy with SPECT/CT (parathyroid scan) 1
  • These are typically used for localization after biochemical diagnosis, not for initial diagnosis

Important Diagnostic Considerations

• Pitfall #1: Relying solely on total serum calcium can miss cases of normocalcemic hyperparathyroidism. Studies show that ionized calcium is elevated in 95% of cases with normal total calcium levels 6.

• Pitfall #2: Not all hyperparathyroidism presents with elevated PTH. Rare cases may have PTH in the normal range but inappropriately high for the degree of hypercalcemia 7.

• Pitfall #3: Different PTH assay generations measure different fragments and can yield varying results. This is particularly important when following clinical guidelines that recommend specific cutoff values 1.

• Pitfall #4: Always exclude factors that can disturb phospho-calcium parameters before confirming diagnosis 5:

  • Vitamin D deficiency
  • Renal insufficiency
  • Malabsorption
  • Insufficient calcium intake
  • Medications (diuretics, lithium, etc.)

Diagnostic Algorithm

1. Initial screening: Serum calcium (preferably ionized) and iPTH
2. If hypercalcemia with elevated/inappropriately normal iPTH: Proceed to additional tests
3. If normocalcemia with elevated iPTH: Check ionized calcium and exclude secondary causes
4. Exclude secondary causes: 25-OH Vitamin D, renal function, urinary calcium
5. Confirm diagnosis: Repeat testing if needed
6. Localization studies: Only after biochemical diagnosis is confirmed

The combination of elevated serum calcium (especially ionized calcium) and inappropriately normal or elevated PTH levels provides the most accurate diagnosis of primary hyperparathyroidism, with a diagnostic accuracy approaching 99% when used together 4.