What is the initial step in a parathyroid (parathyroid gland) workup for a patient with suspected hyperparathyroidism (elevated parathyroid hormone levels)?

Initial Workup for Suspected Hyperparathyroidism

The initial step in a parathyroid workup for suspected hyperparathyroidism is simultaneous measurement of serum calcium and intact parathyroid hormone (iPTH) levels. 1

Diagnostic Algorithm

1. First-line laboratory tests:

   • Serum calcium (preferably ionized calcium if available, otherwise albumin-corrected total calcium)
   • Intact parathyroid hormone (iPTH)
   • 25-OH Vitamin D level (to exclude vitamin D deficiency as a secondary cause)

2. Interpretation of results:

   • Hypercalcemia with normal or elevated iPTH confirms primary hyperparathyroidism
   • Hypercalcemia with suppressed iPTH suggests non-parathyroid causes of hypercalcemia
   • Normal calcium with elevated iPTH suggests secondary hyperparathyroidism (often due to vitamin D deficiency or renal disease)

3. Additional laboratory tests once hyperparathyroidism is suspected:

   • Serum phosphorus (typically low in primary hyperparathyroidism)
   • Serum creatinine and estimated GFR (to assess kidney function)
   • 24-hour urinary calcium excretion (to differentiate familial hypocalciuric hypercalcemia)
   • Alkaline phosphatase (to assess for bone involvement)

Clinical Considerations

• Even with normal PTH levels, primary hyperparathyroidism may still be present if calcium is elevated, as approximately 7% of patients with primary hyperparathyroidism have PTH values within the normal range 2.

• The combination of hypercalcemia and non-suppressed PTH (even if within normal range) is highly suggestive of primary hyperparathyroidism 1, 3.

• Vitamin D deficiency should be identified and corrected, as it can cause secondary elevation of PTH and mask the true calcium levels in primary hyperparathyroidism 1.

Imaging Considerations

Imaging studies should only be performed after biochemical confirmation of hyperparathyroidism, not as part of the initial diagnostic workup. When indicated, options include:

• Ultrasound of the neck
• 99mTc-sestamibi scintigraphy with SPECT/CT (parathyroid scan)
• The combination of these two tests provides high sensitivity for localization of parathyroid adenomas 1

Common Pitfalls to Avoid

1. Relying solely on PTH levels: Some patients with primary hyperparathyroidism may have PTH values within the normal range 2.

2. Failing to check vitamin D status: Vitamin D deficiency can cause secondary hyperparathyroidism and should be excluded 1.

3. Premature imaging: Performing imaging studies before biochemical confirmation wastes resources and may lead to false positives or negatives.

4. Inadequate calcium measurement: Using non-corrected calcium levels in hypoalbuminemic patients can lead to missed diagnoses.

5. Overlooking medications: Certain medications (thiazide diuretics, lithium) can cause or exacerbate hyperparathyroidism.

By following this systematic approach to the initial parathyroid workup, clinicians can accurately diagnose hyperparathyroidism and determine the appropriate next steps for management, ultimately reducing morbidity and mortality associated with untreated disease.