What is the appropriate workup for a patient with suspected hyperparathyroidism?

Hyperparathyroidism Workup

Initial Laboratory Evaluation

The workup for suspected hyperparathyroidism requires simultaneous measurement of serum calcium and intact parathyroid hormone (PTH) as the critical first step to differentiate PTH-dependent from PTH-independent causes of hypercalcemia. 1

Essential First-Line Tests

• Serum calcium (total and ionized if available): Elevated or high-normal calcium with elevated PTH confirms primary hyperparathyroidism, while low or low-normal calcium with elevated PTH suggests secondary hyperparathyroidism 1
• Intact PTH (iPTH): This distinguishes primary hyperparathyroidism from other causes of hypercalcemia; inappropriately normal or elevated PTH in the setting of hypercalcemia is diagnostic 1
• Serum phosphorus: Typically low in primary hyperparathyroidism, helping differentiate from other causes 1
• Serum creatinine and eGFR: Essential to distinguish primary from secondary hyperparathyroidism related to chronic kidney disease 1
• 25-hydroxyvitamin D: Must be measured as vitamin D deficiency can mask the severity of hyperparathyroidism and is a reversible cause of secondary hyperparathyroidism; target level ≥20 ng/mL (50 nmol/L) 1, 2
• Serum albumin: Needed to correct total calcium if ionized calcium is unavailable 1

Additional Metabolic Assessment

• Serum electrolytes: Including sodium, potassium, and bicarbonate to assess for metabolic abnormalities 3
• Serum uric acid: May be elevated in primary hyperparathyroidism 3
• Urinalysis: Dipstick and microscopic evaluation to assess pH and identify crystals 3

Secondary Evaluation Based on Clinical Context

When Primary Hyperparathyroidism is Suspected

• 24-hour urine collection: Measure calcium, creatinine, and volume to assess urinary calcium excretion and stone risk 3
• Stone analysis: If kidney stones are present or available, obtain composition analysis at least once 3
• Imaging to quantify stone burden: Review or obtain imaging (CT, ultrasound) to assess for nephrolithiasis or nephrocalcinosis 3

Preoperative Localization Studies (if surgery is planned)

• Ultrasound and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT: Highly sensitive for localizing parathyroid adenomas before minimally invasive parathyroidectomy 2

Interpretation Algorithm

Primary Hyperparathyroidism Pattern

• Elevated calcium + elevated or inappropriately normal PTH = Primary hyperparathyroidism 1
• Confirm vitamin D status is adequate (≥20 ng/mL) before surgical decisions 1
• Assess for target organ damage: bone density, kidney stones, renal function 4

Secondary Hyperparathyroidism Pattern

• Low or normal calcium + elevated PTH = Secondary hyperparathyroidism 1
• Determine underlying cause: chronic kidney disease (check eGFR), vitamin D deficiency (check 25-OH vitamin D), malabsorption 1
• If vitamin D deficiency is present, supplement with cholecalciferol or ergocalciferol to achieve levels ≥30 ng/mL 5

Tertiary Hyperparathyroidism Pattern

• Elevated calcium + elevated PTH in the setting of chronic kidney disease or post-renal transplant = Tertiary hyperparathyroidism 6
• This represents autonomous PTH secretion after longstanding secondary hyperparathyroidism 6

Critical Pitfalls to Avoid

• Do not assume PTH elevation alone indicates primary hyperparathyroidism: The calcium level is essential for proper classification; elevated PTH with low-normal calcium suggests secondary hyperparathyroidism 1
• Do not start aggressive vitamin D supplementation in confirmed primary hyperparathyroidism without addressing the underlying parathyroid disease: This can worsen hypercalcemia 1
• Do not delay checking vitamin D levels: Vitamin D deficiency can mask the severity of hyperparathyroidism and must be corrected before making surgical decisions 1, 2
• Do not confuse primary with secondary hyperparathyroidism: The distinction is critical for appropriate management; primary requires consideration of surgery while secondary requires treatment of the underlying cause 1

Special Considerations in Chronic Kidney Disease

• In CKD stages 3-5, measure serum calcium, phosphorus, PTH, and 25-OH vitamin D levels regularly 3
• PTH levels between 100-500 pg/mL in CKD patients have insufficient sensitivity and specificity to reliably predict bone disease 5
• Parathyroidectomy should be considered when persistent serum intact PTH >800 pg/mL is associated with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 3