What is the initial evaluation and treatment approach for a patient with hyperparathyroidism?

Initial Evaluation and Treatment of Hyperparathyroidism

The initial evaluation requires simultaneous measurement of serum calcium and intact PTH to differentiate primary from secondary hyperparathyroidism, followed by assessment of vitamin D status, renal function, and phosphorus levels—with definitive treatment being parathyroidectomy for primary hyperparathyroidism and medical management targeting the underlying cause for secondary hyperparathyroidism. 1

Initial Diagnostic Workup

Essential Laboratory Tests

The cornerstone of diagnosis requires these simultaneous measurements 1:

• Serum calcium and intact PTH (iPTH) measured together to distinguish PTH-dependent from PTH-independent hypercalcemia 1
• Serum albumin to correct total calcium if ionized calcium is unavailable 1
• Serum phosphorus (typically low in primary hyperparathyroidism) 1
• 25-hydroxyvitamin D levels targeting ≥20 ng/mL (≥50 nmol/L), as vitamin D deficiency can mask hyperparathyroidism severity 1
• Serum creatinine and eGFR to distinguish primary from CKD-related secondary hyperparathyroidism 1

Diagnostic Interpretation

Primary hyperparathyroidism: Elevated calcium with elevated or inappropriately normal PTH 1, 2, 3

Secondary hyperparathyroidism: Low or normal calcium with elevated PTH, commonly due to chronic kidney disease or vitamin D deficiency 1, 4

Tertiary hyperparathyroidism: Hypercalcemia with elevated PTH after longstanding secondary hyperparathyroidism, typically post-kidney transplant 5, 4

Additional Evaluation When Indicated

• 24-hour urine collection for calcium, creatinine, and volume to assess urinary calcium excretion and stone risk 1
• Imaging for nephrolithiasis/nephrocalcinosis if clinically suspected 1
• PTH-related protein (PTHrP) if malignancy-associated hypercalcemia suspected 1

Treatment Approach by Type

Primary Hyperparathyroidism

Surgical excision is the only definitive cure for primary hyperparathyroidism. 6, 2, 3

Preoperative Localization Imaging

Multiple imaging modalities are typically equivalent alternatives, though they may be used complementarily to maximize accuracy 7:

• Ultrasound of parathyroid glands 7
• 99mTc-sestamibi dual-phase scan with SPECT or SPECT/CT 7
• 4-D parathyroid CT (neck CT without and with IV contrast) using multiphase technique leveraging unique perfusion characteristics 7

The ACR Appropriateness Criteria note there is no universally accepted algorithm, and selection should consider surgeon/radiologist preference, regional expertise, and patient characteristics (suspected multigland disease, hereditary causes, concomitant thyroid disease) 7

Surgical Options

• Minimally invasive parathyroidectomy (MIP) or bilateral neck exploration (BNE) 6
• Surgery is indicated for symptomatic disease or asymptomatic patients meeting guideline criteria 6, 3

Medical Management for Non-Surgical Candidates

Cinacalcet is FDA-approved for primary hyperparathyroidism when parathyroidectomy would be indicated based on serum calcium levels but patients cannot undergo surgery. 8

• Starting dose: 30 mg twice daily 8
• Titrate every 2-4 weeks through sequential doses (30 mg BID → 60 mg BID → 90 mg BID → 90 mg 3-4 times daily) to normalize serum calcium 8
• Measure serum calcium within 1 week after initiation or dose adjustment 8
• Once maintenance dose established, monitor serum calcium every 2 months 8

Secondary Hyperparathyroidism

For CKD Stages 3-5 (Not on Dialysis)

First, evaluate and correct modifiable factors 6:

• Assess for hyperphosphatemia, hypocalcemia, high phosphate intake, and vitamin D deficiency 6
• Supplement with vitamin D to achieve 25-OH vitamin D >20 ng/mL if deficient 9, 6
• Control serum phosphorus through dietary restriction and phosphate binders 6
• Restrict calcium-based phosphate binders to avoid hypercalcemia 6

Calcitriol and vitamin D analogs should NOT be routinely used in CKD G3a-G5 not on dialysis 6

Reserve active vitamin D therapy only for CKD G4-G5 with severe and progressive hyperparathyroidism 6

For Dialysis Patients (CKD G5D)

When intact PTH >300 pg/mL 6:

• Administer active vitamin D sterol (calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) to reduce PTH to 150-300 pg/mL 6
• Intermittent IV calcitriol is more effective than daily oral calcitriol for lowering PTH 9, 6
• Target PTH range: approximately 2-9 times the upper normal limit for the assay 6

Cinacalcet is FDA-approved for secondary hyperparathyroidism in CKD patients on dialysis 8:

• Starting dose: 30 mg once daily 8
• Titrate every 2-4 weeks through sequential doses (30 → 60 → 90 → 120 → 180 mg once daily) to target iPTH 150-300 pg/mL 8
• Can be used alone or with vitamin D sterols and/or phosphate binders 8

Monitoring During Medical Therapy

• Serum calcium and phosphorus: Every 2 weeks for 1 month after initiation/dose adjustment, then monthly 6, 8
• PTH: Monthly for at least 3 months, then every 3 months once target achieved 6, 8

Surgical Management for Refractory Cases

Consider parathyroidectomy when persistent iPTH >800 pg/mL is associated with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 1, 6

Surgical options 6:

• Subtotal parathyroidectomy
• Total parathyroidectomy with autotransplantation
• Total parathyroidectomy (may have lower recurrence rates than with autotransplantation) 6

Tertiary Hyperparathyroidism

Tertiary hyperparathyroidism occurs after longstanding secondary hyperparathyroidism, most commonly post-kidney transplant, characterized by persistent PTH elevation despite hypercalcemia 7, 5, 4

• Surgical excision is recommended for medically refractory cases 7
• Imaging goal is to identify all eutopic and potential ectopic/supernumerary glands due to typical multigland disease 7

Critical Management Pitfalls to Avoid

• Do NOT use cinacalcet in CKD patients not on dialysis due to increased hypocalcemia risk 8
• Do NOT assume low PTH means hypoparathyroidism without full clinical context 1
• Do NOT start aggressive vitamin D supplementation in primary hyperparathyroidism before addressing the parathyroid pathology 1
• Do NOT confuse primary with secondary hyperparathyroidism—the calcium level is the key differentiator 1
• Do NOT ignore vitamin D deficiency as it can coexist with and mask primary hyperparathyroidism severity 1, 3

Hypocalcemia Monitoring and Management

If serum calcium falls below 8.4 mg/dL but remains >7.5 mg/dL during cinacalcet therapy 8:

• Use calcium-containing phosphate binders and/or vitamin D sterols to raise calcium 8

If serum calcium falls below 7.5 mg/dL or symptoms persist 8:

• Withhold cinacalcet until calcium reaches 8 mg/dL and symptoms resolve 8
• Reinitiate at next lowest dose 8