What is the initial approach to treating hyperparathyroidism?

Initial Approach to Treating Hyperparathyroidism

Surgery is the only definitive cure for primary hyperparathyroidism and should be performed in all symptomatic patients and most asymptomatic patients who meet surgical criteria. 1, 2

Diagnostic Confirmation and Initial Workup

Before initiating treatment, confirm the diagnosis and assess disease severity:

• Measure serum calcium (corrected for albumin) and intact parathyroid hormone (PTH) simultaneously to establish the diagnosis of hyperparathyroidism 1, 3
• Check 25-hydroxyvitamin D levels to exclude vitamin D deficiency as a concomitant secondary cause, aiming for levels >20 ng/mL (50 nmol/L) 1, 4
• Obtain 24-hour urine calcium measurement to assess calcium excretion and rule out familial hypocalciuric hypercalcemia 2
• Perform dual-energy x-ray absorptiometry (DEXA scan) to evaluate bone mineral density 2
• Assess renal function with serum creatinine and eGFR, as chronic kidney disease influences treatment decisions 4
• Evaluate dietary calcium intake through detailed dietary assessment 1, 4

Determining Treatment Strategy: Surgery vs. Observation

Indications for Parathyroidectomy

Surgery is indicated when any of the following criteria are met: 2, 5

• Symptomatic disease (bone pain, fractures, kidney stones, neurocognitive symptoms) 1, 2
• Age ≤50 years 2, 5
• Serum calcium >1 mg/dL above the upper limit of normal 2, 5
• Creatinine clearance <60 mL/min/1.73 m² 2, 5
• Osteoporosis (T-score ≤-2.5 at any site) 2, 5
• Nephrolithiasis or nephrocalcinosis 1, 5
• Hypercalciuria (>400 mg/24 hours) 5

Preoperative Imaging

Perform cervical ultrasonography and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT for operative planning to facilitate minimally invasive parathyroidectomy 6, 2. The combination of both modalities increases localization accuracy 6, 7. Patients with nonlocalizing imaging remain surgical candidates for bilateral neck exploration 2.

Surgical Approach

Two acceptable surgical options exist: 1, 2

• Minimally invasive parathyroidectomy (MIP) with intraoperative PTH monitoring for single adenomas with concordant preoperative imaging 1, 2
• Bilateral neck exploration (BNE) for multigland disease, nonlocalizing imaging, or discordant imaging 1, 2

MIP offers shorter operating times, faster recovery, and decreased costs but requires confident preoperative localization 6, 2. Intraoperative PTH monitoring via a reliable protocol is recommended during MIP 2.

Medical Management for Non-Surgical Candidates

For patients who cannot undergo surgery or decline surgery despite meeting criteria: 8

• Cinacalcet (calcimimetic) is FDA-approved for hypercalcemia in primary hyperparathyroidism when parathyroidectomy would be indicated but patients are unable to undergo surgery 8
• Starting dose: 30 mg twice daily orally with food, titrated every 2-4 weeks through sequential doses (30 mg twice daily → 60 mg twice daily → 90 mg twice daily → 90 mg 3-4 times daily) to normalize serum calcium 8
• Monitor serum calcium within 1 week after initiation or dose adjustment, then every 2 months once stable 8

Important Caveats for Cinacalcet

• Risk of hypocalcemia requires careful monitoring; ensure corrected serum calcium is at or above the lower limit of normal before initiation 8
• Common adverse effects include nausea (63%), vomiting (46%), and hypocalcemia (11%) 8
• Not a substitute for surgery in appropriate surgical candidates; surgery remains more cost-effective than pharmacologic therapy 2

Secondary Hyperparathyroidism Management

For secondary hyperparathyroidism (elevated PTH with normal or low calcium due to chronic kidney disease or vitamin D deficiency): 4

• Supplement with native vitamin D (cholecalciferol or ergocalciferol) if 25-OH vitamin D is <20 ng/mL 1, 4
• Ensure adequate dietary calcium intake (adults >24 years: 950 mg/day) 4
• For CKD patients on dialysis with persistently elevated PTH, administer active vitamin D sterols (calcitriol, alfacalcidol) to target PTH 150-300 pg/mL 4
• Avoid cinacalcet in CKD patients not on dialysis due to increased risk of hypocalcemia 8

Post-Operative Monitoring

After parathyroidectomy: 1

• Monitor ionized calcium every 4-6 hours for the first 48-72 hours, then twice daily until stable 1
• Initiate calcium gluconate infusion if calcium falls below normal 1
• Provide oral calcium carbonate and calcitriol when oral intake is possible 1
• Assess for cure with eucalcemia at >6 months post-operatively 2

Common Pitfalls to Avoid

• Do not perform preoperative parathyroid biopsy—it should be avoided 2
• Do not delay surgery in symptomatic patients or those meeting surgical criteria, as this can lead to progressive bone loss and renal complications 1
• Do not use calcimimetics as first-line therapy when surgery is appropriate and feasible 2
• Do not assume all hyperparathyroidism is primary—always exclude secondary causes (vitamin D deficiency, CKD, malabsorption) 4, 5