Evaluation and Management of Hyperparathyroidism
The evaluation of hyperparathyroidism requires measurement of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) simultaneously, followed by appropriate diagnostic imaging and treatment based on the type and severity of disease. 1, 2
Diagnostic Classification
- Hyperparathyroidism is classified into three main categories based on calcium levels: primary (elevated PTH with high/high-normal calcium), secondary (elevated PTH with normal/low calcium), and tertiary (persistent hypercalcemic hyperparathyroidism despite correction of underlying cause) 2
- Simultaneous measurement of serum calcium and intact PTH is essential for accurate diagnosis 1, 2
- Assessment of 25-OH vitamin D levels is crucial as deficiency can complicate interpretation of PTH levels and contribute to secondary hyperparathyroidism 1, 2
- Serum creatinine should be measured to assess kidney function, as chronic kidney disease is a common cause of secondary hyperparathyroidism 3
Initial Evaluation
- Measure serum calcium, phosphorus, and intact PTH simultaneously 1
- Assess 25-OH vitamin D levels, aiming for levels >20 ng/ml (50 mmol/l) 1
- Evaluate dietary calcium intake through dietary assessment 1
- Measure 24-hour urine calcium to quantify hypercalciuria and monitor treatment efficacy 1
- Screen for complications of hyperparathyroidism including kidney stones, bone disease, and neuromuscular symptoms 4
- Obtain imaging studies to quantify stone burden if kidney stones are suspected 3
- Consider genetic testing for CDC73 mutations in young patients with hyperparathyroidism, particularly if there is family history or jaw tumors suggesting hyperparathyroid-jaw tumor syndrome 3
Management of Primary Hyperparathyroidism
Surgical Management
- Parathyroidectomy is the only definitive cure for primary hyperparathyroidism and is recommended for symptomatic patients or those meeting surgical criteria. 5, 4
- Indications for parathyroidectomy include:
- Presence of symptoms (bone pain, kidney stones, abdominal discomfort, fatigue) 4
- Age 50 years or younger 4
- Serum calcium level more than 1 mg/dL above the upper limit of normal 4
- Osteoporosis 4
- Creatinine clearance less than 60 mL/minute per 1.73 m² 4
- Nephrolithiasis or nephrocalcinosis 4
- Hypercalciuria 4
- Preoperative localization with ultrasound and/or 99mTc-sestamibi scintigraphy with SPECT/CT is recommended 5
- Minimally invasive parathyroidectomy (MIP) offers shorter operating times and faster recovery compared to bilateral neck exploration 5
Medical Management
- For patients who cannot undergo surgery, medical options include:
- Cinacalcet is FDA-approved for treatment of hypercalcemia in primary hyperparathyroidism for patients who cannot undergo parathyroidectomy 6
- Starting dose is 30 mg twice daily, titrated every 2-4 weeks as needed to normalize calcium levels 6
- Monitor serum calcium within 1 week after initiation or dose adjustment 6
- Once maintenance dose is established, monitor calcium every 2 months 6
- Bisphosphonates and hormone replacement therapy may be considered for bone protection 7
- For asymptomatic patients not undergoing surgery:
Management of Secondary Hyperparathyroidism
- Identify and treat underlying causes (vitamin D deficiency, chronic kidney disease, malabsorption) 2
- For vitamin D deficiency:
- For chronic kidney disease-related secondary hyperparathyroidism:
- Dietary phosphate restriction and phosphate binders 5
- Correction of hypocalcemia 5
- For hemodialysis or peritoneal dialysis patients with PTH >300 pg/mL, administer active vitamin D sterols to target PTH levels of 150-300 pg/mL 2
- Cinacalcet may be used for dialysis patients with PTH >300 pg/mL, starting at 30 mg once daily 6
- Titrate cinacalcet no more frequently than every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily 6
- Monitor serum calcium and phosphorus every 2 weeks for 1 month after initiating or adjusting vitamin D therapy, then monthly 2
- Measure PTH monthly for 3 months, then every 3 months once target levels are achieved 2
Management of Tertiary Hyperparathyroidism
- Parathyroidectomy is indicated for patients with persistent hypercalcemia and elevated PTH despite correction of underlying causes 3
- Subtotal parathyroidectomy or total parathyroidectomy with autotransplantation are both effective surgical approaches 5
- For patients who cannot undergo surgery, cinacalcet may be considered 6
Special Considerations
- In patients with hyperparathyroidism-jaw tumor syndrome (HPT-JT):
- Begin surveillance at age 5-10 years for carriers of pathogenic CDC73 variants 3
- Include annual biochemical screening for hyperparathyroidism (total calcium, corrected for serum albumin) 3
- Obtain dental panoramic films every 5 years 3
- Perform renal ultrasound every 5 years 3
- Women of reproductive age should undergo routine gynecologic assessment with uterine ultrasound as clinically indicated 3
- In patients with recurrent kidney stones and hyperparathyroidism:
Post-Treatment Monitoring
- After parathyroidectomy:
- For patients on medical therapy:
Common Pitfalls to Avoid
- Not assessing vitamin D status when interpreting PTH levels can lead to misdiagnosis 2
- Using high doses of phosphate supplements (>80mg/kg daily based on elemental phosphorus) can worsen hyperparathyroidism 1
- Delaying surgical intervention in patients with symptomatic hyperparathyroidism can lead to progressive complications 5
- Using sodium citrate instead of potassium citrate for kidney stone prevention may increase urinary calcium excretion 5
- Biopsy of suspicious neck lesions in patients with hyperparathyroid-jaw tumor syndrome is discouraged due to risk of seeding carcinomatous cells 3