Treatment of Abnormal Parathyroid Hormone (PTH) Levels
Initial Diagnostic Approach
The first critical step when encountering abnormal PTH is to simultaneously measure serum calcium (corrected for albumin) and assess vitamin D status, as this determines whether you are dealing with primary hyperparathyroidism, secondary hyperparathyroidism, hypoparathyroidism, or normocalcemic primary hyperparathyroidism. 1
Essential Laboratory Workup
- Measure serum calcium (corrected for albumin) or ionized calcium, intact PTH, 25-hydroxyvitamin D level, serum creatinine with estimated GFR, serum phosphorus, and 24-hour urine calcium or spot urine calcium/creatinine ratio simultaneously 1
- PTH assays vary significantly between laboratories with up to 47% variation between different assay generations, so always use assay-specific reference values 1
- PTH reference values are 20% lower in vitamin D-replete individuals compared to those with unknown vitamin D status 1
- Recognize that PTH varies by 20% in healthy individuals, so differences must exceed 54% to be clinically significant 1
Management of Elevated PTH with Hypercalcemia (Primary Hyperparathyroidism)
Parathyroidectomy is the only curative treatment for primary hyperparathyroidism and should be performed in patients meeting surgical criteria. 1, 2
Surgical Indications
Proceed with parathyroidectomy if any of the following criteria are met: 1, 2
- Corrected calcium >1 mg/dL above upper limit of normal
- Age <50 years
- Impaired kidney function (GFR <60 mL/min/1.73 m²)
- Osteoporosis (T-score ≤-2.5 at any site)
- History of nephrolithiasis or nephrocalcinosis
- Hypercalciuria (>300 mg/24hr)
- Symptomatic disease including bone pain, fractures, or neuromuscular symptoms
Preoperative Imaging
- Obtain ultrasound and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT for localization before surgery 2
- Do not order parathyroid imaging before confirming biochemical diagnosis, as imaging is for surgical planning, not diagnosis 1
Non-Surgical Management
For patients who do not meet surgical criteria or are not surgical candidates: 1
- Maintain normal calcium intake (1000-1200 mg/day)
- Ensure adequate vitamin D (>20 ng/mL) with supplementation if needed
- Monitor serum calcium every 3 months
- Do not treat with vitamin D if serum calcium >10.2 mg/dL, as this can worsen hypercalcemia and increase risk of vascular calcification 1
Management of Elevated PTH in CKD Patients (Secondary Hyperparathyroidism)
CKD Stage 3a-5 (Not on Dialysis)
In patients with CKD G3a-G5 not on dialysis, evaluate progressively rising or persistently elevated PTH for modifiable factors including hyperphosphatemia, hypocalcemia, high phosphate intake, and vitamin D deficiency. 3
- Calcitriol and vitamin D analogs should not be routinely used in CKD G3a-G5 not on dialysis 3
- Reserve calcitriol and vitamin D analogs for patients with CKD G4-G5 with severe and progressive hyperparathyroidism 3
CKD Stage 5D (On Dialysis)
Target intact PTH levels in the range of approximately 2 to 9 times the upper normal limit for the assay (approximately 150-600 pg/mL for most assays). 3, 4
Initial Medical Management
Start with the following stepwise approach: 1, 4
- Dietary phosphate restriction
- Phosphate binders (restrict dose of calcium-based binders to avoid hypercalcemia) 3
- Correction of hypocalcemia with calcium supplementation
- Vitamin D sterols (calcitriol, paricalcitol, doxercalciferol) with dosage adjusted according to severity
Second-Line Therapy: Calcimimetics
For persistent secondary hyperparathyroidism despite initial therapy: 1, 4
- Start cinacalcet 30 mg once daily
- Titrate no more frequently than every 2-4 weeks to target iPTH of 150-300 pg/mL
- Monitor serum calcium and phosphorus every 2 weeks for 1 month after initiation or dose increase, then monthly
- Monitor PTH monthly for at least 3 months, then every 3 months once target levels achieved
Surgical Management
Parathyroidectomy should be recommended for patients with severe hyperparathyroidism (persistent serum levels of intact PTH >800 pg/mL) associated with hypercalcemia and/or hyperphosphatemia that are refractory to medical therapy. 3, 4
Effective surgical options include: 3
- Subtotal parathyroidectomy
- Total parathyroidectomy with parathyroid tissue autotransplantation (higher risk of hypoparathyroidism but lower recurrence rates) 4
Critical Pitfalls in CKD Management
- Do not over-suppress PTH in CKD patients, as intact PTH levels below 150 pg/mL are associated with adynamic bone disease, which increases risk of hypercalcemia and vascular calcification 1
- Marked changes in PTH levels in either direction within the target range should prompt initiation or change in therapy to avoid progression to levels outside this range 3
Management of Low PTH (Hypoparathyroidism)
For hypoparathyroidism, initiate aggressive calcium and vitamin D supplementation immediately, even before laboratory confirmation if clinical suspicion is high. 2
Standard Treatment
- Oral calcium supplementation (typically calcium carbonate)
- Calcitriol (active vitamin D)
- Target serum calcium in the low-normal range to avoid hypercalciuria
PTH Replacement Therapy
- PTH(1-84) 100 µg every other day by subcutaneous injection significantly reduces supplemental calcium and 1,25-dihydroxyvitamin D requirements 5
- This therapy is reserved for patients who cannot be adequately controlled on conventional therapy
Post-Parathyroidectomy Monitoring
After parathyroidectomy, monitor for "hungry bone syndrome": 3, 2
- Measure ionized calcium every 4-6 hours for the first 48-72 hours after surgery, then twice daily until stable
- Initiate calcium gluconate infusion if calcium levels fall below normal
- Provide calcium carbonate and calcitriol when oral intake is possible
- Adjust phosphate binders based on serum phosphorus levels
Special Considerations for Post-Kidney Transplant Patients
Monitor calcium, phosphate, and PTH based on CKD stage: 3
- CKD G1T-G3bT: Calcium and phosphate every 6-12 months; PTH once, with subsequent intervals depending on baseline level
- CKD G4T: Calcium and phosphate every 3-6 months; PTH every 6-12 months
- CKD G5T: Calcium and phosphate every 1-3 months; PTH every 3-6 months
Manage abnormalities as for patients with CKD G3a-G5 3