How is a patient with high parathyroid hormone (PTH) levels treated?

Treatment of High Parathyroid Hormone

The treatment of elevated PTH depends critically on whether you are dealing with primary hyperparathyroidism (PHPT) or secondary hyperparathyroidism (SHPT), with surgery being the only curative option for PHPT and medical management being first-line for SHPT in CKD patients on dialysis. 1, 2

Initial Diagnostic Confirmation

Before initiating any treatment, you must confirm the diagnosis biochemically by measuring serum calcium (corrected for albumin) and intact PTH simultaneously 1. Additionally, assess vitamin D status, as vitamin D deficiency can complicate PTH interpretation and cause secondary hyperparathyroidism 1. Be aware that PTH assays vary significantly between laboratories, so use assay-specific reference values when interpreting results 1.

Primary Hyperparathyroidism (PHPT)

Surgical Treatment - The Definitive Approach

Parathyroidectomy is the only curative treatment for PHPT and should be performed in patients meeting specific surgical criteria. 1, 2

Indications for surgery include: 1

• Symptomatic disease (kidney stones, bone pain, fractures, neuromuscular symptoms)
• Impaired kidney function (GFR < 60 mL/min/1.73 m²)
• Osteoporosis on DEXA scan
• Hypercalciuria

Choosing the Surgical Approach

Minimally invasive parathyroidectomy (MIP) is the preferred approach when preoperative imaging confidently localizes a single parathyroid adenoma, which accounts for 80-85% of PHPT cases. 2, 3 MIP offers shorter operating times, faster recovery, and decreased perioperative costs compared to bilateral neck exploration 1, 2, 3.

MIP requires two critical elements: 1, 2

• Confident preoperative localization of a single parathyroid adenoma
• Intraoperative PTH monitoring

Bilateral neck exploration (BNE) remains necessary when: 2, 3

• Preoperative imaging is discordant or nonlocalizing
• Multigland disease is suspected
• Hereditary HPT is present

Preoperative Imaging Strategy

Sestamibi (99Tc-Sestamibi) scan has the highest sensitivity for localizing parathyroid adenomas 1. Other options include ultrasound, 4-D parathyroid CT, and MRI 2. However, negative imaging is not a contraindication for parathyroid surgery and does not determine surgical indication—diagnosis is biochemical only. 2

Medical Management for Non-Surgical Candidates

For patients who cannot undergo or refuse surgery, medical management involves continual assessment to determine who will benefit from surgical intervention, replacement of vitamin D, treatment of parathyroid bone disease, and management of hypercalcemia and renal stone disease 4.

Cinacalcet can be used for hypercalcemia in PHPT patients for whom parathyroidectomy would be indicated based on serum calcium levels but who are unable to undergo surgery. 5 The recommended starting dose is 30 mg twice daily, titrated every 2 to 4 weeks through sequential doses up to 90 mg 3-4 times daily as necessary to normalize serum calcium levels 5.

Secondary Hyperparathyroidism (SHPT) in CKD Patients

Initial Medical Management - First-Line Approach

For SHPT in CKD patients on dialysis, begin with medical management including: 1, 3

• Dietary phosphate restriction
• Phosphate binders
• Correction of hypocalcemia with calcium supplementation
• Vitamin D sterols (calcitriol, paricalcitol, doxercalciferol) with dosage adjusted according to severity

For peritoneal dialysis patients specifically, oral doses of calcitriol (0.5-1.0 μg) or doxercalciferol (2.5-5.0 μg) can be given 2-3 times weekly. 3

Monitoring Requirements During Medical Therapy

Strict monitoring is essential: 1, 3

• Serum calcium and phosphorus every 2 weeks for 1 month after initiation or dose increase, then monthly
• PTH monthly for at least 3 months, then every 3 months once target levels achieved

Calcimimetic Therapy for Persistent SHPT

Cinacalcet may be considered for persistent secondary hyperparathyroidism despite initial therapy. 1, 5 Start at 30 mg once daily and titrate no more frequently than every 2-4 weeks to target iPTH levels of 150-300 pg/mL 1, 5. Exercise caution due to potential hypocalcemia and increased QT interval. 1, 3

During cinacalcet dose titration: 5

• Measure serum calcium and phosphorus within 1 week after initiation or dose adjustment
• Measure iPTH 1 to 4 weeks after initiation or dose adjustment
• Assess serum iPTH levels no earlier than 12 hours after dosing

If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, use calcium-containing phosphate binders and/or vitamin D sterols to raise serum calcium. 5 If serum calcium falls below 7.5 mg/dL or symptoms of hypocalcemia persist, withhold cinacalcet until serum calcium reaches 8 mg/dL and symptoms resolve, then reinitiate at the next lowest dose 5.

Surgical Intervention for Refractory SHPT

Parathyroidectomy should be recommended for severe hyperparathyroidism with persistent serum levels of intact PTH >800 pg/mL associated with hypercalcemia and/or hyperphosphatemia refractory to medical therapy. 3

Surgical options include: 3

• Subtotal parathyroidectomy
• Total parathyroidectomy with parathyroid tissue autotransplantation (TPTX + AT)
• Total parathyroidectomy (TPTX)

Total parathyroidectomy (TPTX) is superior to TPTX + AT regarding recurrence rates (OR = 0.20; 95%CI, 0.11-0.38; P < 0.01), with lower rates of reoperation due to recurrence or persistence (OR = 0.17; 95%CI, 0.06-0.54; P = 0.002) and shorter operative time 6. However, TPTX carries a higher risk of hypoparathyroidism (OR = 2.97; 95%CI, 1.09-8.08; P = 0.01), though no patients developed permanent hypocalcemia or adynamic bone disease in the meta-analysis 6.

Critical caveat: Avoid total parathyroidectomy in patients who may subsequently receive kidney transplant, as control of serum calcium levels may be problematic. 2, 3

Postoperative Management After Parathyroidectomy

Monitor ionized calcium every 4-6 hours for the first 48-72 hours after surgery, then twice daily until stable 3. Initiate calcium gluconate infusion and adjust phosphate binders as needed based on serum phosphorus levels 3.

Reoperative Cases (Persistent or Recurrent Disease)

For persistent or recurrent hyperparathyroidism, preoperative imaging with 99Tc-Sestamibi, ultrasound, CT, or MRI is mandatory prior to re-exploration. 2, 3 Reoperations have lower cure rates and higher complication rates than first-time surgery, making precise localization critical 2.