What are the treatment options for parathyroid hormone imbalances?

Treatment Options for Parathyroid Hormone Imbalances

The treatment of PTH imbalances depends fundamentally on whether you are dealing with hyperparathyroidism (primary, secondary, or tertiary) or hypoparathyroidism, with surgical parathyroidectomy being the only definitive cure for primary hyperparathyroidism, while secondary hyperparathyroidism requires medical management targeting the underlying cause. 1

Primary Hyperparathyroidism

Surgical excision of abnormal parathyroid tissue is the only definitive cure for primary hyperparathyroidism. 1 Surgery is indicated when patients have symptomatic disease, including recurrent renal stones, hypercalcemia refractory to medical therapy, or persistent intact PTH >800 pg/mL with hypercalcemia. 1

Surgical Approaches

• Minimally invasive parathyroidectomy (MIP) is preferred over bilateral neck exploration when feasible, offering shorter operating times, faster recovery, and decreased costs. 1
• Both subtotal parathyroidectomy and total parathyroidectomy with autotransplantation are effective surgical options. 2, 1
• Preoperative imaging with ultrasound and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT is highly sensitive for localizing parathyroid adenomas and should be performed before surgery. 1

Medical Management When Surgery is Contraindicated

• Cinacalcet is indicated for hypercalcemia in adult patients with primary hyperparathyroidism when parathyroidectomy would be indicated based on serum calcium levels but patients cannot undergo surgery. 3
• Ensure adequate hydration and consider thiazide diuretics for patients with high urinary calcium and recurrent calcium stones. 1

Secondary Hyperparathyroidism

Chronic Kidney Disease-Related SHPT

Initial treatment includes dietary phosphate restriction, phosphate binders, correction of hypocalcemia, and vitamin D supplementation. 1 The 2017 KDIGO guidelines represent a significant shift from earlier recommendations, emphasizing that modest PTH elevations may be an appropriate adaptive response to declining kidney function. 2

Treatment Algorithm for CKD Patients:

• Do not treat based on a single elevated PTH value; modest increases in PTH (up to several times the upper limit of normal) may represent appropriate adaptation to declining kidney function. 2
• Reserve calcitriol or vitamin D analogs only for severe and progressive SHPT, not for routine use in CKD stages 3a-5. 2 This recommendation changed from 2009 guidelines after the PRIMO and OPERA trials demonstrated increased hypercalcemia risk without cardiac benefits. 2
• For dialysis patients with intact PTH >300 pg/mL (33.0 pmol/L), use active vitamin D sterols (calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) to reduce PTH to target range of 150-300 pg/mL. 2
• Intermittent intravenous calcitriol is more effective than daily oral calcitriol for lowering serum PTH levels in dialysis patients. 2

Calcimimetics:

• Cinacalcet is indicated for secondary hyperparathyroidism in adult CKD patients on dialysis. 3
• Cinacalcet should be started when PTH reaches 85 pmol/L (approximately 802 pg/mL, ~10× the upper reference limit) and SHPT is refractory to other treatments with surgery contraindicated. 2
• Critical pitfall: Cinacalcet is NOT indicated for CKD patients not on dialysis due to increased risk of hypocalcemia. 3

Monitoring Requirements:

• When initiating or increasing vitamin D sterols, measure serum calcium and phosphorus at least every 2 weeks for 1 month, then monthly thereafter. 2
• Measure PTH monthly for at least 3 months, then every 3 months once target levels are achieved. 2

Vitamin D Deficiency-Related SHPT

• Supplement with cholecalciferol or ergocalciferol to achieve 25-OH vitamin D levels ≥30 ng/mL. 4
• Recheck PTH every 3 months for 6 months, then every 3-6 months to assess response to vitamin D repletion. 4
• Ensure adequate dietary calcium intake meeting age-related recommended dietary allowances. 1, 4

Post-Bariatric Surgery SHPT

• Monitor PTH regularly after bariatric surgery to evaluate for calcium and vitamin D deficiency, as prevalence of SHPT can reach 63% at 5 years depending on surgery type. 2
• PTH >6.9 pmol/L (65 pg/mL) indicates calcium or vitamin D deficiency requiring supplementation. 2

Tertiary Hyperparathyroidism

• Parathyroidectomy is indicated for persistent hypercalcemic hyperparathyroidism despite optimized medical therapy in patients with CKD. 5
• This represents autonomous PTH secretion that has developed after prolonged secondary hyperparathyroidism. 6

Hypoparathyroidism

Acute Management (Post-Surgical)

Post-parathyroidectomy hypocalcemia requires aggressive monitoring and treatment to prevent life-threatening complications. 1

• Measure ionized calcium every 4-6 hours for the first 48-72 hours after surgery, then twice daily until stable. 2, 1
• If ionized calcium falls below 0.9 mmol/L (3.6 mg/dL), initiate calcium gluconate infusion at 1-2 mg elemental calcium per kg body weight per hour. 2
• When oral intake is possible, provide calcium carbonate 1-2 g three times daily plus calcitriol up to 2 μg/day. 2
• Discontinue or reduce phosphate binders as dictated by serum phosphorus levels. 2

Chronic Management

• Treat chronic hypoparathyroidism with combination of calcium supplements, vitamin D analogs, and occasionally exogenous PTH. 6
• PTH(1-84) treatment at 100 μg every other day by subcutaneous injection significantly reduces supplemental calcium and 1,25-dihydroxyvitamin D requirements without generally altering serum and urinary calcium levels. 7

Adynamic Bone Disease

• When intact PTH is <100 pg/mL (11.0 pmol/L) in stage 5 CKD, allow PTH to rise by decreasing or eliminating calcium-based phosphate binders and vitamin D therapy to increase bone turnover. 2
• Critical pitfall: Over-suppression of PTH (intact PTH <150 pg/mL) is associated with high incidence of adynamic bone disease. 4

Key Treatment Pitfalls to Avoid

• Never treat PTH elevation alone without assessing calcium levels, as calcium determines whether hyperparathyroidism is primary or secondary. 4
• Avoid vitamin D sterols when serum phosphorus exceeds 6.5 mg/dL due to risk of further elevating phosphorus. 4
• Do not state absolute PTH cutoff values in clinical practice without specifying the assay used, as PTH concentrations differ significantly between assays even of the same generation. 2
• Do not delay surgical intervention in patients with recurrent renal stones and hyperparathyroidism, as this leads to progressive renal damage. 1
• Recognize that "hungry bone syndrome" can cause late-onset hypocalcemia weeks after parathyroidectomy when previously suppressed bone rapidly remineralizes. 1