How should I evaluate and manage a child with elevated parathyroid hormone levels?

Evaluation and Management of Elevated Parathyroid Hormone in Children

The first priority is to determine whether this represents primary hyperparathyroidism (with elevated or inappropriately normal PTH plus hypercalcemia) versus secondary hyperparathyroidism (with elevated PTH but normal or low calcium), as this distinction fundamentally determines management—primary disease requires surgical evaluation while secondary disease requires medical optimization of the underlying cause. 1

Initial Diagnostic Workup

Measure these laboratory tests simultaneously to establish the diagnosis:

• Serum calcium (corrected for albumin) and ionized calcium to distinguish primary from secondary hyperparathyroidism 1, 2
• Intact parathyroid hormone (PTH) using EDTA plasma rather than serum, as PTH is most stable in EDTA plasma at 4°C 1
• Serum phosphorus, which is typically low-normal in primary hyperparathyroidism and elevated in secondary hyperparathyroidism related to chronic kidney disease 1, 2
• 25-hydroxyvitamin D levels, as vitamin D deficiency (levels <20 ng/mL) is the most common cause of secondary hyperparathyroidism and must be excluded 1, 2
• Serum creatinine and estimated GFR to assess kidney function, as chronic kidney disease is a major cause of secondary hyperparathyroidism 1, 2
• Alkaline phosphatase to assess bone turnover 3
• 24-hour urine calcium or spot urine calcium/creatinine ratio to evaluate urinary calcium excretion 1, 4

Critical measurement consideration: PTH assays vary by up to 47% between different generations, so always use assay-specific reference values and measure PTH trends over time rather than relying on single values 1

Diagnostic Algorithm Based on Calcium Levels

If Calcium is Elevated (>10.2 mg/dL): Primary Hyperparathyroidism

Primary hyperparathyroidism is confirmed by elevated or inappropriately normal PTH in the presence of hypercalcemia. 1, 4

Before confirming the diagnosis, exclude these secondary causes:

• Vitamin D deficiency: Ensure 25-hydroxyvitamin D is >20 ng/mL (>50 nmol/L), as deficiency causes secondary hyperparathyroidism that can confound the diagnosis 1
• Inadequate dietary calcium intake: Confirm the child is receiving age-appropriate calcium intake (infants 0-6 months: 200 mg/day; 1-3 years: 700 mg; 4-8 years: 1,000 mg; 9-18 years: 1,300 mg) 5
• Medications: Discontinue any calcium supplements, vitamin D supplements, or thiazide diuretics 1

Immediate actions for primary hyperparathyroidism:

• Refer to pediatric endocrinology and an experienced parathyroid surgeon for evaluation, as solitary parathyroid adenoma is the most common cause in children and requires surgical excision 1, 4
• Obtain renal ultrasonography to screen for nephrocalcinosis or kidney stones 1
• Obtain bone density assessment if chronic disease is suspected 1
• Perform fundoscopic examination to rule out papilledema before any growth hormone therapy consideration 5

Surgical indications include: corrected calcium >1 mg/dL above upper limit of normal, age <50 years (which includes all children), impaired kidney function (eGFR <60 mL/min/1.73 m²), osteoporosis, nephrolithiasis, nephrocalcinosis, or symptomatic disease 1, 2

Common pitfall: In children, parathyroid hyperplasia is more common than adenoma in neonates and infants, making surgical planning more complex 6

If Calcium is Normal or Low: Secondary Hyperparathyroidism

Secondary hyperparathyroidism is characterized by elevated PTH with normal or low serum calcium, most commonly due to chronic kidney disease, vitamin D deficiency, or disorders of phosphate metabolism. 7, 2

Determine the underlying cause:

• Chronic kidney disease: If eGFR <60 mL/min/1.73 m², this is the likely cause 7, 2
• Vitamin D deficiency: If 25-hydroxyvitamin D <30 ng/mL, this contributes significantly 7, 2
• Hypophosphatemic rickets (X-linked hypophosphatemia): If serum phosphorus is low with elevated alkaline phosphatase, consider this diagnosis 5
• Malabsorption disorders: Consider chronic intestinal malabsorption, hepatobiliary disease, or vitamin D-dependent rickets 6
• Iatrogenic causes: Excessive phosphate supplementation in familial hypophosphatemic rickets can cause secondary hyperparathyroidism 6

Management of Secondary Hyperparathyroidism

For Vitamin D Deficiency (Most Common Cause)

Supplement with ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3):

• If 25-hydroxyvitamin D <30 ng/mL: Provide ergocalciferol 50,000 IU monthly or equivalent daily dosing 7
• Target 25-hydroxyvitamin D levels >30 ng/mL to prevent aggravation of secondary hyperparathyroidism 7
• Recheck 25-hydroxyvitamin D annually once replete 7

For Chronic Kidney Disease-Related Secondary Hyperparathyroidism

The management algorithm differs significantly by CKD stage:

For CKD Stage 3 (eGFR 30-59 mL/min/1.73 m²):

• Measure calcium, phosphorus, and PTH at baseline 7
• Maintain phosphorus in normal range (2.7-4.6 mg/dL) through dietary restriction if elevated 7
• Replete vitamin D with ergocalciferol if 25-hydroxyvitamin D <30 ng/mL 7
• Do NOT initiate active vitamin D therapy (calcitriol) unless PTH continues rising despite vitamin D repletion, as aggressive suppression risks adynamic bone disease 7
• Monitor calcium and phosphorus every 3 months 7

For CKD Stage 4-5 or Dialysis:

• Target PTH levels of 150-300 pg/mL (NOT normal range), as suppressing PTH to <65 pg/mL causes adynamic bone disease with increased fracture risk 7, 3
• Control hyperphosphatemia FIRST before initiating active vitamin D therapy 7
  • Target phosphorus 3.5-5.5 mg/dL for stage 5 CKD 7
  • Initiate dietary phosphorus restriction to 800-1,000 mg/day 7
  • Use phosphate binders (calcium carbonate 1-2 g three times daily with meals) 7
• Do NOT start active vitamin D until phosphorus <4.6 mg/dL, as this worsens vascular calcification 7
• Once phosphorus is controlled, initiate active vitamin D therapy:
  • Calcitriol or paricalcitol, with intermittent intravenous administration more effective than oral in dialysis patients 7
  • Adjust dosage according to severity of hyperparathyroidism 7
• Monitor calcium and phosphorus monthly initially, then every 3 months 7
• Monitor PTH every 3 months 7
• Discontinue all vitamin D therapy if calcium rises above 10.2 mg/dL 7

Critical pitfall: Starting active vitamin D with uncontrolled hyperphosphatemia worsens vascular calcification and increases calcium-phosphate product, which should never exceed 70 mg²/dL² 7

For X-Linked Hypophosphatemia (XLH)

If the child has hypophosphatemia with elevated PTH and alkaline phosphatase, consider XLH:

• Marked secondary hyperparathyroidism should be controlled before growth hormone therapy is commenced 5
• Maintain serum PTH levels within CKD-stage-dependent target range 5
• Keep serum 25-hydroxyvitamin D3 concentrations above 30 ng/mL 5
• Treatment with oral phosphate should always be combined with active vitamin D to prevent secondary hyperparathyroidism 5
• Adjust doses by reducing phosphate or increasing active vitamin D to maintain PTH, serum calcium, and urinary calcium within normal range 5
• Consider calcimimetics (cinacalcet) off-label for persistently elevated PTH despite optimized therapy, though data in combination with burosumab are lacking 5

Monitoring and Follow-Up

For all children with elevated PTH:

• Measure serum calcium every 3-4 months until diagnosis is established and treatment optimized 1
• Monitor growth parameters closely, as secondary hyperparathyroidism can impair linear growth 5
• Assess pubertal development in children >10 years, as delayed puberty may occur with chronic disease 5
• Perform renal ultrasonography to screen for nephrocalcinosis 1

When to Consider Parathyroidectomy

Parathyroidectomy should be considered in these scenarios:

• Primary hyperparathyroidism meeting surgical criteria (essentially all symptomatic children) 1, 4
• Tertiary hyperparathyroidism (persistent hypercalcemic hyperparathyroidism despite correction of underlying cause) 8, 6
• Severe secondary hyperparathyroidism with PTH persistently >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy after 3-6 months of optimized treatment 7

Post-parathyroidectomy care:

• Monitor ionized calcium every 4-6 hours for the first 48-72 hours, then twice daily until stable 7, 8
• Provide calcium and calcitriol supplementation to prevent hypocalcemia, which is common postoperatively 7, 4

Common Pitfalls to Avoid

• Not measuring vitamin D status before diagnosing primary hyperparathyroidism, as vitamin D deficiency causes secondary hyperparathyroidism that mimics primary disease 1
• Ordering parathyroid imaging before confirming biochemical diagnosis, as imaging is for surgical planning, not diagnosis 1
• Starting active vitamin D therapy with uncontrolled hyperphosphatemia in CKD patients, which worsens vascular calcification 7
• Targeting normal PTH levels (<65 pg/mL) in dialysis patients, which causes adynamic bone disease 7, 3
• Relying on single PTH measurements rather than trends, as biological variation is substantial (20% in healthy individuals) 1
• Using high doses of phosphate supplements (>80 mg/kg daily) in XLH, which can worsen hyperparathyroidism 8