How should I evaluate and manage a patient with an elevated parathyroid hormone level?

Evaluation and Management of Elevated PTH

Begin by measuring serum calcium, 25-hydroxyvitamin D, serum phosphorus, and estimated GFR simultaneously—this single panel will distinguish primary hyperparathyroidism from the far more common secondary causes and guide all subsequent management. 1, 2

Initial Diagnostic Algorithm

Step 1: Measure the Essential Four Tests Together

• Serum calcium (corrected for albumin) – determines whether PTH elevation is appropriate (normocalcemia) or autonomous (hypercalcemia) 1, 3
• Intact PTH – use EDTA plasma rather than serum for most stable measurement 1
• 25-hydroxyvitamin D – deficiency (<30 ng/mL) is the most frequently missed reversible cause of elevated PTH 1, 2
• Serum creatinine/eGFR – age-related GFR decline is the most common cause of isolated PTH elevation in older adults 2

Add serum phosphorus to distinguish primary hyperparathyroidism (typically low-normal) from CKD-related secondary hyperparathyroidism (typically elevated). 1, 2

Step 2: Interpret the Pattern

If calcium is elevated (>10.2 mg/dL) with elevated or inappropriately normal PTH:

• This is primary hyperparathyroidism – the parathyroid glands autonomously secrete PTH despite hypercalcemia 1, 3
• Confirm vitamin D status is >20 ng/mL to exclude vitamin D deficiency masking the diagnosis 1
• Refer immediately to endocrinology and an experienced high-volume parathyroid surgeon for surgical evaluation 1, 3

If calcium is normal with elevated PTH:

This represents either secondary hyperparathyroidism (appropriate PTH response) or normocalcemic primary hyperparathyroidism (autonomous PTH secretion). 2, 4

• First, correct vitamin D deficiency – supplement with cholecalciferol or ergocalciferol to achieve 25-OH vitamin D ≥30 ng/mL before any other intervention 2
• Second, assess kidney function – in elderly patients, age-related GFR decline is the most frequent cause; PTH rises early in CKD, often before calcium or phosphorus abnormalities appear 2
• Third, ensure adequate dietary calcium intake (1000-1200 mg/day) – low intake can mimic secondary hyperparathyroidism 1, 2
• Repeat PTH after 3 months – PTH has 20% biological variability in healthy individuals, so a single measurement is insufficient 1, 2

Only diagnose normocalcemic primary hyperparathyroidism after excluding all secondary causes and confirming persistent elevation on repeat testing. 1, 4

Surgical Indications for Primary Hyperparathyroidism

Refer for parathyroidectomy if any of the following criteria are met: 1, 3

• Corrected calcium >1 mg/dL above upper limit of normal (>11.2 mg/dL)
• Age <50 years
• eGFR <60 mL/min/1.73 m²
• Osteoporosis (T-score ≤-2.5 at any site)
• History of nephrolithiasis or nephrocalcinosis
• 24-hour urinary calcium >300 mg (severe hypercalciuria)
• Disabling neuropsychiatric symptoms (refractory depression, cognitive impairment, "brain fog")
• Patient preference for definitive treatment

Parathyroidectomy is the only definitive cure and is recommended even in asymptomatic patients because prolonged disease produces adverse metabolic effects. 1, 3

Management of Secondary Hyperparathyroidism

For Vitamin D Deficiency (Most Common Cause)

• Supplement with cholecalciferol or ergocalciferol to achieve 25-OH vitamin D ≥30 ng/mL 1, 2
• Do not use calcitriol or active vitamin D analogs in primary hyperparathyroidism—they increase intestinal calcium absorption and worsen hypercalcemia 1
• Monitor serum calcium monthly for the first 3 months during supplementation; discontinue immediately if calcium exceeds 10.2 mg/dL 1

For CKD-Related Secondary Hyperparathyroidism

• Correct modifiable factors first: hyperphosphatemia, hypocalcemia, high phosphate intake, and vitamin D deficiency 2
• Consider dietary phosphate restriction if hyperphosphatemia is present 2
• Use calcium supplements and/or native vitamin D (cholecalciferol/ergocalciferol) to correct deficiencies 2
• Avoid routine use of calcitriol or vitamin D analogs in CKD stages 3a-5 not on dialysis—this increases risk of adynamic bone disease and hypercalcemia 2
• Reserve calcimimetics (cinacalcet) for persistent secondary hyperparathyroidism, but use with caution due to hypocalcemia risk 3

Critical Monitoring Parameters

During Active Treatment of Secondary Hyperparathyroidism

• Check serum calcium and phosphorus monthly for the first 3 months, then every 3 months 2
• Measure PTH levels every 3 months for 6 months, then every 3-6 months 2

For CKD Patients Not on Active Treatment

• CKD G3a-G3b: calcium and phosphorus every 6-12 months 2
• CKD G4: every 3-6 months 2
• CKD G5: every 1-3 months 2

Common Pitfalls to Avoid

• Do not order parathyroid imaging before confirming biochemical diagnosis – imaging is for surgical planning, not diagnosis 1
• Do not assume normal PTH excludes primary hyperparathyroidism – inappropriately normal PTH in the presence of hypercalcemia confirms the diagnosis 1
• Do not supplement with vitamin D until hypercalcemia is resolved in primary hyperparathyroidism 1
• Do not use different PTH assay generations interchangeably – they vary by up to 47%; always use assay-specific reference values 1, 3
• Do not diagnose normocalcemic primary hyperparathyroidism without first correcting vitamin D deficiency and excluding CKD 2, 4

Special Considerations

PTH Measurement Technical Points

• Use EDTA plasma rather than serum—PTH is most stable in EDTA plasma at 4°C 1
• PTH reference values are 20% lower in vitamin D-replete individuals 1, 2
• Differences must exceed 54% to be clinically significant due to biological variation 1

Tertiary Hyperparathyroidism

• Occurs after longstanding secondary hyperparathyroidism, typically in end-stage renal disease patients after kidney transplant 3, 5, 6
• Characterized by hypercalcemia with elevated PTH—the hypertrophied parathyroid tissue continues to oversecrete PTH despite correction of the primary disorder 5, 6
• Primary treatment is surgical parathyroidectomy 3, 6