In an 86‑year‑old patient with elevated parathyroid hormone and normal serum calcium, phosphorus, and 25‑hydroxy vitamin D levels, what is the appropriate next step in evaluation and management?

Management of Elevated PTH with Normal Calcium in an 86-Year-Old Patient

In an 86-year-old patient with elevated PTH and normal calcium, phosphorus, and vitamin D levels, the immediate next step is to assess kidney function (eGFR) to distinguish between normocalcemic primary hyperparathyroidism and CKD-related secondary hyperparathyroidism, as PTH rises early in chronic kidney disease even before calcium or phosphorus abnormalities appear. 1

Initial Diagnostic Algorithm

Step 1: Assess Kidney Function

• Measure serum creatinine and calculate eGFR immediately, as this is the single most critical test to guide all subsequent management decisions. 1
• PTH begins to rise when GFR falls below 60 mL/min/1.73 m², often before other mineral abnormalities become apparent. 2
• In elderly patients, age-related decline in GFR is common and represents the most frequent cause of elevated PTH with normal calcium. 3

Step 2: Verify Vitamin D Status Despite "Normal" Reported Levels

• Confirm that 25-OH vitamin D is truly ≥30 ng/mL, as levels between 20-30 ng/mL are insufficient and will drive secondary hyperparathyroidism. 1
• Vitamin D deficiency (<30 ng/mL) is the most common and most frequently missed reversible cause of elevated PTH with normal calcium. 1
• PTH reference values are 20% lower in vitamin D-replete individuals compared to those with unknown vitamin D status. 3

Step 3: Measure 24-Hour Urinary Calcium

• Obtain 24-hour urinary calcium excretion to distinguish normocalcemic primary hyperparathyroidism (often elevated urinary calcium >250-300 mg/day) from secondary hyperparathyroidism (typically low-normal urinary calcium). 4, 5
• Elevated urinary calcium (>300 mg/24hr) in the setting of normal serum calcium strongly suggests normocalcemic primary hyperparathyroidism and is an indication for parathyroidectomy. 4

Interpretation Based on eGFR Results

If eGFR ≥60 mL/min/1.73 m² (Normal Kidney Function)

This scenario suggests normocalcemic primary hyperparathyroidism (NPHPT) after excluding secondary causes. 5

Diagnostic Confirmation for NPHPT:

• Verify PTH elevation is persistent by repeating measurement in 3 months, as biological variation of PTH is substantial (~20% in healthy individuals). 3, 1
• Confirm 25-OH vitamin D ≥30 ng/mL and adequate dietary calcium intake (1000-1200 mg/day). 1, 5
• Exclude medications that elevate PTH: thiazide diuretics, lithium, bisphosphonates, or denosumab. 4, 5

Clinical Significance of NPHPT:

• NPHPT is not a benign entity—despite normal calcium, it carries comparable risk to hypercalcemic primary hyperparathyroidism. 6, 7
• Occult renal calcifications occur in 26.5% of NPHPT patients and correlate with higher PTH levels. 4
• Osteoporosis is present in 57% of NPHPT patients at diagnosis, without the typical preferential cortical bone loss seen in hypercalcemic PHPT. 6
• 40% of NPHPT patients develop progression to hypercalcemia, kidney stones, fractures, or >10% bone loss over 3 years. 6

Management of NPHPT:

• Refer to endocrinology and an experienced high-volume parathyroid surgeon for evaluation, as surgical outcomes are significantly better with specialized expertise. 1
• Obtain renal ultrasound to screen for occult nephrocalcinosis, which is common and may be asymptomatic. 4
• Measure bone mineral density (DXA scan) at spine, hip, and distal radius to assess for osteoporosis. 6

Surgical indications in NPHPT include: 1, 6

• 24-hour urinary calcium >300 mg/day (risk of progressive nephrocalcinosis)
• Osteoporosis (T-score ≤-2.5 at any site)
• Age <50 years
• Patient preference for definitive treatment
• Symptomatic disease (neurocognitive symptoms, kidney stones, fractures)

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

This represents CKD-related secondary hyperparathyroidism, which requires a fundamentally different management approach. 2

Management Algorithm for CKD Stage 3:

• Do NOT initiate active vitamin D therapy (calcitriol) at this stage, as the target PTH range for CKD stage 3 is not well-defined and aggressive suppression risks adynamic bone disease. 2
• Ensure 25-OH vitamin D ≥30 ng/mL using cholecalciferol or ergocalciferol supplementation. 1, 2
• Maintain dietary phosphorus restriction to 800-1000 mg/day if phosphorus trends toward upper normal range. 2
• Target PTH levels: 35-70 pg/mL for CKD stage 3a; 70-110 pg/mL for CKD stage 3b. 2

Monitoring Schedule for CKD Stage 3:

• Measure calcium and phosphorus every 6-12 months for CKD G3a-G3b. 1
• Measure PTH every 12 months to track trends. 2
• Repeat 25-OH vitamin D annually once replete. 2

If eGFR 15-29 mL/min/1.73 m² (CKD Stage 4)

More intensive monitoring and potential intervention are required at this stage. 2

• Target PTH: 70-110 pg/mL (not normal range, as this causes adynamic bone disease). 2
• Measure calcium and phosphorus every 3-6 months. 1
• Measure PTH every 3 months. 2
• Consider active vitamin D therapy (calcitriol) only if PTH continues rising despite vitamin D repletion AND phosphorus remains <4.6 mg/dL. 2

If eGFR <15 mL/min/1.73 m² (CKD Stage 5)

This requires nephrology co-management and specialized CKD-mineral bone disease protocols. 2

• Target PTH: 150-300 pg/mL for dialysis patients. 2
• Measure calcium and phosphorus every 1-3 months. 1
• Aggressive PTH suppression to normal range (<65 pg/mL) causes adynamic bone disease with increased fracture risk. 2

Critical Pitfalls to Avoid

Common Diagnostic Errors:

• Assuming all elevated PTH with normal calcium is "secondary hyperparathyroidism" without excluding normocalcemic primary hyperparathyroidism through 24-hour urinary calcium and imaging. 5
• Accepting 25-OH vitamin D levels of 20-30 ng/mL as "normal" when ≥30 ng/mL is required to exclude vitamin D deficiency as a cause. 1, 5
• Ordering parathyroid imaging before confirming biochemical diagnosis—imaging is for surgical planning, not diagnosis. 8
• Using a single PTH measurement rather than confirming persistent elevation, given the 20% biological variation. 3

Age-Specific Considerations for This 86-Year-Old Patient:

• PTH increases with age due to steady decline in GFR, making age-related CKD the most likely diagnosis. 3
• PTH concentrations are influenced by age, and reference values should account for this. 3
• However, age alone does not exclude normocalcemic primary hyperparathyroidism, which can present at any age and requires the same systematic evaluation. 6, 7

Treatment Pitfalls:

• Starting calcitriol when phosphorus is elevated worsens vascular calcification and increases calcium-phosphate product. 2
• Targeting normal PTH levels in CKD patients causes adynamic bone disease with low bone turnover and increased fracture risk. 2
• Ignoring alkaline phosphatase, which adds predictive value when interpreting PTH levels for assessing bone turnover. 2

Practical Next Steps Summary

For this 86-year-old patient, order the following tests immediately: 1, 2

1. Serum creatinine and eGFR calculation (most critical)
2. Repeat 25-OH vitamin D to verify ≥30 ng/mL
3. 24-hour urinary calcium excretion
4. Repeat PTH in 3 months to confirm persistent elevation
5. Renal ultrasound to screen for nephrocalcinosis
6. Bone density scan (DXA) at spine, hip, and distal radius

The eGFR result will determine whether this patient has:

• Normocalcemic primary hyperparathyroidism (eGFR ≥60) → endocrine/surgical referral
• CKD-related secondary hyperparathyroidism (eGFR <60) → nephrology co-management and conservative treatment

Do not initiate any vitamin D therapy until the diagnostic workup is complete and the underlying etiology is established. 2, 5