What does an elevated parathyroid hormone (PTH) level of 88.4 pg/mL with a normal serum calcium of 9.7 mg/dL indicate, and how should it be evaluated and managed?

Evaluation of Elevated PTH with Normal Calcium

This biochemical pattern most likely represents secondary hyperparathyroidism, and your immediate priority is to measure 25-hydroxyvitamin D and assess renal function to identify the underlying cause. 1

Diagnostic Interpretation

Your patient presents with:

• PTH 88.4 pg/mL (elevated, assuming normal range ~10-65 pg/mL)
• Calcium 9.7 mg/dL (normal, within 8.6-10.3 mg/dL range) 2

This combination—elevated PTH with normal calcium—is the hallmark of secondary hyperparathyroidism, not primary hyperparathyroidism. 2, 3 In primary hyperparathyroidism, the parathyroid glands autonomously secrete PTH despite elevated calcium; here, your patient's calcium is appropriately normal, indicating the PTH elevation is a physiologic response to an underlying stimulus. 2

Immediate Diagnostic Workup

Essential First-Line Tests

Order these laboratories immediately: 1, 2

• 25-hydroxyvitamin D – Vitamin D deficiency is the most common cause of secondary hyperparathyroidism and must be excluded first 2, 3
• Serum creatinine and eGFR – PTH concentrations rise when eGFR falls below 60 mL/min/1.73 m² (CKD stage 3 or higher) 1, 3
• Serum phosphorus – Typically normal or elevated in secondary hyperparathyroidism (versus low-normal in primary hyperparathyroidism) 2, 3
• Serum albumin – To confirm your calcium is truly normal (corrected calcium = measured calcium + 0.8 × [4 – serum albumin]) 1, 2

Second-Tier Tests (If Initial Workup Is Unrevealing)

• 1,25-dihydroxyvitamin D – Helps differentiate causes: both 25-OH and 1,25-(OH)₂ vitamin D are low in vitamin D deficiency; 1,25-(OH)₂ vitamin D is elevated in granulomatous disease despite low 25-OH vitamin D; 1,25-(OH)₂ vitamin D is typically low in CKD 2, 3
• 24-hour urine calcium or spot urine calcium/creatinine ratio – To assess calcium excretion and rule out hypercalciuria 2, 3
• Magnesium – Severe hypomagnesemia can impair PTH secretion and action

Most Likely Diagnoses (In Order of Probability)

1. Vitamin D Deficiency (Most Common)

Vitamin D deficiency is the most frequent cause of secondary hyperparathyroidism. 2, 3 The parathyroid glands appropriately increase PTH secretion to maintain normal serum calcium when vitamin D is insufficient.

• Diagnostic threshold: 25-hydroxyvitamin D <30 ng/mL warrants supplementation 1
• Target level: Aim for 25-hydroxyvitamin D >20 ng/mL (>50 nmol/L) to exclude vitamin D deficiency as the cause 2, 3
• Expected pattern: Low 25-OH vitamin D, elevated PTH, normal calcium, normal or low phosphorus 2

2. Chronic Kidney Disease (Second Most Common)

PTH begins to rise when eGFR drops below 60 mL/min/1.73 m². 1, 3 The kidneys lose their ability to convert 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D, and phosphorus retention stimulates PTH secretion.

• Screening threshold: Measure calcium, phosphorus, and PTH at least once when eGFR <45 mL/min/1.73 m² (CKD stage G3b-G5) 1
• Expected pattern: Elevated PTH, normal or low calcium, elevated phosphorus, low 1,25-dihydroxyvitamin D 2, 3

3. Dietary Calcium Deficiency (Less Common)

Inadequate dietary calcium intake (<1,000–1,200 mg/day for adults) can trigger secondary hyperparathyroidism. 2, 3 The parathyroid glands respond to low calcium absorption by increasing PTH.

• Assessment: Obtain a dietary history to estimate daily calcium intake 2, 3
• Expected pattern: Low dietary calcium, elevated PTH, normal serum calcium (maintained by bone resorption), low urine calcium 2

4. Normocalcemic Primary Hyperparathyroidism (Rare, Diagnosis of Exclusion)

Normocalcemic primary hyperparathyroidism (NPHPT) is defined by persistently elevated PTH with consistently normal albumin-corrected serum calcium, after exclusion of all secondary causes. 2 This is a diagnosis of exclusion and should only be considered after ruling out vitamin D deficiency, CKD, and dietary calcium deficiency.

• Diagnostic criteria: 2, 3
  • 25-hydroxyvitamin D >20 ng/mL (>50 nmol/L)
  • Adequate dietary calcium intake (≈1,000–1,200 mg/day)
  • eGFR ≥60 mL/min/1.73 m²
  • Persistently elevated PTH on repeat testing
  • Consistently normal calcium on multiple measurements

Management Algorithm

Step 1: If 25-Hydroxyvitamin D Is Low (<30 ng/mL)

Initiate vitamin D supplementation with ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3). 1, 2

• Dosing: Follow the K/DOQI guideline dosing schedule based on baseline 25-hydroxyvitamin D level 1
• Monitoring: Measure serum calcium and phosphorus at least every 3 months during supplementation 1, 2
• Discontinue vitamin D immediately if serum calcium exceeds 10.2 mg/dL 1, 2
• Recheck PTH after 3–6 months of vitamin D repletion – PTH should normalize if vitamin D deficiency was the sole cause 1, 2

Step 2: If eGFR Is <60 mL/min/1.73 m² (CKD Stage 3 or Higher)

This patient has CKD-related secondary hyperparathyroidism. 1, 3

• Monitoring frequency: 1, 3
  • CKD stage G3a-G3b (eGFR 30–59 mL/min/1.73 m²): Measure calcium, phosphorus, and PTH at least annually
  • CKD stage G4-G5 (eGFR <30 mL/min/1.73 m²): Measure calcium, phosphorus, and PTH at least twice per year
• Target PTH range for CKD stage 5 (dialysis): 150–300 pg/mL 2
• Avoid calcitriol or vitamin D analogs in CKD G3a-G5 not on dialysis – Reserve them only for severe and progressive hyperparathyroidism in CKD G4-G5 2
• Refer to nephrology for management of CKD-mineral bone disorder 1

Step 3: If Vitamin D Is Replete and eGFR Is Normal

Consider normocalcemic primary hyperparathyroidism (NPHPT) only after confirming: 2, 3

• 25-hydroxyvitamin D >20 ng/mL
• Adequate dietary calcium intake (≈1,000–1,200 mg/day)
• eGFR ≥60 mL/min/1.73 m²
• Persistently elevated PTH on repeat testing (at least 3 months apart)
• Consistently normal calcium on multiple measurements

If NPHPT is confirmed, refer to endocrinology and an experienced parathyroid surgeon for evaluation. 2, 3 Surgical indications for NPHPT include: 2, 3

• 24-hour urine calcium >400 mg/day (high risk for nephrocalcinosis and kidney stones)
• Osteoporosis (T-score ≤-2.5 at any site)
• Impaired kidney function (eGFR <60 mL/min/1.73 m²)
• History of nephrolithiasis or nephrocalcinosis
• Age <50 years
• Disabling neuropsychiatric symptoms (depression, cognitive impairment, "brain fog")

Critical Pitfalls to Avoid

• Do not diagnose primary hyperparathyroidism based on a single elevated PTH with normal calcium – This pattern is secondary hyperparathyroidism until proven otherwise 2, 3
• Do not order parathyroid imaging (ultrasound or sestamibi scan) before confirming the biochemical diagnosis – Imaging is for surgical planning, not diagnosis 2, 3
• Do not supplement with vitamin D until you measure baseline 25-hydroxyvitamin D – You need the baseline value to guide dosing and monitor response 1, 2
• Do not use calcitriol (active vitamin D) in this setting – Calcitriol increases intestinal calcium absorption and can cause hypercalcemia; use ergocalciferol or cholecalciferol instead 1, 2
• Be aware that PTH assays vary significantly between laboratories – Use assay-specific reference ranges and always use the same laboratory for serial measurements 2, 3
• Collect blood for PTH measurement in EDTA tubes – PTH is most stable in EDTA plasma at 4°C 2, 3

PTH Measurement Considerations

PTH assays differ markedly between generations—differences of up to 47% have been reported—so always use assay-specific reference values. 2, 3 Second-generation "intact PTH" assays (the current standard) detect both biologically active PTH and inactive C-terminal fragments; in CKD, these fragments accumulate and can overestimate true PTH activity. 2, 3

Biological variation of PTH is substantial: ~20% in healthy individuals and up to 30% in hemodialysis patients; a change greater than 54% is required to be clinically meaningful in healthy people. 2, 3

PTH concentrations are influenced by: 2, 3

• Age – PTH increases with age due to declining eGFR
• Race – PTH levels are higher on average in Black individuals
• BMI – Higher BMI is positively correlated with PTH
• Vitamin D status – PTH reference values are 20% lower in vitamin D-replete individuals