How do you interpret calcium and Parathyroid Hormone (PTH) levels?

Interpretation of Calcium and Parathyroid Hormone (PTH) Levels

The interpretation of calcium and PTH levels should follow a structured approach focusing on their relationship, as abnormalities in these parameters indicate specific disorders of mineral metabolism that impact morbidity and mortality.

Normal Ranges and Relationship

• Serum calcium normal range is typically 8.4-9.5 mg/dL (2.10-2.37 mmol/L), with free (ionized) calcium ranging from 4.65-5.28 mg/dL (1.16-1.32 mmol/L) 1
• Normal PTH levels vary by assay type, but generally range between 10-65 pg/mL, with higher upper limits in older adults 1
• PTH and calcium have an inverse relationship - when calcium decreases, PTH increases to restore normal calcium levels 1

Key Patterns and Their Interpretation

Pattern 1: High Calcium, High PTH

• Suggests primary hyperparathyroidism - typically caused by parathyroid adenoma, hyperplasia, or rarely carcinoma 1
• Calcium >10.2 mg/dL with inappropriately normal or elevated PTH 2
• Parathyroid scintigraphy is positive in nearly 100% of cases when calcium >12 mg/dL and in 62% when calcium is 11-12 mg/dL 3

Pattern 2: Normal Calcium, High PTH

• Consider normocalcemic hyperparathyroidism after excluding:
  • Vitamin D deficiency (most common cause) 1, 4
  • Chronic kidney disease (CKD) 1
  • Medications (thiazides, lithium) 5
  • Malabsorption syndromes 4
• Calculate adjusted calcium if albumin is abnormal, as total calcium may appear normal despite abnormal free calcium 1
• PTH >120 pg/mL with calcium 9.9-11 mg/dL has 78% positive parathyroid scintigraphy, suggesting subclinical primary hyperparathyroidism 3

Pattern 3: Low Calcium, High PTH

• Indicates secondary hyperparathyroidism - appropriate physiologic response to hypocalcemia 1
• Common causes:
  • Vitamin D deficiency 1
  • Chronic kidney disease (CKD) 1
  • Malabsorption (e.g., celiac disease, bariatric surgery) 1
  • Medications (e.g., bisphosphonates, denosumab) 5
• In CKD, target ranges for intact PTH vary by stage; for CKD G5D, the lowest mortality risk is observed with PTH 300-599 pg/mL 6

Pattern 4: High Calcium, Low/Normal PTH

• Suggests non-parathyroid hypercalcemia 1
• Causes include:
  • Malignancy (PTH-related protein)
  • Granulomatous diseases (sarcoidosis)
  • Vitamin D intoxication
  • Thyrotoxicosis
  • Medications (thiazides, lithium, vitamin A excess)

Pattern 5: Low Calcium, Low/Normal PTH

• Indicates hypoparathyroidism or pseudohypoparathyroidism 1
• Causes include:
  • Post-surgical (thyroidectomy, parathyroidectomy) 1
  • Autoimmune
  • Genetic disorders
  • Magnesium disorders (both deficiency and excess)

Special Considerations

Chronic Kidney Disease

• In CKD G3a-G5 not on dialysis, evaluate progressively rising or persistently elevated PTH for modifiable factors: hyperphosphatemia, hypocalcemia, high phosphate intake, vitamin D deficiency 1
• In CKD G5D, the PTH/mortality relationship is U-shaped with lowest risk at PTH 300-599 pg/mL 6
• Mortality is nearly 20% higher with serum calcium >9.6 mg/dL versus 8.4-9.6 mg/dL in peritoneal dialysis patients 6
• For patients with elevated PTH requiring treatment, options include calcimimetics, calcitriol, or vitamin D analogs 1

Post-Bariatric Surgery

• Regular monitoring of calcium, vitamin D, and PTH is recommended after bariatric surgery 1
• PTH >65 pg/mL may indicate calcium or vitamin D deficiency even with normal serum calcium 1
• Normal calcium levels can be maintained despite inadequate intake through compensatory mechanisms (bone resorption, decreased renal excretion) 1

Assay Considerations

• Different PTH assay generations (second vs. third) may yield different results 1
• Biological variation of PTH is substantial (20% in healthy people, up to 30% in hemodialysis patients) 1
• PTH levels are affected by race, age, BMI, and vitamin D status 1
• Guidelines should avoid stating absolute cutoff values without specifying assay type 1

Clinical Approach to Abnormal Results

1. Confirm results - repeat measurements if values are unexpected 1
2. Check vitamin D status - 25(OH)D should be measured and deficiency corrected 1, 4
3. Assess renal function - calculate eGFR to determine if CKD is present 1
4. Review medications - identify drugs that affect calcium/PTH 5
5. Calculate corrected calcium if albumin is abnormal 1
6. Evaluate for symptoms - bone pain, fractures, kidney stones, neuromuscular symptoms 1, 2
7. Consider additional testing based on suspected diagnosis:
   • 24-hour urinary calcium
   • Bone mineral density
   • Phosphate levels
   • Alkaline phosphatase 1

Remember that the interpretation of calcium and PTH must consider the clinical context, medication use, kidney function, and vitamin D status for accurate diagnosis and appropriate management decisions.