What does an elevated Parathyroid Hormone (PTH) level mean?

What Does an Elevated PTH Mean?

An elevated parathyroid hormone (PTH) level most commonly indicates primary hyperparathyroidism, secondary hyperparathyroidism due to vitamin D deficiency or chronic kidney disease, or tertiary hyperparathyroidism in patients with longstanding kidney disease. 1

Primary Causes of Elevated PTH

• Primary Hyperparathyroidism (PHPT): Characterized by autonomous overproduction of PTH from abnormal parathyroid tissue (usually adenoma or hyperplasia), leading to hypercalcemia with elevated or inappropriately normal PTH 1, 2

  • Normocalcemic variant: Elevated PTH with normal calcium levels, still at risk for complications of classic PHPT 1
  • May lead to osteoporosis, kidney stones, and hypercalciuria 2

• Secondary Hyperparathyroidism (SHPT): Compensatory increase in PTH due to:

  • Vitamin D deficiency (most common cause) 1
  • Chronic kidney disease (CKD) - declining kidney function disturbs calcium and phosphate homeostasis 1
  • Chronic intestinal malabsorption, hepatobiliary disease, or tubular acidosis 3

• Tertiary Hyperparathyroidism: Occurs when hyperplastic parathyroid glands become autonomous after longstanding secondary hyperparathyroidism, often in patients after kidney transplantation 1, 4

Factors That Can Influence PTH Levels

• Biological factors:

  • Race: PTH levels are higher in Black individuals compared to White individuals 1
  • Age: PTH increases with increasing age (due to declining kidney function) 1
  • BMI: Higher PTH concentrations in obese patients 1
  • Vitamin D status: Deficiency increases PTH levels 1

• Preanalytical factors:

  • Sample type: PTH is more stable in EDTA plasma than serum 1
  • Sampling site: Higher PTH concentrations in central blood compared to peripheral blood 1
  • Sampling time: PTH has a circadian rhythm 1

Clinical Implications of Elevated PTH

• Bone effects:

  • Increased bone resorption leading to osteopenia or osteitis fibrosa cystica 3
  • Higher risk of fractures, especially in untreated cases 2

• Renal effects:

  • Increased risk of kidney stones and nephrocalcinosis 2
  • Hypercalciuria 3

• Neuromuscular and psychiatric effects:

  • Fatigue, weakness, and cognitive changes may occur 5
  • Decreased neuromuscular irritability and deep tendon reflexes 5

• Gastrointestinal effects:

  • Anorexia, nausea, vomiting, and constipation (especially with calcium >12 mg/dL) 3

Diagnostic Considerations

• Calcium levels should always be measured alongside PTH:

  • Elevated calcium + elevated PTH: Suggests primary hyperparathyroidism 1
  • Normal calcium + elevated PTH: Consider normocalcemic PHPT, vitamin D deficiency, or early CKD 1
  • Low calcium + elevated PTH: Suggests secondary hyperparathyroidism 3

• Assay considerations:

  • Different PTH assay generations may yield different results 1
  • Use assay-specific reference values when interpreting results 1
  • Biotin supplements can interfere with some PTH assays 1

• Additional testing to consider:

  • Vitamin D levels (25-OH vitamin D)
  • Kidney function tests (creatinine, GFR)
  • Phosphorus levels
  • Urinary calcium excretion 2

Common Pitfalls in PTH Interpretation

• Failure to consider vitamin D status: Vitamin D deficiency is a common cause of secondary hyperparathyroidism and can lead to misdiagnosis if not assessed 1

• Not accounting for biological variation: PTH has substantial biological variation (~20% in healthy people, up to 30% in hemodialysis patients) 1

• Ignoring kidney function: Declining kidney function can lead to elevated PTH, even with mild reductions in GFR 1

• Using inappropriate reference ranges: Reference values should account for vitamin D status, BMI, race, age, and the specific assay used 1