What is the significance of elevated Parathyroid Hormone (PTH) levels with normal calcium levels?

From the Guidelines

Elevated Parathyroid Hormone (PTH) levels with normal calcium levels, also known as normocalcemic hyperparathyroidism, is a significant finding that requires careful evaluation to determine the underlying cause, as it may be associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) 1. The clinical significance of this finding is multifaceted, involving various factors such as vitamin D deficiency, hypocalcemia, and hyperphosphatemia, which can contribute to the development of secondary hyperparathyroidism (SHPT) in patients with CKD 1.

Key Considerations

• The pathogenesis of SHPT is complex and driven by several factors, including vitamin D deficiency, hypocalcemia, and hyperphosphatemia, which can lead to abnormalities in bone mineralization and turnover 1.
• Modest increases in PTH levels may represent an appropriate adaptive response to decreasing kidney function due to phosphaturic effects and increasing bone resistance to PTH 1.
• The treatment of SHPT should be based on trends in PTH level, rather than a single elevated value, and should take into account modifiable risk factors such as high phosphate intake 1.

Evaluation and Management

• Initial workup should include comprehensive metabolic panel, 25-hydroxyvitamin D level, phosphorus, magnesium, and kidney function tests to identify underlying causes of elevated PTH levels.
• If vitamin D deficiency is identified, supplement with vitamin D3 1000-2000 IU daily and recheck levels in 2-3 months.
• For patients with normal vitamin D and no other identifiable causes, monitoring of calcium levels every 6-12 months is recommended, and referral to an endocrinologist may be necessary if the condition persists.

Clinical Implications

• Elevated PTH levels with normal calcium levels can be an early indicator of primary hyperparathyroidism or SHPT in patients with CKD, and prompt evaluation and management are essential to prevent long-term complications.
• The use of calcitriol and vitamin D analogues should be reserved for patients with CKD G4 to G5 with severe and progressive hyperparathyroidism, as the evidence for their effectiveness in improving patient-centered outcomes is limited 1.

From the FDA Drug Label

Approximately 60% of patients with mild (iPTH ≥ 300 to ≤ 500 pg/mL), 41% with moderate (iPTH > 500 to 800 pg/mL), and 11% with severe (iPTH > 800 pg/mL) secondary HPT achieved a mean iPTH value of ≤ 250 pg/mL.

The significance of elevated Parathyroid Hormone (PTH) levels with normal calcium levels is not directly addressed in the provided drug label. However, it can be inferred that elevated PTH levels are associated with secondary Hyperparathyroidism (HPT), and cinacalcet is used to decrease iPTH levels.

• Key points:
  • Elevated PTH levels are a concern in patients with secondary HPT.
  • Cinacalcet is used to decrease iPTH levels in these patients.
  • The goal of treatment is to achieve a mean iPTH value of ≤ 250 pg/mL. However, the label does not provide information on the significance of elevated PTH levels with normal calcium levels specifically. 2

From the Research

Significance of Elevated Parathyroid Hormone (PTH) Levels with Normal Calcium Levels

Elevated PTH levels with normal calcium levels can be indicative of several conditions, including:

• Normocalcemic primary hyperparathyroidism (PHPT) 3, 4, 5, 6
• Secondary hyperparathyroidism (SHPT) due to vitamin D deficiency, low calcium intake, impaired renal function, or other causes 3, 7, 5
• Renal calcium leak 3

Diagnostic Approach

The diagnostic approach for elevated PTH levels with normal calcium levels involves:

• Ruling out causes of SHPT, such as vitamin D deficiency, low calcium intake, and impaired renal function 3, 5
• Measuring 25-hydroxyvitamin D (25OHD) levels and replacing if indicated 5
• Using a calcium load test or thiazide challenge test to differentiate between SHPT and normocalcemic PHPT 3
• Applying a vitamin D-based, multidimensional nomogram to predict atypical primary hyperparathyroidism 6

Key Factors Affecting PTH Levels

Several factors can affect PTH levels, including:

• Calcium levels 7, 6
• 25-hydroxyvitamin D (25OHD) levels 7, 6
• Age 6
• Renal function 7

Clinical Implications

Elevated PTH levels with normal calcium levels can have significant clinical implications, including:

• Increased risk of osteoporosis and fractures 4
• Nephrolithiasis and nephrocalcinosis 4
• Cardiovascular disease 4