From the Guidelines
Elevated parathyroid hormone (PTH) levels with normal calcium and vitamin D levels are most commonly caused by normocalcemic hyperparathyroidism or secondary hyperparathyroidism due to early kidney disease, as supported by the most recent guideline update 1. The condition occurs when the parathyroid glands overproduce PTH despite normal calcium levels, often representing an early stage of primary hyperparathyroidism where the body can still maintain normal calcium homeostasis. Early chronic kidney disease can elevate PTH before calcium or vitamin D levels become abnormal, as the kidneys begin to lose their ability to excrete phosphate, triggering PTH secretion, as noted in the study on chronic kidney disease-mineral and bone disorder 1. Other potential causes include:
- Vitamin D insufficiency (levels that are technically normal but suboptimal)
- Certain medications like lithium or thiazide diuretics
- Magnesium deficiency
- PTH resistance in tissues Evaluation should include comprehensive metabolic testing, including:
- Renal function
- Ionized calcium
- Phosphorus
- Magnesium
- 24-hour urine calcium If no clear cause is found, monitoring PTH and calcium levels every 6-12 months is recommended, as some patients will eventually develop overt hyperparathyroidism requiring treatment 1. The elevated PTH occurs because the parathyroid glands are either autonomously secreting excess hormone or responding appropriately to subtle metabolic changes that standard laboratory tests don't fully capture, highlighting the importance of regular monitoring and assessment of these patients.
From the Research
Causes of Elevated Parathyroid Hormone (PTH) with Normal Calcium and Vitamin D Levels
Elevated Parathyroid Hormone (PTH) levels with normal calcium and vitamin D levels can be caused by several factors, including:
- Low free 25-hydroxyvitamin D levels, as seen in a study published in 2020 2, which found that subjects with normocalcemic primary hyperparathyroidism had lower free 25-hydroxyvitamin D levels compared to healthy controls.
- Renal dysfunction, as elevated PTH levels are often associated with renal disease, and can be seen even in patients with normal calcium and vitamin D levels 3.
- Vitamin D deficiency or insufficiency, as vitamin D plays a crucial role in regulating PTH levels, and deficiency or insufficiency can lead to elevated PTH levels 4, 5.
- Other factors, such as genetic disorders, certain medications, or other medical conditions, which can also contribute to elevated PTH levels with normal calcium and vitamin D levels.
Biochemical Parameters and PTH Levels
Studies have shown that adjusting vitamin D doses can impact PTH levels, with some studies finding that reducing or increasing vitamin D doses can lower PTH levels 6. Additionally, elevated PTH levels have been associated with increased cardiovascular disease risk, independent of vitamin D status and renal function 3.
Treatment and Management
Treatment and management of elevated PTH levels with normal calcium and vitamin D levels may involve addressing underlying causes, such as vitamin D deficiency or renal dysfunction. Aggressive oral calcium and vitamin D supplementation may also be effective in decreasing endogenous PTH levels and improving hypophosphatemia in certain patients 5. However, more research is needed to fully understand the causes and optimal treatment strategies for elevated PTH levels with normal calcium and vitamin D levels.